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Sample records for advanced cancer therapy

  1. [PVB therapy for advanced testicular cancer].

    PubMed

    Nakao, M; Nakagawa, S; Toyoda, K; Nukui, M; Takada, H; Ebisui, K; Sugimoto, K; Watanabe, H; Maegawa, M; Miyakoda, K

    1989-11-01

    Twelve cases of advanced testicular cancer, including 5 cases of seminoma, 3 cases of teratocarcinoma, 1 case of yolk sac tumor, 1 case of embryonal carcinoma and 2 cases of mixed cell type, were treated with cisplatin-vinblastine-bleomycin (PVB) therapy. Among them, 10 cases had measurable metastatic lesions and the objective response rate was 80%. Three cases showed complete response. Ten cases showed nonexistent disease after PVB therapy and salvage operation. Though PVB therapy was useful for the treatment of advanced testicular cancer, a few cases having poor prognostic factors showed no response to the therapy.

  2. Photodynamic Cancer Therapy - Recent Advances

    SciTech Connect

    Abrahamse, Heidi

    2011-09-22

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  3. Preoperative therapy in locally advanced esophageal cancer

    PubMed Central

    Garg, Pankaj Kumar; Sharma, Jyoti; Jakhetiya, Ashish; Goel, Aakanksha; Gaur, Manish Kumar

    2016-01-01

    Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

  4. Biologic therapies for advanced pancreatic cancer.

    PubMed

    He, Aiwu Ruth; Lindenberg, Andreas Peter; Marshall, John Lindsay

    2008-08-01

    Patients with metastatic pancreatic cancer have poor prognosis and short survival due to lack of effective therapy and aggressiveness of the disease. Pancreatic cancer has widespread chromosomal instability, including a high rate of translocations and deletions. Upregulated EGF signaling and mutation of K-RAS are found in most pancreatic cancers. Therefore, inhibitors that target EGF receptor, K-RAS, RAF, MEK, mTOR, VEGF and PDGF, for example, have been evaluated in patients with pancreatic cancer. Although significant activities of these inhibitors have not been observed in the majority of pancreatic cancer patients, an enormous amount of experience and knowledge has been obtained from recent clinical trials. With a better inhibitor or combination of inhibitors, and improvement in the selection of patients for available inhibitors, better therapy for pancreatic cancer is on the horizon.

  5. Molecular targeted therapy for advanced gastric cancer

    PubMed Central

    2013-01-01

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies. PMID:23525404

  6. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  7. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Cancer.gov

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  8. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  9. Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer.

    PubMed

    Chadha, Awalpreet S; Khoo, Allison; Aliru, Maureen L; Arora, Harpreet K; Gunther, Jillian R; Krishnan, Sunil

    2016-10-01

    The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death. Technical advances have allowed for the safe delivery of dose-escalated radiation therapy, which can then be combined with chemotherapy, targeted agents, immunotherapy, and nanoparticulate drug delivery techniques to produce novel and improved synergistic effects. Here we discuss recent advances and future directions for multimodality therapy in pancreatic cancer. PMID:27619253

  10. Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer.

    PubMed

    Chadha, Awalpreet S; Khoo, Allison; Aliru, Maureen L; Arora, Harpreet K; Gunther, Jillian R; Krishnan, Sunil

    2016-10-01

    The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death. Technical advances have allowed for the safe delivery of dose-escalated radiation therapy, which can then be combined with chemotherapy, targeted agents, immunotherapy, and nanoparticulate drug delivery techniques to produce novel and improved synergistic effects. Here we discuss recent advances and future directions for multimodality therapy in pancreatic cancer.

  11. Proton beam therapy for locally advanced lung cancer: A review

    PubMed Central

    Schild, Steven E; Rule, William G; Ashman, Jonathan B; Vora, Sujay A; Keole, Sameer; Anand, Aman; Liu, Wei; Bues, Martin

    2014-01-01

    Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer. PMID:25302161

  12. Glucose Addiction in Cancer Therapy: Advances and Drawbacks.

    PubMed

    Granja, Sara; Pinheiro, Céline; Reis, Rui Manuel; Martinho, Olga; Baltazar, Fátima

    2015-01-01

    While normal differentiated cells primarily use mitochondrial respiration to generate the required energy for cellular processes, most cancer cells rely on glycolysis, even in sufficient oxygen conditions. This phenomenon is known as the "Warburg effect" or aerobic glycolysis and the metabolic reprogramming of cancer cells towards this altered energy metabolism is currently recognized as one of the "hallmarks of cancer". Aerobic glycolysis underlies the rapid growth of tumor cells, with high rates of glucose consumption and lactic acid production, leading to cellular acidosis. Metabolic reprogramming renders cancer cells dependent on specific metabolic enzymes or pathways that could be exploited in cancer therapy. The development of treatments that target tumor glucose metabolism is receiving renewed attention, with several drugs targeting metabolic pathways currently in clinical trials. The search for suitable targets, however, is limited by the high plasticity of the metabolic network that can induce compensatory routes. Deregulated glucose metabolism is a prominent feature associated with resistance to classical chemotherapy or oncogene-targeted therapies, strengthening the clinical potential of combining these therapies with glycolysis inhibitors. The aim of this review is to compare the advances of different therapeutic strategies targeting the glucose "addiction" of tumor cells, highlighting their potential as effective weapons against cancer. We further discuss recent evidence for the involvement of glucose metabolism as a compensatory response to the use of drugs that target different signaling pathways, where the combination with glycolysis inhibitors could prove extraordinarily useful. PMID:26504932

  13. FOREWORD: Conference on Advanced Metrology for Cancer Therapy 2011 Conference on Advanced Metrology for Cancer Therapy 2011

    NASA Astrophysics Data System (ADS)

    Ankerhold, Ulrike

    2012-10-01

    Although physical treatments play a central role in cancer therapy, SI-traceable metrology has only been established for some of them. Several forms of treatment currently used (particularly intensity-modulated radiation therapy (IMRT), hadron therapy, high-intensity therapeutic ultrasound (HITU) and brachytherapy) suffer from the limited metrological support, which restricts the success of these techniques. Recognizing this deficit, the European Union identified metrology for health as one of the first four Targeted Programmes in the framework of the European Metrology Research Programme (EMRP) running from 2008 to 2011. This programme included two EMRP projects addressing metrology for cancer therapy: project T2.J06 dealing with brachytherapy project T2.J07 dealing with external beam cancer therapy using ionizing radiation and high-intensity therapeutic ultrasound. Primary measurement standards applicable to modern treatment conditions were developed under both projects, together with measurement techniques which are meant as a basis for future protocols for dosimetry, treatment planning and monitoring. In order to provide a platform for the presentation of current developments in clinical measurement techniques for cancer therapy, together with the achievements of both projects, an international Conference on Advanced Metrology for Cancer Therapy (CAMCT) was held from 29 November to 1 December 2011 at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The main sessions of the conference: Primary and secondary standards of absorbed dose to water for IMRT and brachytherapy, 3D dose distributions and treatment planning for IMRT and brachytherapy, Hadron therapy (protons and carbon ions), High-intensity therapeutic ultrasound (HITU), were geared to the main foci of the projects. Metrologists and medical physicists from countries all over the world attended the conference and made it into a forum for the exchange of information and expertise

  14. Integrative and complementary therapies for patients with advanced cancer.

    PubMed

    Marchand, Lucille

    2014-07-01

    In integrative medicine, well-being is emphasized, and in palliative care, quality of life (QOL) is a similar concept or goal. Both can occur despite advanced cancer. Integrative medicine serves to combine the best of alternative, complementary and conventional therapies to optimize well-being and QOL, whether or not a person is at the end of their life. When integrative medicine is combined with palliative care modalities, the toolbox to provide symptom control and well-being or QOL is increased or broadened. Palliative care and integrative medicine are best provided early in the trajectory of illness such as cancer, and increase in amount as the illness progresses toward end of life. In cancer care, symptoms of the cancer, as well as symptoms produced by cancer therapies, are addressed with conventional and integrative therapies. Goals of care change as the disease progresses, and a patient's unique situation creates a different balance of integrative and conventional therapies. Integrative therapies such as music, aromatherapy, and massage might appeal to more patients than more specific, less common integrative therapies that might be more expensive, or seem more unusual such as Ayurvedic medicine and energy modalities. Each person may be drawn to different integrative modalities depending on factors such as cultural traditions, beliefs, lifestyle, internet information, advice from family and friends, books, etc. This review focuses on how integrative and complementary modalities can be included in comprehensive palliative care for patients with advanced malignancies. Nutrition and movement, often neglected in conventional treatment strategies, will also be included in the larger context of integrative and palliative modalities. Both conventional and integrative modalities in palliative care help patients live with empowerment, hope, and well-being no matter how long their lives last. A comprehensive review of all integrative and complementary therapies is

  15. Targeted Therapies in Breast Cancer: Implications for Advanced Oncology Practice

    PubMed Central

    Bourdeanu, Laura; Luu, Thehan

    2014-01-01

    The systemic therapeutic management of breast cancer has undergone significant transformation in the past decade. Without targeted therapies, conventional treatment with cytotoxic agents has reached the limit of its potential in terms of patient survival for most types of cancer. Enhanced understanding of the pathogenesis of tumor cell growth and metastasis has led to the identification of signaling growth pathways as targets for these directed therapies. Novel therapies targeted to HER2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), poly(ADP ribose) polymerase (PARP), mammalian target of rapamycin (mTOR), histone deacetylase (HDAC), the heat shock protein, and cyclin-dependent kinase (CDK) inhibitors have been developed and have demonstrated some efficacy in breast cancer. Recognition and management of the toxicities associated with targeted therapies is imperative. This review will describe the clinical development and utilization of targeted therapies currently in use or in clinical trials, with a focus on considerations for the oncology advanced practitioner. PMID:26110069

  16. Advances in stimuli responsive nanobiomaterials for cancer therapy.

    PubMed

    Sampathkumar, Kaarunya; Arulkumar, Shylaja; Ramalingam, Murugan

    2014-03-01

    Cancer has become one of the major reasons for disease mortality with drastic increase of death rate in recent years. The reason for most of these deaths is due to the inefficacy and failure of the current methods of treatments or due to the unavailability of treatment options. Even after extensive research that has been carried out in the field, there is no gold standard in cancer therapy. With the advancement of the field of nanomedicine and materials science, many research works are being aimed at developing micro and nanocarriers for site-specific delivery of anticancer drugs. As a further advancement in the field, smart carriers, based on nanobiomaterials, which respond to various external and internal stimuli and act locally are being developed to improve the efficacy of current treatments. These smart nanobiomaterials act as carriers for not only anticancer drugs but also for gene and other biomolecules. Keeping the importance and advancement of smart carrier anticancer drug delivery system (AcDDS) in view, this review focuses on stimuli responsive nanobiomaterials that are currently being studied for cancer therapy. PMID:24730233

  17. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  18. Recent Advances in Molecular Image-Guided Cancer Radionuclide Therapy.

    PubMed

    Gao, Duo; Sun, Xianlei; Gao, Liquan; Liu, Zhaofei

    2015-01-01

    Cancer-targeted radionuclide therapy is a promising approach for the treatment of a wide variety of malignancies, especially those resistant to conventional therapies. However, to improve the use of targeted radionuclide therapy for the management of cancer patients, the in vivo behaviors, dosimetry, and efficacy of radiotherapeutic agents need to be well characterized and monitored. Molecular imaging, which is a powerful tool for the noninvasive characterization and quantification of biological processes in living subjects at the cellular and molecular levels, plays an important role in the guidance of cancer radionuclide therapy. In this review, we introduce the radiotherapeutics for cancer-targeted therapy and summarize the most recent evidence supporting the use of molecular imaging to guide cancer radionuclide therapy.

  19. The progress of targeted therapy in advanced gastric cancer

    PubMed Central

    2013-01-01

    Although palliative chemotherapy has been shown to prolong survival and improve quality of life, the survival of advanced gastric cancer (AGC) patients remains poor. With the advent of targeted therapy, many molecular targeted agents have been evaluated in clinical studies. Trastuzumab, an anti-HER2 monoclonal antibody, has shown activity against HER2-positive AGC and becomes the first targeted agent approved in AGC. Drugs that target epidermal growth factor receptor, including monoclonal antibody and tyrosine kinase inhibitor, do not bring survival benefit to patients with AGC. Additionally, vascular endothelial growth factor inhibitors are also under investigation. Ramucirumab has shown promising result. Other targeted agents are in preclinical or early clinical development, such as mammalian target of rapamycinm inhibitors and c-MET inhibitors. PMID:24330856

  20. Present and future evolution of advanced breast cancer therapy

    PubMed Central

    2010-01-01

    Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents. PMID:21050422

  1. Advances in biodegradable nanomaterials for photothermal therapy of cancer

    PubMed Central

    He, Chao-Feng; Wang, Shun-Hao; Yu, Ying-Jie; Shen, He-Yun; Zhao, Yan; Gao, Hui-Ling; Wang, Hai; Li, Lin-Lin; Liu, Hui-Yu

    2016-01-01

    Photothermal cancer therapy is an alternative to chemotherapy, radiotherapy, and surgery. With the development of nanophotothermal agents, this therapy holds immense potential in clinical translation. However, the toxicity issues derived from the fact that nanomaterials are trapped and retained in the reticuloendothelial systems limit their biomedical application. Developing biodegradable photothermal agents is the most practical route to address these concerns. In addition to the physicochemical properties of nanomaterials, various internal and external stimuli play key roles on nanomaterials uptake, transport, and clearance. In this review, we summarized novel nanoplatforms for photothermal therapy; these nanoplatforms can elicit stimuli-triggered degradation. We focused on the recent innovative designs endowed with biodegradable photothermal agents under different stimuli, including enzyme, pH, and near-infrared (NIR) laser. PMID:27807498

  2. Intermittent hormone therapy versus continuous hormone therapy for locally advanced prostate cancer: a meta-analysis.

    PubMed

    Dong, ZhiLong; Wang, Hanzhang; Xu, MengMeng; Li, Yang; Hou, MingLi; Wei, YanLing; Liu, Xingchen; Wang, ZhiPing; Xie, XiaoDong

    2015-01-01

    Few randomized studies have compared intermittent hormone therapy (IHT) with continuous hormone therapy (CHT) for the treatment of locally advanced prostate cancer (PCa). Here, we report the results of a meta-analysis of a randomized controlled trial, evaluating the effectiveness of IHT versus CHT for patients with locally advanced PCa. Types of intervention were IHT versus CHT. The primary endpoint of this study is overall mortality and the secondary endpoints are any progression of disease, quality of life (QOL) and adverse effects between two groups. Six randomized controlled trials totaling 2996 patients were included. Results are as follows: after hormone therapy, patients undergoing IHT demonstrated no significant difference from those undergoing CHT in terms of the overall mortality (OR = 1.0, 95% CI [0.86, 1.17]) and disease progression (OR = 1.16, 95% CI [0.86, 1.57]). Men treated with IHT also reported better QOL, fewer adverse effects and considerable economic benefit for the individual and the community. With no difference in overall mortality and incidence of progression, current clinical studies confirm that both therapeutic methods were safe and effective. However, our study also takes into account QOL. When these secondary measures are considered, IHT may be a better option over CHT as patients report a more affordable treatment with improved QOL and fewer adverse effects.

  3. Recent advances of sonodynamic therapy in cancer treatment

    PubMed Central

    Wan, Guo-Yun; Liu, Yang; Chen, Bo-Wei; Liu, Yuan-Yuan; Wang, Yin-Song; Zhang, Ning

    2016-01-01

    Sonodynamic therapy (SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment. PMID:27807500

  4. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    SciTech Connect

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-02-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  5. Providing massage therapy for people with advanced cancer: what to expect.

    PubMed

    Smith, Marlaine C; Yamashita, Traci E; Bryant, Lucinda L; Hemphill, Linnea; Kutner, Jean S

    2009-04-01

    There is very little information in the literature to prepare massage therapists for what they might expect when they provide treatment to people with advanced cancer in hospice or palliative care. We report an analysis of a subset of data collected from a large multi-site clinical trial of the efficacy of massage therapy for people with advanced cancer. This is the first analysis of empirical data of patient presentation, massage treatment environment, and the characteristics of massage provided for this population.

  6. Advances in targeting strategies for nanoparticles in cancer imaging and therapy

    NASA Astrophysics Data System (ADS)

    YheeThese Authors Contributed The Same., Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-10-01

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  7. Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes.

    PubMed

    Currey, Adam D; Bergom, Carmen; Kelly, Tracy R; Wilson, J Frank

    2015-01-01

    Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long-term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.

  8. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  9. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  10. Endoscopic therapy for early gastric cancer: Standard techniques and recent advances in ESD

    PubMed Central

    Kume, Keiichiro

    2014-01-01

    The technique of endoscopic submucosal dissection (ESD) is now a well-known endoscopic therapy for early gastric cancer. ESD was introduced to resect large specimens of early gastric cancer in a single piece. ESD can provide precision of histologic diagnosis and can also reduce the recurrence rate. However, the drawback of ESD is its technical difficulty, and, consequently, it is associated with a high rate of complications, the need for advanced endoscopic techniques, and a lengthy procedure time. Various advances in the devices and techniques used for ESD have contributed to overcoming these drawbacks. PMID:24914364

  11. HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

    PubMed Central

    Joy, Anil A.; Rayson, Daniel; McLeod, Deanna; Brezden-Masley, Christine; Boileau, Jean-François; Gelmon, Karen A.

    2013-01-01

    Untreated human epidermal growth factor receptor-2 (HER-2)-positive advanced breast cancer (ABC) is an aggressive disease, associated with a poor prognosis and short overall survival. HER-2-directed therapy prolongs both time to disease progression and overall survival when combined with chemotherapy and has become the standard of care for those with HER-2-positive breast cancer in the early and advanced settings. Despite the remarkable therapeutic impact HER-2-directed therapy has had on disease outcomes, some patients with HER-2-positive disease will have primary resistant disease and others will respond initially but will eventually have progression, underscoring the need for other novel therapeutic options. This article reviews recent phase III trial data and discusses a practical approach to sequencing of HER-2-directed therapy in patients with HER-2-positive ABC. The significant cumulative survival gains seen in these trials are slowly reshaping the landscape of HER-2-positive ABC outcomes. PMID:24212500

  12. Clinical advances in molecular biomarkers for cancer diagnosis and therapy.

    PubMed

    Sethi, Seema; Ali, Shadan; Philip, Philip A; Sarkar, Fazlul H

    2013-07-16

    Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer. Moreover, deregulating their activity offers novel cancer therapeutic approaches. The availability of high throughput techniques for the identification of altered cellular molecules allowed their use in cancer diagnosis. Their application to a variety of body specimens from blood to tissues has been helpful for appreciating their use in the clinical context. The development of innovative antibodies for immunohistochemical detection of proteins also assists in diagnosis and risk stratification. Overall, the novel cancer diagnostic tools have extended their application as prognostic risk factors and can be used as targets for personalized medicine.

  13. [Recurrence and survival rate of advanced gastric cancer after preoperative intraarterial EAP I injection therapy].

    PubMed

    Takeuchi, K; Taniguchi, H; Miyata, K; Koyama, H; Tanaka, H; Ueshima, Y; Okano, S; Oguro, A; Itoh, A; Sawai, K

    1993-08-01

    In our department, curative operations were performed for 32 patients with advanced gastric cancer from April 1989 to August 1990. Preoperative intra-arterial injection therapy with etoposide (100 mg), pirarubicin (20 mg) and cisplatin (20 mg) was given 18 patients. Recurrence and survival rate were investigated. The survival rate of patients with preoperative intra-arterial injection therapy 45 months after operation was 59.2%, while that of patients without preoperative intra-arterial injection therapy was 75.8%. There were no significant differences between these two groups. Three lymph node recurrences were seen in patients with preoperative intra-arterial injection therapy (recurrence rate, 16.7%). Four recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination 2, liver 1, local 1; recurrence rate, 28.6%). We earlier reported that preoperative intra-arterial cisplatin (40 or 60 mg) injection therapy may reduce the incidence of lymph node recurrence and liver metastasis but may not be effective to prevent postoperative peritoneal recurrence, while no peritoneal dissemination was observed in patients with preoperative intra-arterial EAP I injection therapy. Thus, it was concluded that further study of combination and dose of anti-cancer drug may improve effectiveness of preoperative intra-arterial injection therapy for gastric cancer.

  14. The steady progress of targeted therapies, promising advances for lung cancer

    PubMed Central

    Bombardelli, Lorenzo; Berns, Anton

    2016-01-01

    Lung cancer remains one of the most complex and challenging cancers, being responsible for almost a third of all cancer deaths. This grim picture seems however to be changing, for at least a subset of lung cancers. The number of patients who can benefit from targeted therapies is steadily increasing thanks to the progress made in identifying actionable driver lesions in lung tumours. The success of the latest generation of EGFR and ALK inhibitors in the clinic not only illustrates the value of targeted therapies, but also shows how almost inevitably drug resistance develops. Therefore, more sophisticated approaches are needed to achieve long-term remissions. Although there are still significant barriers to be overcome, technological advances in early detection of relevant mutations and the opportunity to test new drugs in predictive preclinical models justify the hope that we will overcome these obstacles. PMID:27350784

  15. Recent advances of thermally responsive nanogels for cancer therapy.

    PubMed

    Wang, Yajing; Xu, Hongjiang; Ma, Lin

    2015-01-01

    Thermally responsive nanogel drug delivery systems (TRNDDS) have been widely investigated as a new strategy for active targeting tumor therapy, as these can accumulate on the tumor site and/or release the payload at the desired site by structure changes rapidly once stimulated by temperature changes. In this review, we discuss the evolution of TRNDDS and future perspectives for antitumor drug and gene delivery. With further understanding of the specificity of tumor site at the cellular and molecular level, in parallel with the development of nanomaterial design and preparation, TRNDDS show great potential for tumor targeting therapy. PMID:26478174

  16. Recent Advances in Upconversion Nanoparticles-Based Multifunctional Nanocomposites for Combined Cancer Therapy.

    PubMed

    Tian, Gan; Zhang, Xiao; Gu, Zhanjun; Zhao, Yuliang

    2015-12-16

    Lanthanide-doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous-wave near-infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue-penetration ability and high signal-to-noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging-guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co-delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti-cancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs-based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs-based composites. The future prospects and challenges in this emerging field will be also discussed.

  17. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  18. Plant coumestans: recent advances and future perspectives in cancer therapy.

    PubMed

    Nehybová, Tereza; Šmarda, Jan; Beneš, Petr

    2014-01-01

    Natural products are often used in drug development due to their ability to form unique and diverse chemical structures. Coumestans are polycyclic aromatic plant secondary metabolites containing a coumestan moiety, which consists of a benzoxole fused to a chromen-2-one to form 1-Benzoxolo[3,2-c]chromen-6-one. These natural compounds are known for large number of biological activities. Many of their biological effects can be attributed to their action as phytoestrogens and polyphenols. In the last decade, anticancer effects of these compounds have been described in vitro but there is only limited number of studies based on models in vivo. More information concerning their in vivo bioavailability, stability, metabolism, toxicity, estrogenicity, cellular targets and drug interactions is therefore needed to proceed further to clinical studies. This review focuses on coumestans exhibiting anticancer properties and summarizes mechanisms of their toxicity to cancer cells. Moreover, the possible role of coumestans in cancer prevention is discussed.

  19. Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

    SciTech Connect

    Roof, Kevin S. . E-mail: kroof@sero.net; Coen, John; Lynch, Thomas J.; Wright, Cameron; Fidias, Panos; Willett, Christopher G.; Choi, Noah C.

    2006-07-15

    Purpose: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted.

  20. Selective androgen receptor modulators as improved androgen therapy for advanced breast cancer.

    PubMed

    Coss, Christopher C; Jones, Amanda; Dalton, James T

    2014-11-01

    Androgens were at one time a therapeutic mainstay in the treatment of advanced breast cancer. Despite comparable efficacy, SERMs and aromatase inhibitors eventually became the therapies of choice due to in part to preferred side-effect profiles. Molecular characterization of breast tumors has revealed an abundance of androgen receptor expression but the choice of an appropriate androgen receptor ligand (agonist or antagonist) has been confounded by multiple conflicting reports concerning the role of the receptor in the disease. Modern clinical efforts have almost exclusively utilized antagonists. However, the recent clinical development of selective androgen receptor modulators with greatly improved side-effect profiles has renewed interest in androgen agonist therapy for advanced breast cancer.

  1. New molecular targeted therapies for advanced non-small-cell lung cancer

    PubMed Central

    Méndez, Míriam; Custodio, Ana; Provencio, Mariano

    2011-01-01

    Non-small-cell lung cancer (NSCLC) is a uniformly fatal disease and most patients will present with advanced stage. Treatment outcomes remain unsatisfactory, with low long-term survival rates. Standard treatment, such as palliative chemotherapy and radiotherapy, offers a median survival not exceeding 1 year. Hence, considerable efforts have started to be made in order to identify new biological agents which may safely and effectively be administered to advanced NSCLC patients. Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. However, novel targeted therapies that interfere with other dysregulated pathways in lung cancer are already in the clinic. This review outlines the most promising research approaches to the treatment of NSCLC, discussed according to the specific molecular pathway targeted. PMID:22263060

  2. Advanced gastric cancer (GC) and cancer of the gastro-oesophageal junction (GEJ): focus on targeted therapies.

    PubMed

    Cappetta, Alessandro; Lonardi, Sara; Pastorelli, Davide; Bergamo, Francesca; Lombardi, Giuseppe; Zagonel, Vittorina

    2012-01-01

    Despite recent improvements in surgical techniques and chemotherapy treatments, locally advanced/metastatic gastroesophageal junction (GEJ) and gastric cancer (GC) are still associated with poor clinical outcome. However, increased understanding of molecular mechanisms underlying carcinogenesis and its implementation in the treatment of breast, colon, lung, and other cancers in recent years have spurred focus on the development and incorporation of targeted agents in current therapeutic options for this difficult-to-treat disease. Such agents have the ability to target a variety of cancer relevant targets, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) and its receptor. In this review, we describe the current status of targeted therapies in the treatment of advanced GC and GEJ cancer, focusing on pre-clinical and clinical data available on monoclonal antibodies and tyrosine kinase inhibitors acting in these pathways, including completed and ongoing phase III studies.

  3. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  4. Management of advanced bladder cancer in the era of targeted therapies.

    PubMed

    Soave, A; Engel, O; Von Amsberg, G; Becker, A; Dahlem, R; Shariat, S F; Fisch, M; Rink, M

    2015-06-01

    Systemic chemotherapy is the standard treatment of advanced and metastatic urothelial carcinoma of the bladder (UCB). Unfortunately, systemic chemotherapy is ineffective in a significant number of patients, while side effects occur frequently. Detailed molecular-genetic investigations revealed a broad heterogeneity of underlying genomic mutations in UCB and led to the detection of cancer-specific therapeutic targets. These findings may allow a more tailored and individualized patient-based therapy, focusing on specific genomic variations, which may cause chemo-resistance in patients progressing or relapsing after standard chemotherapy. Targeted therapies hold the potential to be more effective in inhibiting cancer cell growth and progression, as well as to cause fewer side effects. While targeted therapies have been successfully established in the treatment of various malignancies including renal cell carcinoma, the clinical impact of these modern treatment strategies still remains unsettled for UCB. In this review, we comprehensively summarize the most current and relevant findings on targeted therapy in advanced and metastatic UCB, elucidating chances and limitations and discussing future perspectives.

  5. Dawn of advanced molecular medicine: nanotechnological advancements in cancer imaging and therapy.

    PubMed

    Kaittanis, Charalambos; Shaffer, Travis M; Thorek, Daniel L J; Grimm, Jan

    2014-01-01

    Nanotechnology plays an increasingly important role not only in our everyday life (with all its benefits and dangers) but also in medicine. Nanoparticles are to date the most intriguing option to deliver high concentrations of agents specifically and directly to cancer cells; therefore, a wide variety of these nanomaterials has been developed and explored. These span the range from simple nanoagents to sophisticated smart devices for drug delivery or imaging. Nanomaterials usually provide a large surface area, allowing for decoration with a large amount of moieties on the surface for either additional functionalities or targeting. Besides using particles solely for imaging purposes, they can also carry as a payload a therapeutic agent. If both are combined within the same particle, a theranostic agent is created. The sophistication of highly developed nanotechnology targeting approaches provides a promising means for many clinical implementations and can provide improved applications for otherwise suboptimal formulations. In this review we will explore nanotechnology both for imaging and therapy to provide a general overview of the field and its impact on cancer imaging and therapy. PMID:25271430

  6. Dawn of Advanced Molecular Medicine: Nanotechnological Advancements in Cancer Imaging and Therapy

    PubMed Central

    Kaittanis, Charalambos; Shaffer, Travis M.; Thorek, Daniel L. J.; Grimm, Jan

    2014-01-01

    Nanotechnology plays an increasingly important role not only in our everyday life (with all its benefits and dangers) but also in medicine. Nanoparticles are to date the most intriguing option to deliver high concentrations of agents specifically and directly to cancer cells; therefore, a wide variety of these nanomaterials has been developed and explored. These span the range from simple nanoagents to sophisticated smart devices for drug delivery or imaging. Nanomaterials usually provide a large surface area, allowing for decoration with a large amount of moieties on the surface for either additional functionalities or targeting. Besides using particles solely for imaging purposes, they can also carry as a payload a therapeutic agent. If both are combined within the same particle, a theranostic agent is created. The sophistication of highly developed nanotechnology targeting approaches provides a promising means for many clinical implementations and can provide improved applications for otherwise suboptimal formulations. In this review we will explore nanotechnology both for imaging and therapy to provide a general overview of the field and its impact on cancer imaging and therapy. PMID:25271430

  7. Beyond HER2: recent advances and future directions in targeted therapies in esophagogastric cancers

    PubMed Central

    2016-01-01

    Esophagogastric cancers (EGCa) are a leading cause of cancer related mortality worldwide. It has been recognized that they represent heterogenous diseases based on histology and anatomy. However, it is also increasingly evident that these are diverse malignancies based on genetic alterations, and this is increasingly making these diseases amenable to targeted therapies. While epidermal growth factor receptor (EGFR) and mTOR inhibitors have failed to prove effective in the treatment of advanced EGCa, vascular endothelial growth factor (VEGF) inihibitor have now been demonstrated to improve survival, at least in the 2nd line setting of adenocarcinomas. Other promising approaches are being investigated, including targeted therapies such as MET and FGFR inhibitors, as well as immunotherapy and agents that may affect synthetic lethality. PMID:27747090

  8. Exceptional Response to Systemic Therapy in Advanced Metastatic Gastric Cancer: A Case Report

    PubMed Central

    Hartley, Marion; Manning, Maria A; Carroll, John E; Xiu, Joanne; Smaglo, Brandon G; Mikhail, Sameh; Salem, Mohamed E

    2016-01-01

    Gastroesophageal adenocarcinomas represent one of the top five most common types of cancer worldwide. Despite significant advancement, it is still not known which first-line chemotherapy option is best matched to an individual patient. The vast advances in molecular biology have led to the discovery of many potential predictive biomarkers, such as HER-2 neu, thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and topoisomerase-1 (TOPO1). These markers could allow us to select treatment based on an individual’s tumor profile, resulting in an improvement of outcome. Our report highlights two patients with metastatic gastric cancer that achieved an exceptional response with traditional therapy and provides insights into the future perspectives of molecular profile-directed chemotherapy. PMID:26918225

  9. Developing treatment and control conditions in a clinical trial of massage therapy for advanced cancer.

    PubMed

    Smith, Marlaine; Kutner, Jean; Hemphill, Linnea; Yamashita, Traci; Felton, Susanne

    2007-01-01

    The purpose of this article is to describe the challenges faced by a research team in developing treatment and control conditions in a study of the efficacy of massage therapy for advanced cancer. Five design considerations were addressed related to developing a massage therapy protocol: (1) dosage, that is, the number, spacing and length of treatments; (2) type of massage therapy; (3) degree to which the protocol for the treatment is standardized; (4) qualifications of the persons providing the treatment; and (5) conditions under which the treatment is provided. Five criteria for structuring the control condition of the study are elaborated: (1) equivalency of contact; (2) similarity of form; (3) minimum adverse or negative effects; (4) expectancy of therapeutic benefit; and (5) minimum therapeutic benefit.

  10. Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

    PubMed

    Nissenbaum, M; Browde, S; Bezwoda, W R; de Moor, N G; Derman, D P

    1984-01-01

    Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

  11. Targeted therapy for advanced gastric cancer: A review of current status and future prospects

    PubMed Central

    Kanat, Ozkan; O’Neil, Bert; Shahda, Safi

    2015-01-01

    In the West in particular, the vast majority of gastric cancer (GC) patients present with advanced-stage disease. Although combination chemotherapy is still the most important component of treatment for these patients, it confers a modest survival advantage. Recently, increased knowledge of the key molecular signaling pathways involved in gastric carcinogenesis has led to the discovery of specific molecular-targeted therapeutic agents. Some of these agents such as trastuzumab and ramucirumab have changed the treatment paradigm for this disease. In this paper, we will summarize the current clinical status of targeted drug therapy in the management of GC. PMID:26690491

  12. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    PubMed

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    mainly deliver chemotherapeutic agents to molecular targets overexpressed on the surface of tumor cells. In particular, we offer a detailed description of different cytotoxic drug carriers, such as liposomes, carbon nanotubes, dendrimers, polymeric micelles, polymeric conjugates and polymeric nanoparticles, in passive and active targeted cancer therapy, by enhancing the permeability and retention or by the functionalization of the surface of the carriers, respectively, emphasizing those that have received FDA approval or are part of the most important clinical studies up to date. These drug carriers not only transport the chemotherapeutic agents to tumors, avoiding normal tissues and reducing toxicity in the rest of the body, but also protect cytotoxic drugs from degradation, increase the half-life, payload and solubility of cytotoxic agents and reduce renal clearance. Despite the many advantages of all the anticancer drug carriers analyzed, only a few of them have reached the FDA approval, in particular, two polymer-protein conjugates, five liposomal formulations and one polymeric nanoparticle are available in the market, in contrast to the sixteen FDA approval of monoclonal antibodies. However, there are numerous clinical trials in progress of polymer-protein and polymer-drug conjugates, liposomal formulations, including immunoliposomes, polymeric micelles and polymeric nanoparticles. Regarding carbon nanotubes or dendrimers, there are no FDA approvals or clinical trials in process up to date due to their unresolved toxicity. Moreover, we analyze in detail the more promising and advanced preclinical studies of the particular case of polymeric nanoparticles as carriers of different cytotoxic agents to active and passive tumor targeting published in the last 5 years, since they have a huge potential in cancer therapy, being one of the most widely studied nano-platforms in this field in the last years. The interest that these formulations have recently achieved is

  13. Advances in targeted and immunobased therapies for colorectal cancer in the genomic era

    PubMed Central

    Seow, Heng Fong; Yip, Wai Kien; Fifis, Theodora

    2016-01-01

    Targeted therapies require information on specific defective signaling pathways or mutations. Advances in genomic technologies and cell biology have led to identification of new therapeutic targets associated with signal-transduction pathways. Survival times of patients with colorectal cancer (CRC) can be extended with combinations of conventional cytotoxic agents and targeted therapies. Targeting EGFR- and VEGFR-signaling systems has been the major focus for treatment of metastatic CRC. However, there are still limitations in their clinical application, and new and better drug combinations are needed. This review provides information on EGFR and VEGF inhibitors, new therapeutic agents in the pipeline targeting EGFR and VEGFR pathways, and those targeting other signal-transduction pathways, such as MET, IGF1R, MEK, PI3K, Wnt, Notch, Hedgehog, and death-receptor signaling pathways for treatment of metastatic CRC. Additionally, multitargeted approaches in combination therapies targeting negative-feedback loops, compensatory networks, and cross talk between pathways are highlighted. Then, immunobased strategies to enhance antitumor immunity using specific monoclonal antibodies, such as the immune-checkpoint inhibitors anti-CTLA4 and anti-PD1, as well as the challenges that need to be overcome for increased efficacy of targeted therapies, including drug resistance, predictive markers of response, tumor subtypes, and cancer stem cells, are covered. The review concludes with a brief insight into the applications of next-generation sequencing, expression profiling for tumor subtyping, and the exciting progress made in in silico predictive analysis in the development of a prescription strategy for cancer therapy. PMID:27099521

  14. Systemic therapy in the management of metastatic or advanced salivary gland cancers

    PubMed Central

    2012-01-01

    Salivary gland cancers are very rare tumors. They are characterized by a histologic heterogeneity and a poor outcome. According to this rarity, few prospective data are available to date. No standard recommendations could be held for the use of systemic therapy in these tumors. Several case reports and small studies have investigated the contribution of different agents of chemotherapy. With the extension of molecular biology approach in oncology several signaling pathways have been discovered in different cancers including salivary gland cancers; thus a number of targeted therapies have been investigated. This paper reviewed exhaustively the studies investigating the role of systemic therapies (chemotherapy, targeted therapy, hormone therapy) in salivary gland cancers. PMID:22558945

  15. The use of music therapy to address the suffering in advanced cancer pain.

    PubMed

    Magill, L

    2001-01-01

    Pain associated with advanced cancer is multifaceted and complex, and is influenced by physiological, psychological, social, and spiritual phenomena. Suffering may be identified in patients when pain is associated with impending loss, increased dependency, and an altered understanding of one's existential purpose. Comprehensive pain management aims to address problematic symptoms in order to improve comfort, peace of mind, and quality of life. Music therapy is a treatment modality of great diversity that can offer a range of benefits to patients with advanced cancer pain and symptoms of suffering. Music therapists perform comprehensive assessments that include reviews of social, cultural, and medical history; current medical status; and the ways in which emotions are affecting the pain. A variety of music therapy techniques may be used, including vocal techniques, listening, and instrumental techniques. These techniques provide opportunities for exploration of the feelings and issues compounding the pain experience. Case examples are presented to demonstrate the "lifting", "transporting", and "bringing of peace" qualities of music that offer patients moments of release, reflection, and renewal. PMID:11816757

  16. Nutritional rehabilitation in patients with advanced head and neck cancer receiving radiation therapy.

    PubMed

    Daly, J M; Hearne, B; Dunaj, J; LePorte, B; Vikram, B; Strong, E; Green, M; Muggio, F; Groshen, S; DeCosse, J J

    1984-10-01

    maintained mean mid-arm circumference and recovered mean serum albumin levels after radiation therapy in contrast with the orally fed group. Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy, however, was unchanged.

  17. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  18. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  19. KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer

    PubMed Central

    2010-01-01

    specimens. It is believed that KRAS status is not affected by treatments, therefore, for patients for whom surgical tissue is available for KRAS testing, additional biopsies prior to treatment with these targeted agents is not necessary. For patients that have not undergone surgery or for whom surgical tissue is not available, a biopsy of either the primary or metastatic site is required to determine their KRAS status. This is possible as status at the metastatic and primary tumour sites is considered to be similar. Research Question To determine if there is predictive value of KRAS testing in guiding treatment decisions with anti-EGFR targeted therapies in advanced colorectal cancer patients refractory to chemotherapy. Research Methods Literature Search The Medical Advisory Secretariat followed its standard procedures and on May 18, 2010, searched the following electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment database. The subject headings and keywords searched included colorectal cancer, cetuximab, panitumumab, and KRAS testing. The search was further restricted to English-language articles published between January 1, 2009 and May 18, 2010 resulting in 1335 articles for review. Excluded were case reports, comments, editorials, nonsystematic reviews, and letters. Studies published from January 1, 2005 to December 31, 2008 were identified in a health technology assessment conducted by the Agency for Healthcare Research and Quality (AHRQ), published in 2010. In total, 14 observational studies were identified for inclusion in this EBA: 4 for cetuximab monotherapy, 7 for the cetuximab-irinotecan combination therapy, and 3 to be included in the review for panitumumab monotherapy Inclusion Criteria English-language articles, and English or French-language HTAs

  20. Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.

    PubMed

    Nakao, Toshihiro; Iwata, Takashi; Hotchi, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Nishi, Masaaki; Takasu, Chie; Eto, Shohei; Teraoku, Hiroki; Shimada, Mitsuo

    2015-10-01

    Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non‑responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.

  1. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis.

    PubMed

    Kimura, Masakazu; Miyajima, Kuniharu; Kojika, Masakazu; Kono, Takafumi; Kato, Harubumi

    2015-10-23

    Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT) combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi) bronchial stenosis and obstruction. We present data for 12 (eight men, four women) consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58-80 years), and the stages of cancer were IIA-IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%-100%), 15% (range, 15%-99%), and 15% (range 15%-60%), respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction.

  2. Preoperative Kidney Tumor Embolization as Procedure for Therapy of Advanced Kidney Cancer

    PubMed Central

    Jaganjac, Suad; Schefe, L.; Avdagić, Edin; Spahović, Hajrudin; Hiros, Mustafa

    2014-01-01

    ABSTRACT Introduction: Preoperative kidney tumor embolization is standard procedure for therapy in advanced kidney cancer. Preoperative embolization has a goal to reduce intraoperative bleeding and also to shorten the time of surgery. Materials and methods: We retrospectively observed 50 patients between 2000-2011, in which the preoperative embolization was performed. Mean age of patients was 64 years. All patients with preoperative embolization were compared with the group of 51 patients from Urology Sarajevo, who underwent nephrectomy without preoperative embolization. Results: Symptoms that are dominating among patients were haematuria and pain. Analysis of mean size of tumors based on CT evaluation showed statistically significance in between the biggest size of tumors in group from Hamburg (9.11±3cm) and the smallest size of tumors in Sarajevo group (4.94±1.6cm) p=0.0001. Reason for this is difference in selection of patients for treatment in Hamburg from Sarajevo. Conclusion Kidney as functional finishing organ is extremely suitable for transcatheter therapeutic procedures. The gold standard in the treatment of advanced and metastatic tumor is the nephrectomy. As preparation for nephrectomy in metastatic cancer total capillary embolization is performed. After embolization, surgery is shorter, procedure can be done 24-48 hours after embolization or delayed nephrectomy done 2-3 weeks after the intervention. PMID:25568577

  3. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    PubMed Central

    Li, Kaichun; Li, Jin

    2016-01-01

    Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

  4. [Research advances of K-ras mutation in the prognosis and targeted therapy of gastric cancer].

    PubMed

    Huang, Y; Wei, J; Liu, B R

    2016-02-01

    K-ras mutations have been described in 30% of human cancers with significantly different mutation frequencies. High K-ras mutation frequency is found in many cancers such as pancreas and lung cancers, whereas, gastric cancer has a relatively low K-ras mutation frequency. In recent years, numerous researches have focused on the K-ras mutation in gastric cancer. This review summarizes the K-ras mutation frequency in gastric cancer, the relationship of K-ras mutation with clinicopathologic features and prognosis of gastric cancer patients, targeted therapy for K-ras mutated gastric cancer, some small-molecular inhibitors of K-ras, and development of targeted therapy drugs for K-ras signaling pathway in gastric cancer.

  5. Cancer Therapy

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The patient shown is undergoing cancer radiation treatment in a hospital-like atmosphere but he is not in a hospital. The treatment room is at NASA's Lewis Research Center, Cleveland, Ohio. It is a converted portion of the Center's cyclotron facility, originally designed for radiation studies related to nuclear propulsion for aircraft and spacecraft. Under an agreement between the Center and the Cleveland Clinic Foundation, the 50 million volt cyclotron is now being used to evaluate the effectiveness of "fast neutron" therapy in the treatment of cancerous tumors.

  6. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    SciTech Connect

    Appelt, Ane L.; Ploen, John; Vogelius, Ivan R.; Bentzen, Soren M.; Jakobsen, Anders

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

  7. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    PubMed

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  8. National Cancer Data Base Analysis of Radiation Therapy Consolidation Modality for Cervical Cancer: The Impact of New Technological Advancements

    SciTech Connect

    Gill, Beant S.; Lin, Jeff F.; Krivak, Thomas C.; Sukumvanich, Paniti; Laskey, Robin A.; Ross, Malcolm S.; Lesnock, Jamie L.; Beriwal, Sushil

    2014-12-01

    Purpose: To utilize the National Cancer Data Base to evaluate trends in brachytherapy and alternative radiation therapy utilization in the treatment of cervical cancer, to identify associations with outcomes between the various radiation therapy modalities. Methods and Materials: Patients with International Federation of Gynecology and Obstetrics stage IIB-IVA cervical cancer in the National Cancer Data Base who received treatment from January 2004 to December 2011 were analyzed. Overall survival was estimated by the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify factors associated with type of boost radiation modality used and its impact on survival. Results: A total of 7654 patients had information regarding boost modality. A predominant proportion of patients were Caucasian (76.2%), had stage IIIB (48.9%) disease with squamous (82.0%) histology, were treated at academic/research centers (47.7%) in the South (34.8%), and lived 0 to 5 miles (27.9%) from the treating facility. A majority received brachytherapy (90.3%). From 2004 to 2011, brachytherapy use decreased from 96.7% to 86.1%, whereas intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) use increased from 3.3% to 13.9% in the same period (P<.01). Factors associated with decreased brachytherapy utilization included older age, stage IVA disease, smaller tumor size, later year of diagnosis, lower-volume treatment centers, and facility type. After controlling for significant factors from survival analyses, IMRT or SBRT boost resulted in inferior overall survival (hazard ratio, 1.86; 95% confidence interval, 1.35-2.55; P<.01) as compared with brachytherapy. In fact, the survival detriment associated with IMRT or SBRT boost was stronger than that associated with excluding chemotherapy (hazard ratio, 1.61′ 95% confidence interval, 1.27-2.04′ P<.01). Conclusions: Consolidation brachytherapy is a critical treatment component for

  9. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    SciTech Connect

    Thorek, Daniel L.J.; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James

    2015-10-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

  10. Palliative Therapy for Gallbladder Cancer

    MedlinePlus

    ... based on the extent of gallbladder cancer Palliative therapy for gallbladder cancer Palliative therapy is treatment given to help control or reduce ... to advance quickly, doctors try to use palliative therapies that are less likely to affect a person’s ...

  11. Advanced Pancreatic Cancer: Flourishing Novel Approaches in the Era of Biological Therapy

    PubMed Central

    Chiu, Joanne W.; Wong, Hilda; Leung, Roland; Pang, Roberta; Cheung, Tan-To; Fan, Sheung-Tat; Poon, Ronnie

    2014-01-01

    The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance. PMID:25117068

  12. Advanced pancreatic cancer: flourishing novel approaches in the era of biological therapy.

    PubMed

    Chiu, Joanne W; Wong, Hilda; Leung, Roland; Pang, Roberta; Cheung, Tan-To; Fan, Sheung-Tat; Poon, Ronnie; Yau, Thomas

    2014-09-01

    The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance. PMID:25117068

  13. Targeted therapy for advanced hepatocellular cancer in the elderly: focus on sorafenib.

    PubMed

    Germano, D; Tinessa, V; Barletta, E; Cannella, L; Daniele, B

    2013-11-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Worldwide progressive population aging demands consensus development for decision making when treating elderly patients. Age itself might not be a critical determinant for the selection of a therapeutic option. In the past few years, the mechanisms of hepato-carcinogenesis have been elucidated, and the involvement of a number of pathways, including angiogenesis, aberrant signal transduction, and dysregulated cell cycle control, have been demonstrated, leading to evaluation of the activity and toxicity of some of the new molecularly targeted agents. Sorafenib was demonstrated to significantly increase the survival of patients with advanced HCC in two prospective, randomized, placebo-controlled trials. Subsequently, a number of retrospective or prospective studies have indicated that the effectiveness of sorafenib therapy in the treatment of HCC is similar in elderly and non-elderly patients. The aim of this review is to describe the impact of age on the effects of sorafenib-targeted therapy in patients with HCC, and the next treatment options with new targeted agents (everolimus, tivantinib, linifanib, etc.). PMID:24097332

  14. Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.

    PubMed

    Friedman, Kenneth; Resnick, Murray B; Safran, Howard

    2015-10-01

    The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic alterations in genes commonly mutated in cancer. However, several unexpected genomic alterations were discovered in certain cancers with potential therapeutic intervention. Most cancers contained "actionable" genomic alterations despite being of advanced stage. Our experience demonstrates that application of NGS in the clinical setting contributes both to increasing the therapeutic armamentarium as well as our understanding of tumor biology.

  15. Predictors for resectability and survival in locally advanced pancreatic cancer after gemcitabine-based neoadjuvant therapy

    PubMed Central

    2014-01-01

    Background To evaluate the predictors for resectability and survival of patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based neoadjuvant therapy (GBNAT). Methods Between May 2003 and Dec 2009, 41 tissue-proved LAPC were treated with GBNAT. The location of pancreatic cancer in the head, body and tail was 17, 18 and 6 patients respectively. The treatment response was evaluated by RECIST criteria. Surgical exploration was based on the response and the clear plan between tumor and celiac artery/superior mesentery artery. Kaplan–Meier analysis and Cox Model were used to calculate the resectability and survival rates. Results Finally, 25 patients received chemotherapy (CT) and 16 patients received concurrent chemoradiation therapy (CRT). The response rate was 51% (21 patients), 2 CR (1 in CT and 1 in CRT) and 19 PR (10 in CT and 9 in CRT). 20 patients (48.8%) were assessed as surgically resectable, in which 17 (41.5%) underwent successful resection with a 17.6% positive-margin rate and 3 failed explorations were pancreatic head cancer for dense adhesion. Two pancreatic neck cancer turned fibrosis only. Patients with surgical intervention had significant actuarial overall survival. Tumor location and post-GBNAT CA199 < 152 were predictors for resectability. Post-GBNAT CA-199 < 152 and post-GBNAT CA-125 < 32.8 were predictors for longer disease progression-free survival. Pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, and post-op CEA < 6 were predictors for longer overall survival. Conclusion Tumor location and post-GBNAT CA199 < 152 are predictors for resectability while pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, post-GBNAT CA-199 < 152 and post-op CEA < 6 are survival predictors in LAPC patients with GBNAT. PMID:25258022

  16. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

    PubMed Central

    Chen, Yingtai; Che, Xu; Zhang, Jianwei; Huang, Huang; Zhao, Dongbing; Tian, Yantao; Li, Yexiong; Feng, Qinfu; Zhang, Zhihui; Jiang, Qinglong; Zhang, Shuisheng; Tang, Xiaolong; Huang, Xianghui; Chu, Yunmian; Zhang, Jianghu; Sun, Yuemin; Zhang, Yawei; Wang, Chengfeng

    2016-01-01

    Abstract To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT. A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47–0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32–0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04–0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment. Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID:27661028

  17. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    SciTech Connect

    Martinez, Steve R.; Beal, Shannon H.; Chen, Steven L.; Canter, Robert J.; Khatri, Vijay P.; Chen, Allen; Bold, Richard J.

    2010-11-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  18. Advances in targeted therapies and new promising targets in esophageal cancer

    PubMed Central

    Belkhiri, Abbes; El-Rifai, Wael

    2015-01-01

    Esophageal cancer, comprising squamous carcinoma and adenocarcinoma, is a leading cause of cancer-related death in the world. Notably, the incidence of esophageal adenocarcinoma has increased at an alarming rate in the Western world. Unfortunately, the standard first-line chemo-radiotherapeutic approaches are toxic and of limited efficacy in the treatment of a significant number of cancer patients. The molecular analysis of cancer cells has uncovered key genetic and epigenetic alterations underlying the development and progression of tumors. These discoveries have paved the way for the emergence of targeted therapy approaches. This review will highlight recent progress in the development of targeted therapies in esophageal cancer. This will include a review of drugs targeting receptor tyrosine kinases and other kinases in esophageal cancer. Additional studies will be required to develop a rational integration of these targeted agents with respect to histologic types of esophageal cancer and the optimal selection of cancer patients who would most likely benefit from targeted therapy. Identification of AURKA and AXL as key molecular players in esophageal tumorigenesis and drug resistance strongly justifies the evaluation of the available drugs against these targets in clinical trials. PMID:25593196

  19. Esophagus Cancer: Palliative Therapy

    MedlinePlus

    ... your doctor about cancer of the esophagus? Palliative therapy for cancer of the esophagus Palliative therapy is ... therapy Electrocoagulation Laser ablation Argon plasma coagulation Radiation therapy External-beam radiation can often help relieve some ...

  20. Reverse-contrast imaging and targeted radiation therapy of advanced pancreatic cancer models

    PubMed Central

    Thorek, Daniel L.J.; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, H. David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James

    2015-01-01

    Purpose To evaluate the feasibility of delivering experimental radiotherapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by X-ray CT. With this technique we delineated the pancreas, and both orthotopic xenografts and genetically engineered disease. CT imaging was validated by comparison with magnetic resonance (MR) imaging. Therapeutic radiation was delivered via a 1 cm diameter field. Selective X-ray radiation therapy (XRT) of the non-invasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360-degree arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic XRT to orthotopic tumors. Results Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times post-treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions This advance permits evaluation of radiation planning and dosing parameters. Accurate non-invasive longitudinal imaging and monitoring of tumor progression and therapeutic response in pre-clinical models is now possible, and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response. PMID:26238952

  1. Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer

    SciTech Connect

    Estorch, M.; Carrio, I.; Berna, L.; Martinez-Duncker, C.; Alonso, C.; Germa, J.R.; Ojeda, B. )

    1990-12-01

    Indium-111-antimyosin ({sup 111}In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2). Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25. Left ventricular ejection fraction (EF) was determined before and after chemotherapy. Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01)). HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05). Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients. Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy.

  2. Side effects of bone-targeted therapies in advanced breast cancer.

    PubMed

    Domschke, Christoph; Schuetz, Florian

    2014-10-01

    In up to 75% of cases, advanced breast cancer patients eventually develop bone metastases with often debilitating skeletal-related events (SREs). Osteoclast inhibitors are commonly used as therapeutic mainstay with clinical studies showing superiority of denosumab over bisphosphonates (e.g., zoledronate) for the prevention of SREs. The present review discusses the adverse event profile of these agents, and addresses the prevention and management of untoward side effects. Adverse events associated with osteoclast inhibitors comprise osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with denosumab, particularly in severe renal dysfunction. During therapy, the appropriate prevention of these adverse events includes close attention to dental health, avoidance of invasive dental procedures, supplementation with calcium and vitamin D unless patients are hypercalcemic, and regular monitoring of relevant serum values. Relating to the risk of nephrotoxicity, bisphosphonates but not denosumab have been incriminated. Therefore, serum creatinine levels should be checked prior to each dose of zoledronate, and in severe renal dysfunction (creatinine clearance < 30 ml/min) zoledronate is contraindicated anyway. Acute-phase reactions are particularly linked to bisphosphonates. Consequently, if these adverse events predominate, switching to denosumab is recommended. PMID:25759613

  3. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    NASA Astrophysics Data System (ADS)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  4. Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

  5. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    SciTech Connect

    Valentini, Anna Lia; Gui, Benedetta; D'Agostino, Giuseppe Roberto; Mattiucci, Giancarlo; Clementi, Valeria; Di Molfetta, Ippolita Valentina; Bonomo, Pierluigi; Mantini, Giovanna

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  6. Therapeutic targeting of the phosphatidylinositol 3-kinase signaling pathway: novel targeted therapies and advances in the treatment of colorectal cancer

    PubMed Central

    Yu, Ming

    2012-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the USA, and more effective treatment of CRC is therefore needed. Advances in our understanding of the molecular pathogenesis of this malignancy have led to the development of novel molecule-targeted therapies. Among the most recent classes of targeted therapies being developed are inhibitors targeting the phosphatidylinositol 3-kinase (PI3K) signaling pathway. As one of the most frequently deregulated pathways in several human cancers, including CRC, aberrant PI3K signaling plays an important role in the growth, survival, motility and metabolism of cancer cells. Targeting this pathway therefore has considerable potential to lead to novel and more effective treatments for CRC. Preclinical and early clinical studies have revealed the potential efficacy of drugs that target PI3K signaling for the treatment of CRC. However, a major challenge that remains is to study these agents in phase III clinical trials to see whether these early successes translate into better patient outcomes. In this review we focus on providing an up-to-date assessment of our current understanding of PI3K signaling biology and its deregulation in the molecular pathogenesis of CRC. Advances in available agents and challenges in targeting the PI3K signaling pathway in CRC treatment will be discussed and placed in the context of the currently available therapies for CRC. PMID:22973417

  7. [Advanced radiation therapy project for cancer treatment--from Hokkaido to the world, the world access to Hokkaido].

    PubMed

    Shimizu, Shinichi; Tsuchiya, Kazuhiko; Takao, Seishin; Shirato, Hiroki

    2014-05-01

    Cancer is the most major cause of death in Japan recently. In this symposium, we explained advanced treatment technology for cancer treatment, now used and that will be used in near future at the Hokkaido University Hospital. Intensity Moderated Radiation Therapy (IMRT) and Proton Beam Therapy (PBT) are considered to be the most promising and advanced technologies for cancer treatment. Various kinds of radiation treatment equipment and methods have been developed and constructed at the Hokkaido University. One of the most worlds wide famous one is the real time tumor tracking radiotherapy system. The FIRST (Funding for World-Leading Innovative R&D on Science and Technology) Program has been supporting us to produce cutting-edge technology. We hope that this symposium would help the audience to understand the latest technology for cancer treatment especially in the field of radiation therapy and also we wish the audience would recognize the importance of the research aspect that have been performed at Hokkaido University and its Hospital.

  8. [Recurrence and survival rate of advanced gastric cancer after preoperative EAP-II intra-arterial infusion therapy].

    PubMed

    Masuyama, M; Taniguchi, H; Takeuchi, K; Miyata, K; Koyama, H; Tanaka, H; Higashida, T; Koishi, Y; Mugitani, T; Yamaguchi, T

    1994-09-01

    Ninety-eight patients with advanced gastric cancers underwent gastrectomy from Jan. 1989 to Dec. 1991. For these patients, preoperative intra-arterial injection therapy using EAP-II (etoposide 100 mg, epirubicin 20 mg, carboplatin 100 mg) was given to 24 patients. In this report, the recurrence and survival rate of these patients were investigated. After curative resection, the survival rate of patients with EAP-II 36 months after operation was 76.9%, while that of patients without EAP-II was 78.6%. There were no significant differences between these two groups. Two peritoneal carcinomatoses and two liver metastases were seen in patients with EAP-II (recurrence rate, 30.7%). Eight recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination, 4; local recurrence, 3; lymph node recurrence, 1). Previously, we reported that drugs were remarkably accumulated in gastric cancer tissue and regional lymph nodes after EAP-II intra-arterial injection therapy. This high accumulation might cause no local or lymph node recurrence was seen in patient with EAP-II. Thus, it was concluded that preoperative EAP-II intra-arterial injection may prevent local and lymph node recurrences, and that further study of the combination and dose of anti-cancer drug needed to improve the postoperative survival rate in advanced gastric cancer patients.

  9. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  10. Translational research on advanced therapies.

    PubMed

    Belardelli, Filippo; Rizza, Paola; Moretti, Franca; Carella, Cintia; Galli, Maria Cristina; Migliaccio, Giovanni

    2011-01-01

    Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP) are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP) facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues) is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

  11. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

    PubMed

    Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

    2011-06-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.

  12. Heavy Charged Particle Radiobiology: Using Enhanced Biological Effectiveness and Improved Beam Focusing to Advance Cancer Therapy

    PubMed Central

    Allen, Christopher; Borak, Thomas B.; Tsujii, Hirohiko; Nickoloff, Jac A.

    2011-01-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. PMID:21376738

  13. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

    PubMed

    Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

    2011-06-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. PMID:21376738

  14. [Advanced and Metastatic Lung Cancer – What is new in the Diagnosis and Therapy?].

    PubMed

    Rothschild, Sacha I

    2015-07-01

    Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided.

  15. Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

    ClinicalTrials.gov

    2016-06-17

    Bile Duct Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIA Small Intestinal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIB Small Intestinal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  16. Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  17. The p53-mediated cytotoxicity of photodynamic therapy of cancer: Recent advances

    SciTech Connect

    Zawacka-Pankau, Joanna Krachulec, Justyna Grulkowski, Ireneusz Bielawski, Krzysztof P. Selivanova, Galina

    2008-11-01

    Photodynamic therapy (PDT) is a promising modality for the treatment of both pre-malignant and malignant lesions. The mechanism of action converges mainly on the generation of reactive oxygen species which damage cancer cells directly as well as indirectly acting on tumor vasculature. The exact mechanism of PDT action is not fully understood, which is a formidable barrier to its successful clinical application. Elucidation of the mechanisms of cancer cell elimination by PDT might help in establishing highly specific, non-genotoxic anti-cancer treatment of tomorrow. One of the candidate PDT targets is the well-known tumor suppressor p53 protein recognized as the guardian of the genome. Together with its family members, p73 and p63 proteins, p53 is involved in apoptosis induction upon stress stimuli. The wild-type and mutant p53-targeting chemotherapeutics are currently extensively investigated as a promising strategy for highly specific anti-cancer therapy. In photodynamic therapy porphyrinogenic sensitizers are the most widely used compounds due to their potent biophysical and biochemical properties. Recent data suggest that the p53 tumor suppressor protein might play a significant role in porphyrin-PDT-mediated cell death by direct interaction with the drug which leads to its accumulation and induction of p53-dependent cell death both in the dark and upon irradiation. In this review we describe the available evidence on the role of p53 in PDT.

  18. Immunomicelles for advancing personalized therapy.

    PubMed

    Sawant, Rupa R; Jhaveri, Aditi M; Torchilin, Vladimir P

    2012-10-01

    Personalized medicine, which ultimately seeks to afford tailored therapeutic regimens for individual patients, is quickly emerging as a new paradigm in the diagnosis and treatment of diseases. The idea of casting aside generic treatments in favor of patient-centric therapies has become feasible owing to advances in nanotechnology and drug delivery coupled with an enhanced knowledge of genomics and an understanding of disease at the molecular level. This review highlights polymeric immunomicelles as a class of nanocarriers that have the potential to combine diagnosis, targeted drug therapy, as well as imaging and monitoring of therapeutic response, to render a personalized approach to the management of disease. Smart multi-functional immunomicelles, as the next generation of nanocarriers, are poised for facilitating personalized cancer treatment. This review provides an assessment of immunomicelles as tools for advancing personalized therapy of diseases, with cancer being the major focus. PMID:22917778

  19. Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

    PubMed

    Meko, J; Rusch, V W

    2000-10-01

    During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

  20. High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

    PubMed Central

    Wu, Feng

    2014-01-01

    The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound (HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer. PMID:25469016

  1. New Strategies for Multimodality Therapy in Treating Locally Advanced Cervix Cancer.

    PubMed

    Verma, Jonathan; Monk, Bradley J; Wolfson, Aaron H

    2016-10-01

    Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC. PMID:27619255

  2. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    PubMed

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia. PMID:27151773

  3. Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

    PubMed Central

    Houston, S J; Plunkett, T A; Barnes, D M; Smith, P; Rubens, R D; Miles, D W

    1999-01-01

    The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression (P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen (n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy. © 1999 Cancer Research Campaign PMID:10098763

  4. Advances in combination therapies based on nanoparticles for efficacious cancer treatment: an analytical report.

    PubMed

    Mignani, Serge; Bryszewska, Maria; Klajnert-Maculewicz, Barbara; Zablocka, Maria; Majoral, Jean-Pierre

    2015-01-12

    The main objective of nanomedicine research is the development of nanoparticles as drug delivery systems or drugs per se to tackle diseases as cancer, which are a leading cause of death with developed nations. Targeted treatments against solid tumors generally lead to dramatic regressions, but, unfortunately, the responses are often short-lived due to resistant cancer cells. In addition, one of the major challenges of combination drug therapy (called "cocktail") is the crucial optimization of different drug parameters. This issue can be solved using combination nanotherapy. Nanoparticles developed in oncology based on combination nanotherapy are either (a) those designed to combat multidrug resistance or (b) those used to circumvent resistance to clinical cancer drugs. This review provides an overview of the different nanoparticles currently used in clinical treatments in oncology. We analyze in detail the development of combinatorial nanoparticles including dendrimers for dual drug delivery via two strategic approaches: (a) use of chemotherapeutics and chemosensitizers to combat multidrug resistance and (b) use of multiple cytotoxic drugs. Finally, in this review, we discuss the challenges, clinical outlook, and perspectives of the nanoparticle-based combination therapy in cancer.

  5. Rethinking end-points for bone-targeted therapy in advanced cancer.

    PubMed

    Gómez García, Susana; Clemons, Mark; Amir, Eitan

    2016-08-01

    The principal objective for any medical therapy is to improve either the duration of life and/or its quality. Metastases in bone can lead to clinically defined events termed skeletal-related events (SREs) which are a quantifiable measure of skeletal morbidity. Avoidance and/or delay of SREs have become the principal objective in trials exploring the efficacy of bone-targeted therapy in patients with skeletal metastases. Despite reductions in the frequency or rate of SRE occurrence, trials of bone-targeted therapy have failed to show any effect on either progression-free or overall survival when compared with placebo or other bone-targeting agents. Similarly, trials of bone-targeted therapy have not shown consistent effects on quality of life. The validity of SRE-based primary outcome measures in cancer clinical trials is therefore, questionable. More novel end-point selection for trials of bone-targeted therapy seems warranted. Composite measures comprising occurrence of symptomatic skeletal events and patient reported outcomes may be an effective solution and warrants further investigation. PMID:27299662

  6. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy

    PubMed Central

    Zhao, Baozhong; He, Yu-Ying

    2011-01-01

    Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells. Recently, PDT has been widely used in treating non-melanoma skin malignancies, the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies. The topical ‘photosensitizers’ commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate, which are precursors of the endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl 5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases, which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis, basal cell carcinoma and squamous cell carcinoma. The most recent and promising developments in PDT include the discovery of new photosensitizers, the exploitation of new drug delivery systems and the combination of other modalities, which will all contribute to increasing PDT therapeutic efficacy and improving outcome. This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers, as well as recent developments and possible future research directions. PMID:21080805

  7. Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications.

    PubMed

    Beik, Jaber; Abed, Ziaeddin; Ghoreishi, Fatemeh S; Hosseini-Nami, Samira; Mehrzadi, Saeed; Shakeri-Zadeh, Ali; Kamrava, S Kamran

    2016-08-10

    In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia. PMID:27264551

  8. Genomic Alterations in Advanced Esophageal Cancer May Lead to Subtype-Specific Therapies

    PubMed Central

    Forde, Patrick M.

    2013-01-01

    The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8–12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease. PMID:23853247

  9. Genomic alterations in advanced esophageal cancer may lead to subtype-specific therapies.

    PubMed

    Forde, Patrick M; Kelly, Ronan J

    2013-01-01

    The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8-12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease.

  10. Molecular targeted therapies in advanced gastric cancer: does tumor histology matter?

    PubMed Central

    Wong, Hilda

    2013-01-01

    It is increasingly recognized that gastric cancer is a heterogeneous disease which may be divided into subgroups based on histological, anatomical, epidemiological and molecular classifications. Distinct molecular drivers and tumor biology, and thus different treatment targets and predictive biomarkers, may be implicated in each subtype. However, there is little evidence in the literature regarding the correlation among these different classifications, and particularly the molecular aberrations present in each subtype. In this review, we approach advanced gastric cancer (AGC) by presenting aberrant molecular pathways and their potential therapeutic targets in gastric cancer according to histological and anatomical classification, dividing gastric cancer into proximal nondiffuse, distal nondiffuse and diffuse disease. Several pathways are involved predominantly, although not exclusively, in different subtypes. This may help to explain the disappointing results of many published AGC trials in which study populations were heterogeneous regardless of clinicopathological characteristics of the primary tumor. Histological and anatomical classification may provide insights into tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic. However, some molecular pathways implicated in gastric cancer have not been studied in correlation with histological or anatomical subtypes. Further studies are necessary to confirm the suggestion that such classification may predict tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic. PMID:23320047

  11. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  12. Current targeted therapies in the treatment of advanced colorectal cancer: a review

    PubMed Central

    Moriarity, Andrew; O’Sullivan, Jacintha; Kennedy, John; Mehigan, Brian; McCormick, Paul

    2016-01-01

    Treatment strategies for metastatic colorectal cancer (mCRC) patients have undergone dramatic changes in the past decade and despite improved patient outcomes, there still exist areas for continued development. The introduction of targeted agents has provided clinicians with additional treatment options in mCRC, however, results have been mixed at best. These novel therapies were designed to interfere with specific molecules involved in the cellular carcinogenesis pathway and ultimately deliver a more focused treatment. Currently, their use in mCRC has been limited primarily as an adjunct to conventional chemotherapy regimens. This review explores the relevant cell-signaling networks in colorectal cancer, provides focus on the current targeted agent armamentarium approved for use in mCRC and explores the usefulness of predictive mCRC biomarkers. PMID:27482287

  13. Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced Pancreatic Cancer

    PubMed Central

    Durante, Marco; Tommasino, Francesco; Yamada, Shigeru

    2015-01-01

    Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumor hypoxia. Combination with chemotherapy improves the overall survival (OS). We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease. PMID:26217585

  14. Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2014-09-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer

  15. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies.

    PubMed

    Jafri, Mohammad A; Ansari, Shakeel A; Alqahtani, Mohammed H; Shay, Jerry W

    2016-01-01

    Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase assembly, intracellular trafficking and recruitment to telomeres for completing DNA synthesis, which may provide novel targets for the development of anticancer agents. Here, we summarize telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of telomerase inhibitors, as well as potential novel targets, will be summarized. PMID:27323951

  16. Therapy for advanced thyroid cancer: treatment of a high risk case.

    PubMed

    Ceriati, F; Cavicchioni, C; Logroscino, C; Pastore, G; Montemaggi, P; Fabiano, A; Mantovani, M; Marino, I R; Ardito, G; De Luca, G

    1987-01-01

    The treatment of a high risk case of an advanced thyroid cancer is reported. The patient had a thyroid cancer with metastatic lesions of the frontal bone, left temporal bone, left sacroiliac joint, lytic destruction of C6 and lytic lesion of C7. A pre-operative immobilization of the cervical spine was performed by a halo cast set on a corset of gypsum. After this, the patient underwent a thyroidectomy and, at the same time, a metallic plate was applied to immobilize C5-C7. A month after he underwent reoperative surgery to stabilize definitively the cervical spine. Subsequently he was treated by TCT and 131I subdivided in several cycles. The latest total body scan demonstrated a complete regression of secondary lesions.

  17. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  18. Advances of Targeted Therapy in Treatment of Unresectable Metastatic Colorectal Cancer

    PubMed Central

    Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review. PMID:27127793

  19. Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  20. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    PubMed Central

    Cuaron, John J.; Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David; Ho, Alice; Powell, Simon; Hug, Eugen; Cahlon, Oren

    2016-01-01

    Purpose To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n = 28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01–3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%–30.3%). The median contralateral lung V5 was 0.34% (range, 0%–5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0–65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03–3.50 Gy (RBE)]. Conclusions Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  1. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    SciTech Connect

    Cuaron, John J.; Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David; Ho, Alice; Powell, Simon; Hug, Eugen; Cahlon, Oren

    2015-06-01

    Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  2. [Examination of the safety of docetaxel/cyclophosphamide combination therapy for advanced recurrent breast cancer].

    PubMed

    Yoneyama, Kimiyasu; Koshida, Yoshitomo; Toriumi, Fumiki; Murayama, Takaya; Toeda, Hiroyuki; Imazu, Yoshihiro; Motegi, Katsuhiko; Akamatsu, Hidetoshi; Ohyama, Renpei

    2006-10-01

    In the treatment of recurrent breast cancer in patients previously treated with anthracycline drugs, taxane drugs are generally used. This time, we retrospectively studied the safety of docetaxel/cyclophosphamide combination therapy (hereinafter referred to as TC therapy). Ten patients (mean age: 52.8 years old) were included in the study. Metastatic/recurrent sites included 3 skin, 2 each of contralateral breast, lung and bone, and 1 each of liver, carcinomatous pleurisy and supraclavicular lymph node. Seven patients had a history of anthracycline treatment. The patients received TC at doses of 60 mg/m(2) and 500 mg/m(2), respectively, every 3 weeks. With regard to adverse events, non-hematotoxic events included alopecia in all the patients, generalized malaise in 5, and abnormal nail in 1. Hematotoxic events were grades 2 and 3 decreased neutrophil count in 5 patients. One patient had grade 4 pyrexia associated with oral candida. The patient was admitted and treated with fluid replacement and granulocyte colony-stimulating factor (G-CSF). There were no other patients in whom the treatment was prolonged or dosage was reduced due to adverse reactions. TC therapy is considered to be a beneficial treatment method in terms of safety since it can be instituted on an outpatient basis. PMID:17033252

  3. Advances in Therapeutic Cancer Vaccines.

    PubMed

    Wong, Karrie K; Li, WeiWei Aileen; Mooney, David J; Dranoff, Glenn

    2016-01-01

    Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines. PMID:26923002

  4. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer1

    PubMed Central

    Shibata, Tatsuhiro; Kokubu, Akiko; Saito, Shigeru; Narisawa-Saito, Mako; Sasaki, Hiroki; Aoyagi, Kazuhiko; Yoshimatsu, Yuki; Tachimori, Yuji; Kushima, Ryoji; Kiyono, Tohru; Yamamoto, Masayuki

    2011-01-01

    Esophageal squamous cancer (ESC) is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT) has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22%) in advanced ESC tumors and ESC cell lines (3/10). The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT. PMID:21969819

  5. Advances in Computational Radiation Biophysics for Cancer Therapy: Simulating Nano-Scale Damage by Low-Energy Electrons

    NASA Astrophysics Data System (ADS)

    Kuncic, Zdenka

    Computational radiation biophysics is a rapidly growing area that is contributing, alongside new hardware technologies, to ongoing developments in cancer imaging and therapy. Recent advances in theoretical and computational modeling have enabled the simulation of discrete, event-by-event interactions of very low energy (≪ 100 eV) electrons with water in its liquid thermodynamic phase. This represents a significant advance in our ability to investigate the initial stages of radiation induced biological damage at the molecular level. Such studies are important for the development of novel cancer treatment strategies, an example of which is given by microbeam radiation therapy (MRT). Here, new results are shown demonstrating that when excitations and ionizations are resolved down to nano-scales, their distribution extends well outside the primary microbeam path, into regions that are not directly irradiated. This suggests that radiation dose alone is insufficient to fully quantify biological damage. These results also suggest that the radiation cross-fire may be an important clue to understanding the different observed responses of healthy cells and tumor cells to MRT.

  6. Advances in Computational Radiation Biophysics for Cancer Therapy: Simulating Nano-Scale Damage by Low-Energy Electrons

    NASA Astrophysics Data System (ADS)

    Kuncic, Zdenka

    2015-10-01

    Computational radiation biophysics is a rapidly growing area that is contributing, alongside new hardware technologies, to ongoing developments in cancer imaging and therapy. Recent advances in theoretical and computational modeling have enabled the simulation of discrete, event-by-event interactions of very low energy (≪ 100 eV) electrons with water in its liquid thermodynamic phase. This represents a significant advance in our ability to investigate the initial stages of radiation induced biological damage at the molecular level. Such studies are important for the development of novel cancer treatment strategies, an example of which is given by microbeam radiation therapy (MRT). Here, new results are shown demonstrating that when excitations and ionizations are resolved down to nano-scales, their distribution extends well outside the primary microbeam path, into regions that are not directly irradiated. This suggests that radiation dose alone is insufficient to fully quantify biological damage. These results also suggest that the radiation cross-fire may be an important clue to understanding the different observed responses of healthy cells and tumor cells to MRT.

  7. Targeted therapies for cancer

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000902.htm Targeted therapies for cancer To use the sharing features on ... cells so they cannot spread. How Does Targeted Therapy Work? Targeted therapy drugs work in a few ...

  8. [Breast cancer. Individualized therapy concepts].

    PubMed

    Harbeck, N; Wuerstlein, R

    2013-02-01

    Personalized medicine in the sense of individualized therapy concepts plays an important role in breast cancer. In early breast cancer the molecular subtypes luminal A and B and basal-like are important for planning adjuvant systemic therapy. Prognostic and predictive markers, such as hormone receptor status, HER2, Ki-67, uPA/PAI-1 or multiple gene tests, such as Oncotype DX® currently allow avoidance of an over therapy or under therapy. In early and also advanced breast cancer there are an increasing number of new targeted therapies which represent an augmentation of standard endocrine and chemotherapy and in the future could at least partially replace them. As a whole the therapy regimens for breast cancer have become more complex due to the inclusion of molecular information, new therapies and the withdrawal of conventional treatment concepts. Decisive for the future will be the confirmation of this development by modern study concepts contemporarily with adequate evidence. It could then be expected that a personalized therapy for early breast cancer and in particular adjuvant chemotherapy would only be used for those patients for whom it is really necessary. In advanced stage disease there is justified hope that the survival time in the sense of a chronic disease can be improved by the use of targeted therapy.

  9. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

    SciTech Connect

    Kumar, Rachit; Wild, Aaron T.; Ziegler, Mark A.; Hooker, Ted K.; Dah, Samson D.; Tran, Phuoc T.; Kang, Jun; Smith, Koren; Zeng, Jing; Pawlik, Timothy M.; Tryggestad, Erik; Ford, Eric; Herman, Joseph M.

    2013-10-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D{sub max} of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D{sub mean}, D{sub max}, D{sub 1cc}, D{sub 4%}, and V{sub 20} {sub Gy} compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V{sub 95%} (p = 0.01) and D{sub mean} (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at

  10. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: a dosimetric analysis.

    PubMed

    Kumar, Rachit; Wild, Aaron T; Ziegler, Mark A; Hooker, Ted K; Dah, Samson D; Tran, Phuoc T; Kang, Jun; Smith, Koren; Zeng, Jing; Pawlik, Timothy M; Tryggestad, Erik; Ford, Eric; Herman, Joseph M

    2013-01-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non-duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal Dmax of<30Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal Dmean, Dmax, D1cc, D4%, and V20Gy compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V95% (p = 0.01) and Dmean (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at risk, whereas for IMRT it is compromised target coverage

  11. Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

    SciTech Connect

    Weiss, Elisabeth; Fatyga, Mirek; Wu, Yan; Dogan, Nesrin; Balik, Salim; Sleeman, William; Hugo, Geoffrey

    2013-07-01

    Purpose: To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Methods and Materials: Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). Results: The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. Conclusions: The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

  12. Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

    NASA Astrophysics Data System (ADS)

    Sztejnberg Goncalves-Carralves, Manuel Leonardo

    This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients' images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT

  13. Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With Bevacizumab

    ClinicalTrials.gov

    2016-03-14

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  14. Current advances in biomarkers for targeted therapy in triple-negative breast cancer

    PubMed Central

    Fleisher, Brett; Clarke, Charlotte; Ait-Oudhia, Sihem

    2016-01-01

    Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD) and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-8); cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the gluco-corticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC. PMID:27785100

  15. Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers.

    PubMed

    Eng, Juliana; Hsu, Meier; Chaft, Jamie E; Kris, Mark G; Arcila, Maria E; Li, Bob T

    2016-09-01

    Human epidermal growth factor receptor 2 (HER2, ERBB2) mutations occur in 3% of lung adenocarcinomas. While case reports and series have shown activity of HER2 targeted agents in these patients, little is known about outcomes of chemotherapies. Patients with stage IV HER2-mutant lung cancers at Memorial Sloan Kettering were reviewed. Patient demographics, types of HER2 mutations, duration of systemic treatments and survival were analyzed. We identified 38 patients with HER2-mutant lung cancers: median age 62; majority were women (n=24), never smokers (n=22), and all had adenocarcinomas. A 12 base pair in-frame insertion YVMA in exon 20 (p.A775_G776insYVMA) was present in 24 (63%, 95% CI 46-78%) patients. In addition, there were four 9 base pair insertions, one 6 base pair insertion, and five 3 base pair insertions in exon 20, and four single bp substitutions (exon 20 L755F, V777L, D769H, exon 8 S310F). The median overall survival from date of diagnosis of stage IV disease was 2.3 years (95% CI 1.2-2.6). The median duration of chemotherapy was 4.3 months (68 treatments, range 0-21 months): 6.2 months for pemetrexed ±platinum/bevacizumab, 4 months for taxane ±platinum/bevacizumab, 2.6 months for gemcitabine, 3.5 months for vinorelbine. The median duration of HER2 tyrosine kinase inhibitors was 2.2 months (28 treatments, range 0.3-16.3 months). As we search for better targeted therapies for patients with HER2-mutant lung cancers, chemotherapy remains an important component of care. PMID:27565914

  16. [A case of advanced esophageal cancer with direct bronchial invasion successfully treated by multidisciplinary therapy].

    PubMed

    Haba, Yusuke; Okamoto, Koichi; Watanabe, Toshifumi; Tsukada, Tomoya; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Oyama, Katsunobu; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Ohta, Tetsuo

    2014-11-01

    A 66-year-old man with advanced esophageal cancer (staging Mt, 6.0 cm, cT3N0M0, cStage II) was administered neoadjuvant chemotherapy (NAC: 5-fluorouracil and cisplatin). As the tumor continued to grow after one course of NAC, video-assisted thoracoscopic surgery(VATS) was used to perform an esophagectomy along with 3-field lymph node dissection and retrosternal route reconstruction using a gastric tube. The second course of NAC was not administered. Intraoperative findings showed the direct invasion of the primary esophageal cancer into the membranous portion of the left bronchus. The maximum possible tumor tissue was resected and removed. The tumor tissue was exposed extensively to the surface of the esophageal adventitia and a residual tumor at the surface of the left bronchus was suspected. It was diagnosed as CT-pT4 (left bronchus), N0, M0, CT-pStage III. Subsequently, we administered chemoradiotherapy consisting of weekly low-dose docetaxel with radiation for the residual tumor (60 Gy/30 Fr). The patient is still alive 40 months after surgery without any signs of recurrence.

  17. [A case of advanced esophageal cancer with direct bronchial invasion successfully treated by multidisciplinary therapy].

    PubMed

    Haba, Yusuke; Okamoto, Koichi; Watanabe, Toshifumi; Tsukada, Tomoya; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Oyama, Katsunobu; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Ohta, Tetsuo

    2014-11-01

    A 66-year-old man with advanced esophageal cancer (staging Mt, 6.0 cm, cT3N0M0, cStage II) was administered neoadjuvant chemotherapy (NAC: 5-fluorouracil and cisplatin). As the tumor continued to grow after one course of NAC, video-assisted thoracoscopic surgery(VATS) was used to perform an esophagectomy along with 3-field lymph node dissection and retrosternal route reconstruction using a gastric tube. The second course of NAC was not administered. Intraoperative findings showed the direct invasion of the primary esophageal cancer into the membranous portion of the left bronchus. The maximum possible tumor tissue was resected and removed. The tumor tissue was exposed extensively to the surface of the esophageal adventitia and a residual tumor at the surface of the left bronchus was suspected. It was diagnosed as CT-pT4 (left bronchus), N0, M0, CT-pStage III. Subsequently, we administered chemoradiotherapy consisting of weekly low-dose docetaxel with radiation for the residual tumor (60 Gy/30 Fr). The patient is still alive 40 months after surgery without any signs of recurrence. PMID:25731408

  18. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  19. Case-Matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer

    SciTech Connect

    Fletcher, Sophie G.; Mills, Stacey E.; Smolkin, Mark E.; Theodorescu, Dan . E-mail: dt9d@virginia.edu

    2006-11-15

    Purpose: Few studies critically compare current radiotherapy techniques to surgery for patients with locally advanced prostate cancer, despite an urgent need to determine which approach offers superior cancer control. Our objective was to compare rates of biochemical relapse-free survival (BFS) and surrogates of disease specific survival among men with high risk adenocarcinoma of the prostate as a function of treatment modality. Methods and Materials: Retrospective data from 409 men with prostate-specific antigen (PSA) {>=}10 or Gleason 7-10 or Stage {>=}T2b cancer treated uniformly at one university between March 1988 and December 2000 were analyzed. Patients had undergone radical prostatectomy (RP), brachytherapy implant alone (BTM), or external beam radiotherapy with brachytherapy boost with short-term neoadjuvant and adjuvant androgen deprivation therapy (BTC). From the total study population a 1:1 matched-cohort analysis (208 patients matched via prostate-specific antigen, Gleason score) comparing RP with BTC was performed as well. Results: Estimated 4-year BFS rates were superior for patients treated with BTC (BTC 72%, BTM 25%, RP 53%; p < 0.001). Matched analysis of BTC vs. RP confirmed these results (BTC 73%, BTM 55%; p = 0.010). Relative risk (RR) of biochemical relapse for BTM and BTC compared with RP were 2.92 (1.95-4.36) and 0.56 (0.36-0.87) (p < 0.001, p = 0.010). RR for BTC from the matched cohort analysis was 0.44 (0.26-0.74; p = 0.002). Conclusions: High-risk prostate cancer patients receiving multimodality radiation therapy (BTC) display apparently superior BFS compared with those receiving surgery (RP) or brachytherapy alone (BTM)

  20. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  1. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    PubMed

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

  2. Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

    PubMed

    O'Neill, Daniel; Jones, Dominic; Wade, Mark; Grey, James; Nakjang, Sirintra; Guo, Wenrui; Cork, David; Davies, Barry R; Wedge, Steve R; Robson, Craig N; Gaughan, Luke

    2015-09-22

    The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated AR(W741L/C) mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of AR(W741L) highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, AR(W741L) transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients.

  3. Hormone Therapy for Breast Cancer

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Hormone Therapy for Breast Cancer On This Page What are hormones? How do ... sensitive breast cancer: Adjuvant therapy for early-stage breast cancer : Research has shown that women treated for early- ...

  4. 177Lu-labeled Gold Nanoparticles for Radiation Therapy of Locally Advanced Breast Cancer

    NASA Astrophysics Data System (ADS)

    Yook, Simmyung

    Locally advanced breast cancer (LABC) occurs in about 10-15% of patients diagnosed with breast cancer (BC) and 30% of these patients have triple negative breast cancer (TNBC) that are often epidermal growth factor receptor (EGFR)-positive. The goal of the proposed research was design and evaluate preclinically a novel radiation nanomedicine for LABC composed of EGFR-targeted gold nanoparticles (AuNP) by covalently conjugating panitumumab and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexing 177Lu incorporated into a metal-chelating polymer (MCP) (177 Lu-T-AuNP) which could be used as a neoadjuvant treatment to improve the outcome of patients with LABC. 177Lu-T-AuNP were efficiently internalized by EGFR-positive BC cells and were significantly more effective than 177Lu-labeled and non-targeted (NT)-AuNP for killing these cells. For radiation treatment of EGFR-positive tumours, both 177Lu-T-AuNP and 177Lu-NT-AuNP were intratumourally (i.t.) injected into athymic mice with MDA-MB-468 BC xenografts for comparison. Biodistribution studies showed that 177Lu-T-AuNPs exhibited 2-fold higher tumour retention than 177Lu-NT-AuNPs following i.t. injection at 48 h p.i. Both forms of radiolabeled AuNP were highly effective for inhibiting tumour growth without normal organ toxicity due to local tumour retention of both form of AuNP. To minimize the displacement of 177Lu-labeled MCP from AuNP, polyethylene glycol (PEG) ligands presenting a disulfide [ 177Lu-DOTA-PEG-ortho-pyridyl disulfide (OPSS)], a lipoic acid (LA) [177Lu-DOTA-PEG-lipoic acid (LA)] or multi-LA [PEG- pGlu(177Lu-DOTA)8-LA4] for multivalent binding were synthesized and the stability of MCP-AuNP complexes determined. In vitro challenge study with thiol-containing molecules or human plasma, PEG-pGlu(DOTA)8-LA4-AuNP were most stable. In whole body elimination study, elimination of radioactivity due to displacement of 177Lu-MCP from AuNP in mice injected with 177Lu-DOTA-PEG-OPSS-AuNP was more

  5. Noteworthy clinical case studies in cancer gene therapy: tumor-targeted Rexin-G advances as an efficacious anti-cancer agent.

    PubMed

    Gordon, Erlinda M; Hall, Frederick L

    2010-06-01

    The advent of pathotropic (disease-seeking) targeting technology has ushered cancer gene therapy across the threshold of history, marking the beginning of a new epoch of medical praxis. For the first time, clinical oncologists can reach beyond the finest of catheters, beyond the reach of the most gifted surgeons, to the very fabric of metastatic disease in an effort to halt the progression and turn the tide of otherwise intractable cancers. The enabling molecular biotechnologies embodied in the leading tumor-targeted agent, Rexin-G, and its timely development as a safe and effective anti-cancer drug - from oncogene discovery and target validation, to molecular engineering of the core nanotechnologies, to the first clinical proofs-of principle, confirmatory trials, expanded access programs, and accelerated regulatory approvals - have been extensively documented in the medical literature. Therefore, this paper represents a final chapter, highlighting a series of noteworthy cases studies in the emergent field of targeted genetic medicine: case studies which, in and of themselves, reveal vital and important aspects of the molecular-genetic bio-pharmacology, advanced clinical protocols, refinement of patient monitoring, expanding treatment options, and strategic medical approaches to patient care that exemplify and thereby extend the established principles of pathotropic targeting and cancer gene therapy to a new generation of clinical practitioners.

  6. NANOTECHNOLOGY IN CANCER THERAPY

    PubMed Central

    Aslan, Burcu; Ozpolat, Bulent; Sood, Anil K.; Lopez-Berestein, Gabriel

    2014-01-01

    Cancer is one of the major causes of mortality worldwide and advanced techniques for therapy are urgently needed. The development of novel nanomaterials and nanocarriers has allowed a major drive to improve drug delivery in cancer. The major aim of most nanocarrier applications has been to protect the drug from rapid degradation after systemic delivery and allowing it to reach tumor site at therapeutic concentrations, meanwhile avoiding drug delivery to normal sites as much as possible to reduce adverse effects. These nanocarriers are formulated to deliver drugs either by passive targeting, taking advantage of leaky tumor vasculature or by active targeting using ligands that increase tumoral uptake potentially resulting in enhanced antitumor efficacy, thus achieving a net improvement in therapeutic index. The rational design of nanoparticles plays a critical role since structural and physical characteristics, such as size, charge, shape, and surface characteristics determine the biodistribution, pharmacokinetics, internalization and safety of the drugs. In this review, we focus on several novel and improved strategies in nanocarrier design for cancer therapy. PMID:24079419

  7. Radiation Therapy for Cancer

    MedlinePlus

    ... What is radiation therapy? Radiation therapy uses high-energy radiation to shrink tumors and kill cancer cells ( ... is a measure of the amount of radiation energy absorbed by 1 kilogram of human tissue. Different ...

  8. Evidence-based recommendations on androgen deprivation therapy for localized and advanced prostate cancer

    PubMed Central

    Belsey, Jonathan; Drewa, Tomasz; Kołodziej, Anna; Skoneczna, Iwona; Milecki, Piotr; Dobruch, Jakub; Słojewski, Marcin; Chłosta, Piotr L.

    2016-01-01

    Introduction The management of prostate cancer (PC) is still evolving. Although, androgen deprivation therapy (ADT) is an established treatment option, particularly in patients with disseminated disease, important data regarding hormonal manipulation have recently emerged. The aim of this paper is to review the evidence on ADT, make recommendations and address areas of controversy associated with its use in men with PC. Material and methods An expert panel was convened. Areas related to the hormonal management of patients with PC requiring evidence review were identified and questions to be addressed by the panel were determined. Appropriate literature review was performed and included a search of online databases, bibliographic reviews and consultation with experts. Results The panel was able to provide recommendations on: 1) which patients with localised PC should receive androgen deprivation in conjunction with radiotherapy (RT); 2) what standard initial treatment should be used in metastatic hormone-naïve PC (MHNPC); 3) efficacy of androgen deprivation agents; 4) whether ADT should be continued in patients with castration resistant PC (CRPC). However, no recommendations could be made for combined ADT and very high-dose RT in patients with an intermediate-risk disease. Conclusions ADT remains the cornerstone of treatment for both metastatic hormone-naïve and castration-resistant PC. According to the expert panel's opinion, based on the ERG report, luteinizing hormone-releasing hormone agonists might not be equivalent but this needs to be confirmed in long-term data. The combined use of ADT and RT improves outcome and survival in men with high-risk localised disease. The benefits in patients with intermediate-risk disease, particularly those subject to escalated dose RT are controversial. PMID:27551549

  9. Long-term Oncologic Outcome Following Preoperative Combined Modality Therapy and Total Mesorectal Excision of Locally Advanced Rectal Cancer

    PubMed Central

    Guillem, Jose G.; Chessin, David B.; Cohen, Alfred M.; Shia, Jinru; Mazumdar, Madhu; Enker, Warren; Paty, Philip B.; Weiser, Martin R.; Klimstra, David; Saltz, Leonard; Minsky, Bruce D.; Wong, W Douglas

    2005-01-01

    Objective: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. Summary Background Data: Locally advanced (T3–4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. Methods: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6cm from the anal verge (range 0–15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. Results: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). Conclusions: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study. PMID:15849519

  10. Locally advanced breast cancer made amenable to radical surgery after a combination of systemic therapy and Mohs paste: two case reports

    PubMed Central

    2012-01-01

    Introduction Chemotherapy and other systemic therapies are the primary treatments for patients with unresectable, locally advanced breast cancer. The clinical application of supportive care using Mohs paste has become widespread for the purpose of improving patients’ quality of life. Here, we report two cases of locally advanced breast cancer, for which the patients underwent radical surgery after a combination of systemic therapy and Mohs chemosurgery. Case presentations Patient 1 was a 90-year-old Japanese woman with right breast cancer diagnosed as stage IIIB (T4bN1M0). The treatment included Mohs paste application and hormonal therapies. Patient 2 was a 60-year-old Japanese woman with right breast cancer diagnosed as stage IIIB (T4cN2aM0). Her treatment included Mohs paste application, together with chemotherapy (four cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, and four cycles of docetaxel). In both cases, a reduction in the primary tumor volume was observed, and radical mastectomy and axillary lymph node dissection were possible without relaxation incision or skin flap. Conclusion We report patients with no distant metastases who were able to undergo radical resection after a combination of systemic therapy and Mohs chemosurgery. For locally advanced breast cancer, Mohs chemosurgery, in addition to multidisciplinary treatment, is useful. PMID:23095125

  11. Comparative effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in advanced gastric cancer: A meta-analysis of randomized controlled trials

    PubMed Central

    Zhu, Yanjie; Huang, Jiale; Liu, Yanna; Zhao, Liying; Li, Zhijia; Liu, Hao; Wang, Qi-long; Qi, Xiaolong

    2016-01-01

    Background & Aims Platinum-based drugs are the most significant chemotherapy for advanced gastric cancer. The study aims to compare the efficacy and safety of oxaliplatin-based therapy versus cisplatin-based therapy in patients with advanced gastric cancer. Materials and Methods An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in patients with advanced gastric cancer were eligible. The primary endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS). The second endpoint was the adverse events. Results Five phase II or III RCTs involving a total of 2,046 patients were identified. The results showed that there were no significant difference in ORR (OR = 1.17, 95% CI = 0.98–1.40, p = 0.08, I2 = 0%), PFS (HR = 0.92, 95% CI = 0.84–1.01, p = 0.09, I2 = 0%) and OS (HR = 0.91, 95% CI = 0.82–1.01, p = 0.07, I2 = 0%) between oxaliplatin-based therapy and cisplatin-based therapy. In addition, oxaliplatin-based therapy had lower risk of neutropenia, anemia, nausea, alopecia, thromboembolism, stomatitis and creatinine increased at all grades, and neutropenia, anemia, leukopenia and alopecia at 3–4 grades than cisplatin-based therapy. However, oxaliplatin-based therapy was associated with increased risk of neurosensory toxicity and thrombocytopenia. Conclusions Our meta-analysis showed that there were no significant difference in ORR, PFS and OS between oxaliplatin-based therapy and cisplatin-based therapy. The oxaliplatin-based therapy could generally decrease the risk of adverse effects except neurosensory toxicity and thrombocytopenia. PMID:27166187

  12. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    PubMed Central

    Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

    2015-01-01

    Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

  13. Long-term cancer-related fatigue outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with hormonal therapy

    PubMed Central

    Luo, Hua-Chun; Lei, Yong; Cheng, Hui-Hua; Fu, Zhi-Chao; Liao, Shao-Guang; Feng, Jing; Yin, Qin; Chen, Qun-Hua; Lin, Gui-Shan; Zhu, Jin-Feng; Xu, Jian-Feng; Wang, Dian

    2016-01-01

    Abstract The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F. In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy. PMID:27336890

  14. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

    Endometrial cancer is a common gynecologic malignancy typically diagnosed at early stage and cured with surgery alone. Adjuvant therapy is tailored according to the risk of recurrence, estimated based on the International Federation of Gynecology and Obstetrics (FIGO) stage and other histological factors. The objective of this manuscript is to review the evidence guiding adjuvant therapy for early stage and locally advanced uterine cancer. For patients with early stage disease, minimizing toxicity, while preserving outstanding cure rates remains the major goal. For patients with locally advanced endometrial cancer optimal combined regimens are being defined. Risk stratification based on molecular traits is under development and may aid refine the current risk prediction model and permit personalized approaches for women with endometrial cancer. PMID:24761218

  15. Biomarkers and targeted systemic therapies in advanced non-small cell lung cancer.

    PubMed

    Kumar, Mukesh; Ernani, Vinicius; Owonikoko, Taofeek K

    2015-11-01

    The last decade has witnessed significant growth in therapeutic options for patients diagnosed with lung cancer. This is due in major part to our improved technological ability to interrogate the genomics of cancer cells, which has enabled the development of biologically rational anticancer agents. The recognition that lung cancer is not a single disease entity dates back many decades to the histological subclassification of malignant neoplasms of the lung into subcategories of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). While SCLC continues to be regarded as a single histologic and therapeutic category, the NSCLC subset has undergone additional subcategorizations with distinct management algorithms for specific histologic and molecular subtypes. The defining characteristics of these NSCLC subtypes have evolved into important tools for prognosis and for predicting the likelihood of benefit when patients are treated with anticancer agents.

  16. [Neoadjuvant therapy in breast cancer].

    PubMed

    Ena, G

    2011-09-01

    Neoadjuvant treatment is the standard therapy for inflammatory and locally advanced breast cancer but is also applied in patients with primary operable breast cancer to facilitate breast-conserving surgery. Disease-free survival and overall survival are equivalent between patients treated with preoperative chemotherapy and patient receiving the same regimen postoperatively. Nevertheless, pathologic complete response can be a predictive indicator of long-term outcomes. Initially encompassing chemotherapy, it is actually extended to hormonotherapy for hormonoresponsive tumor and to targeted therapy such as trastuzumab for the HER2 positive tumor. The neoadjuvant approach of breast cancer will provide better understanding of breast cancer biology and promote translational research. In this paper, a review of the role of preoperative treatment in the management of breast cancer disease is discussed.

  17. Using economic analysis to evaluate the potential of multimodality therapy for elderly patients with locally advanced pancreatic cancer

    SciTech Connect

    Krzyzanowska, Monika K. . E-mail: monika.krzyzanowska@uhn.on.ca; Earle, Craig C.; Kuntz, Karen M.; Weeks, Jane C.

    2007-01-01

    Purpose: Development of new and expensive drugs with activity against pancreatic cancer has made economic considerations more relevant to treatment decision-making for advanced disease. Economic modeling can be used to explore the potential of such novel therapies and to inform clinical trial design. Methods and Materials: We developed a Markov model to evaluate the cost-effectiveness of radiation plus fluorouracil (RT-FU) relative to no treatment in elderly patients with locally advanced pancreatic cancer (LAPC) and to determine the economic potential of radiation plus gemcitabine (RT-GEM), a novel regimen for this disease. We used the SEER-Medicare database to estimate effectiveness and costs supplemented by data from the literature where necessary. Results: Relative to no treatment, RT-FU was associated with a cost-effectiveness ratio (ICER) of $68,724/QALY in the base case analysis. Compared with RT-FU, the ICER for RT-GEM was below $100,000/QALY when the risk of dying with the new regimen was <85% than with the standard regimen. However, >1,000 subjects would be necessary to demonstrate this level of efficacy in a randomized trial. The ICER of RT-GEM was most sensitive to utility values, and, at lower efficacy levels, to costs of gemcitabine and treatment-related toxicity. Conclusions: In elderly patients with LAPC, RT-FU is a cost-effective alternative to no treatment. The novel regimen of RT-GEM is likely to be cost-effective at any clinically meaningful benefit, but quality-of-life issues, drug acquisition, and toxicity-related costs may be relevant, especially at lower efficacy levels.

  18. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy

    PubMed Central

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-01-01

    Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC. A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria. Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ −8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) –8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS

  19. Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis

    PubMed Central

    Spratt, Daniel E.; Gordon Spratt, Elizabeth A.; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y.; Lacouture, Mario E.; Barker, Christopher A.

    2014-01-01

    Purpose To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. Methods MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I2 tests. Results After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Conclusion Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. PMID:25154827

  20. Neutron therapy of cancer

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.; Nellans, H. N.; Shaw, M. J.

    1969-01-01

    Reports relate applications of neutrons to the problem of cancer therapy. The biochemical and biophysical aspects of fast-neutron therapy, neutron-capture and neutron-conversion therapy with intermediate-range neutrons are presented. Also included is a computer program for neutron-gamma radiobiology.

  1. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    PubMed

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  2. Unproven (questionable) cancer therapies.

    PubMed Central

    Brigden, M L

    1995-01-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects of questionable therapies that make these treatments attractive to patients and that may be perceived as being deficient in the practice of conventional health care professionals. Physicians with patients with cancer should always make sure that unproven therapies are discussed early in the therapeutic relationship. They should also attempt to be aware of alternative therapies that are in vogue in their particular geographic area. PMID:8533410

  3. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    PubMed Central

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance. PMID:26310719

  4. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance.

    PubMed

    Jotte, Robert M; Spigel, David R

    2015-11-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance. PMID:26310719

  5. Advances in cancer control

    SciTech Connect

    Anderson, P.N. ); Engstrom, P.F. ); Mortenson, L.E. )

    1989-01-01

    This book contains the proceedings of the sixth annual meeting on Advances in Cancer Control. Included are the following articles: Barriers and facilitators to compliance with routine mammographic screening, Preliminary report of an intervention to improve mammography skills of radiologists.

  6. Bevacizumab, Fluorouracil, and Hydroxyurea Plus Radiation Therapy in Treating Patients With Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2013-02-06

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous

  7. Magnetic resonance imaging: A potential tool in assessing the addition of hyperthermia to neoadjuvant therapy in patients with locally advanced breast cancer

    PubMed Central

    CRACIUNESCU, OANA I.; THRALL, DONALD E.; VUJASKOVIC, ZELJKO; DEWHIRST, MARK W.

    2010-01-01

    The poor overall survival for patients with locally advanced breast cancers has led over the past decade to the introduction of numerous neoadjuvant combined therapy regimens to down-stage the disease before surgery. At the same time, more evidence suggests the need for treatment individualisation with a wide variety of new targets for cancer therapeutics and also multi modality therapies. In this context, early determination of whether the patient will fail to respond can enable the use of alternative therapies that can be more beneficial. The purpose of this review is to examine the potential role of magnetic resonance imaging (MRI) in early prediction of treatment response and prognosis of overall survival in locally advanced breast cancer patients enrolled on multi modality therapy trials that include hyperthermia. The material is organised with a review of dynamic contrast (DCE)-MRI and diffusion weighted (DW)-MRI for characterisation of phenomenological parameters of tumour physiology and their potential role in estimating therapy response. Most of the work published in this field has focused on responses to neoadjuvant chemotherapy regimens alone, so the emphasis will be there, however the available data that involves the addition of hyperthermia to the regimen will be discussed The review will also include future directions that include the potential use of MRI imaging techniques in establishing the role of hyperthermia alone in modifying breast tumour microenvironment, together with specific challenges related to performing such studies. PMID:20849258

  8. Proton therapy for cancer treatment.

    PubMed

    Dinesh Mayani, Devanshi

    2011-09-01

    Proton beam therapy is the latest advancement in the treatment of various types of cancer. It is a precise form of radiotherapy. It uses a beam of protons to target the cancer cells and destroys them. It scores high on precision and effectiveness when compared to other conventional cancer treatments like surgery, chemotherapy and xray radiotherapy. Proton beam therapy destroys the cancerous cells without harming the healthy cells. Thus it considerably reduces the side-effects that accompany conventional cancer treatments. Supporters say the technology allows physicians to treat a broad spectrum of cancers with few adverse effects, while more precisely targeting tumor cells with higher doses of radiation. Detractors say proton beam therapy is hugely expensive and has not been shown to be superior to conventional radiation treatment. With proton beam therapy, physicians use a cyclotron to accelerate protons and fire them directly into tumor cells with submillimeter precision. Because healthy tissue is largely spared, oncologists can, in theory, deliver much higher doses of radiation, while improving local control and reducing the risk for recurrence and morbidities.

  9. Multicriteria Optimization in Intensity-Modulated Radiation Therapy Treatment Planning for Locally Advanced Cancer of the Pancreatic Head

    SciTech Connect

    Hong, Theodore S. Craft, David L.; Carlsson, Fredrik; Bortfeld, Thomas R.

    2008-11-15

    Purpose: Intensity-modulated radiation therapy (IMRT) affords the potential to decrease radiation therapy-associated toxicity by creating highly conformal dose distributions. However, the inverse planning process can create a suboptimal plan despite meeting all constraints. Multicriteria optimization (MCO) may reduce the time-consuming iteration loop necessary to develop a satisfactory plan while providing information regarding trade-offs between different treatment planning goals. In this exploratory study, we examine the feasibility and utility of MCO in physician plan selection in patients with locally advanced pancreatic cancer (LAPC). Methods and Materials: The first 10 consecutive patients with LAPC treated with IMRT were evaluated. A database of plans (Pareto surface) was created that met the inverse planning goals. The physician then navigated to an 'optimal' plan from the point on the Pareto surface at which kidney dose was minimized. Results: Pareto surfaces were created for all 10 patients. A physician was able to select a plan from the Pareto surface within 10 minutes for all cases. Compared with the original (treated) IMRT plans, the plan selected from the Pareto surface had a lower stomach mean dose in 9 of 10 patients, although often at the expense of higher kidney dose than with the treated plan. Conclusion: The MCO is feasible in patients with LAPC and allows the physician to choose a satisfactory plan quickly. Generally, when given the opportunity, the physician will choose a plan with a lower stomach dose. The MCO enables a physician to provide greater active clinical input into the IMRT planning process.

  10. Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

    SciTech Connect

    Chiorean, E. Gabriela; Schneider, Bryan P.; Akisik, Fatih M.; Perkins, Susan M.; Anderson, Stephen; Johnson, Cynthia S.; DeWitt, John; Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John; Deluca, Jill; Bu, Guixue; Shahda, Safi; Loehrer, Patrick J.; Sandrasegaran, Kumar; Cardenes, Higinia R.

    2014-06-01

    Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m{sup 2} intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m{sup 2} intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K{sup trans} in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival.

  11. Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2014-06-05

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  12. Recent advances in multifunctional silica-based hybrid nanocarriers for bioimaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    Lim, Wei Qi; Phua, Soo Zeng Fiona; Xu, Hesheng Victor; Sreejith, Sivaramapanicker; Zhao, Yanli

    2016-06-01

    In recent years, there has been a considerable research focus on integrating cancer cell imaging and therapeutic functions into single nanoscale platforms for better treatment of cancer. This task could often be achieved by incorporating multiple components into a hybrid nanosystem. In this minireview, we highlight different types of silica-based hybrid nanosystems and their recent applications as integrated multifunctional platforms for cancer imaging and treatment. The discussions are divided into several sections focusing on various types of materials employed to integrate with silica, which include silica-metallic nanoparticle based hybrid nanocarriers, silica-gold nanoparticle based hybrid nanocarriers, silica-quantum dot based hybrid nanocarriers, silica-upconversion nanoparticle based hybrid nanocarriers, silica-carbon based hybrid nanocarriers, and organosilica nanocarriers. Therapeutic agents loaded in such hybrids include chemodrugs, proteins, DNA/RNA and photosensitizers. For targeted delivery into tumor sites, targeting ligands such as antibodies, peptides, aptamers, and other small molecules are grafted on the surface of the nanocarriers. At the end of the review, a brief summary and research outlook are presented. This minireview aims to provide a quick update of recent research achievements in the field.

  13. Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies

    PubMed Central

    Kolch, Walter; Kholodenko, Boris N.; Ambrosi, Cristina De; Barla, Annalisa; Biganzoli, Elia M.; Nencioni, Alessio; Patrone, Franco; Ballestrero, Alberto; Zoppoli, Gabriele; Verri, Alessandro; Parodi, Silvio

    2015-01-01

    The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis. We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions. Starting from an initial “physiologic condition”, the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model. Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal. PMID:25671297

  14. Advancing cancer drug discovery towards more agile development of targeted combination therapies.

    PubMed

    Carragher, Neil O; Unciti-Broceta, Asier; Cameron, David A

    2012-01-01

    Current drug-discovery strategies are typically 'target-centric' and are based upon high-throughput screening of large chemical libraries against nominated targets and a selection of lead compounds with optimized 'on-target' potency and selectivity profiles. However, high attrition of targeted agents in clinical development suggest that combinations of targeted agents will be most effective in treating solid tumors if the biological networks that permit cancer cells to subvert monotherapies are identified and retargeted. Conventional drug-discovery and development strategies are suboptimal for the rational design and development of novel drug combinations. In this article, we highlight a series of emerging technologies supporting a less reductionist, more agile, drug-discovery and development approach for the rational design, validation, prioritization and clinical development of novel drug combinations.

  15. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer

    PubMed Central

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas HG

    2011-01-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician’s discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account. PMID:22263071

  16. A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?

    PubMed Central

    Ciliberto, Domenico; Staropoli, Nicoletta; Caglioti, Francesca; Gualtieri, Simona; Fiorillo, Lucia; Chiellino, Silvia; De Angelis, Antonina Maria; Mendicino, Francesco; Botta, Cirino; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2015-01-01

    Summary It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005–2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655–0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847–1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722–0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents. PMID:26061272

  17. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    PubMed Central

    MOMOZONO, HIROYUKI; MIYAKE, HIDEAKI; TEI, HIROMOTO; HARADA, KEN-ICHI; FUJISAWA, MASATO

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC. PMID:27123292

  18. Tumor heterogeneity and resistance to EGFR-targeted therapy in advanced nonsmall cell lung cancer: challenges and perspectives

    PubMed Central

    Cheng, Xinghua; Chen, Haiquan

    2014-01-01

    Lung cancer, mostly nonsmall cell lung cancer, continues to be the leading cause of cancer-related death worldwide. With the development of tyrosine kinase inhibitors that selectively target lung cancer-related epidermal growth factor receptor mutations, management of advanced nonsmall cell lung cancer has been greatly transformed. Improvements in progression-free survival and life quality of the patients were observed in numerous clinical studies. However, overall survival is not prolonged because of later-acquired drug resistance. Recent studies reveal a heterogeneous subclonal architecture of lung cancer, so it is speculated that the tumor may rapidly adapt to environmental changes via a Darwinian selection mechanism. In this review, we aim to provide an overview of both spatial and temporal tumor heterogeneity as potential mechanisms underlying epidermal growth factor receptor tyrosine kinase inhibitor resistance in nonsmall cell lung cancer and summarize the possible origins of tumor heterogeneity covering theories of cancer stem cells and clonal evolution, as well as genomic instability and epigenetic aberrations in lung cancer. Moreover, investigational measures that overcome heterogeneity-associated drug resistance and new assays to improve tumor assessment are also discussed. PMID:25285017

  19. Combined therapy: surgery and intraoperative HDR brachytherapy for locally advanced and recurrent rectal cancer. Practical experience of Brachytherapy Department in Warsaw

    PubMed Central

    Radziszewski, Jakub; Lyczek, Jaroslaw; Kawczynska, Maria; Kulik, Anna

    2009-01-01

    Purpose Patients with locally advanced and recurrent rectal cancer have a dismal prognosis. The aim of proposed combined therapy – surgery and intraoperative brachytherapy, is to improve results of already applied methods and to define optimal group of patients for this treatment. We introduce practical experience of Brachytherapy Department in Cancer Centre – Institute in Warsaw. Material and methods Patients with primary T4NxM0 rectal cancer and isolated local pelvic recurrence were qualified for therapy. Between January 2005 and September 2008, 13 patients were included: 4 with primary cancer and 9 with recurrence, median age of 56. After surgical resection intraoperative radiotherapy was delivered with boost of high dose rate brachytherapy of 20Gy dose to the tumor bed. Results Primary point of the study is to evaluate impact of applied therapy on local control (LC), overall survival (OS) and disease free survival (DFS). Median follow-up is 16 months. Four of the patients died and 3 survivors are disease-free. There was no case of perioperative mortality. Conclusions A multimodality approach, using surgical resection with intra operative brachytherapy improves local control as well as patients survival in comparison with historical treatment group. Combined therapy is related to high morbidity, but low mortality. The preliminary observations seem to correspond with other authors data.

  20. Comparative study of four advanced 3d-conformal radiation therapy treatment planning techniques for head and neck cancer.

    PubMed

    Herrassi, Mohamed Yassine; Bentayeb, Farida; Malisan, Maria Rosa

    2013-04-01

    For the head-and-neck cancer bilateral irradiation, intensity-modulated radiation therapy (IMRT) is the most reported technique as it enables both target dose coverage and organ-at-risk (OAR) sparing. However, during the last 20 years, three-dimensional conformal radiotherapy (3DCRT) techniques have been introduced, which are tailored to improve the classic shrinking field technique, as regards both planning target volume (PTV) dose conformality and sparing of OAR's, such as parotid glands and spinal cord. In this study, we tested experimentally in a sample of 13 patients, four of these advanced 3DCRT techniques, all using photon beams only and a unique isocentre, namely Bellinzona, Forward-Planned Multisegments (FPMS), ConPas, and field-in-field (FIF) techniques. Statistical analysis of the main dosimetric parameters of PTV and OAR's DVH's as well as of homogeneity and conformity indexes was carried out in order to compare the performance of each technique. The results show that the PTV dose coverage is adequate for all the techniques, with the FPMS techniques providing the highest value for D95%; on the other hand, the best sparing of parotid glands is achieved using the FIF and ConPas techniques, with a mean dose of 26 Gy to parotid glands for a PTV prescription dose of 54 Gy. After taking into account both PTV coverage and parotid sparing, the best global performance was achieved by the FIF technique with results comparable to that of IMRT plans. This technique can be proposed as a valid alternative when IMRT equipment is not available or patient is not suitable for IMRT treatment.

  1. Comparative study of four advanced 3d-conformal radiation therapy treatment planning techniques for head and neck cancer

    PubMed Central

    Herrassi, Mohamed Yassine; Bentayeb, Farida; Malisan, Maria Rosa

    2013-01-01

    For the head-and-neck cancer bilateral irradiation, intensity-modulated radiation therapy (IMRT) is the most reported technique as it enables both target dose coverage and organ-at-risk (OAR) sparing. However, during the last 20 years, three-dimensional conformal radiotherapy (3DCRT) techniques have been introduced, which are tailored to improve the classic shrinking field technique, as regards both planning target volume (PTV) dose conformality and sparing of OAR’s, such as parotid glands and spinal cord. In this study, we tested experimentally in a sample of 13 patients, four of these advanced 3DCRT techniques, all using photon beams only and a unique isocentre, namely Bellinzona, Forward-Planned Multisegments (FPMS), ConPas, and field-in-field (FIF) techniques. Statistical analysis of the main dosimetric parameters of PTV and OAR’s DVH’s as well as of homogeneity and conformity indexes was carried out in order to compare the performance of each technique. The results show that the PTV dose coverage is adequate for all the techniques, with the FPMS techniques providing the highest value for D95%; on the other hand, the best sparing of parotid glands is achieved using the FIF and ConPas techniques, with a mean dose of 26 Gy to parotid glands for a PTV prescription dose of 54 Gy. After taking into account both PTV coverage and parotid sparing, the best global performance was achieved by the FIF technique with results comparable to that of IMRT plans. This technique can be proposed as a valid alternative when IMRT equipment is not available or patient is not suitable for IMRT treatment. PMID:23776314

  2. Usefulness of Photodynamic Diagnosis and Therapy using Talaporfin Sodium for an Advanced-aged Patient with Inoperable Gastric Cancer (a secondary publication)

    PubMed Central

    Oinuma, Takeshi

    2014-01-01

    Background and aims: In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of elderly people being treated for cancer is increasing concomitantly. However, with the increase in age, the numbers of prior complications also increase. This is especially so in the advanced-aged patients, defined in Japan as those over the age of 85. Such complications may be too high risk for radical surgery and a less invasive treatment is warranted. Photodynamic therapy (PDT) is a noninvasive treatment approved by the Japanese National Health Insurance for the treatment of early stage superficial type esophageal and gastric cancers, early stage uterine cervical cancers and dysplasia, and early and advanced lung cancer. We report herein on the efficacy of palliative PDT using talaporfin sodium (Laserphyrin®) for a case of inoperable gastric cancer. Material and methods: The patient was an 87-year-old-man, a diabetic with histories of diabetic nephropathy, cerebral infarction and myocardial infarction. This patient was first diagnosed as having gastric cancer in 2007 but surgery and chemotherapy were contraindicated due to his poor physical status and poor renal function, respectively, owing to the anticipated side effects. The patient was referred to our institution after hearing of PDT in 2009. He was treated with 1 course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with photodynamic diagnosis (PDD) during the period from September, 2009 to June, 2011. Results: The massive gastric cancer located in the cardia was successfully treated with 4 PDT sessions without any serious complications; therefore the patient was able to orally ingest food until his death due to natural causes other than the cancer, in October, 2011. Conclusion: Talaporfin sodium PDT is safe and effective treatment for advanced-aged patients suffering from inoperable gastric cancer. PMID

  3. Recent advances in the treatment of colon cancer.

    PubMed

    Xu, R; Zhou, B; Fung, P C W; Li, X

    2006-08-01

    Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Although surgical resection is still the only treatment capable of curing colon cancer, adjuvant therapy continues to play an important role in preventing recurrence and metastasis. In recent years remarkable progress has been made in the treatment of colon cancer. This review discusses recent advances in adjuvant therapy for colon cancer, including chemotherapy, immunotherapy, antiangiogenic therapy and apoptosis induction. In the meantime, molecular therapy is also elucidated in the above methods. All these new advances will provide new promises for patients of colon cancer. PMID:16691539

  4. Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer.

    PubMed

    Chang, Joe Y; Jabbour, Salma K; De Ruysscher, Dirk; Schild, Steven E; Simone, Charles B; Rengan, Ramesh; Feigenberg, Steven; Khan, Atif J; Choi, Noah C; Bradley, Jeffrey D; Zhu, Xiaorong R; Lomax, Antony J; Hoppe, Bradford S

    2016-05-01

    Radiation dose escalation has been shown to improve local control and survival in patients with non-small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty because of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography-based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions. PMID:27084663

  5. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

    PubMed

    Rooney, Claire; Sethi, Tariq

    2015-10-01

    Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

  6. Radiation Therapy for Skin Cancer

    MedlinePlus

    ... Laser surgery Cancer cells are killed by laser beams.  Electrodessication The cancer is dried with an electric ... a chemical reaction that kills nearby cells. EXTERNAL BEAM RADIATION THERAPY External beam radiation therapy may be ...

  7. Accelerators for Cancer Therapy

    DOE R&D Accomplishments Database

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  8. High-dose paclitaxel with granulocyte colony-stimulating factor in patients with advanced breast cancer refractory to anthracycline therapy: a European Cancer Center trial.

    PubMed

    Vermorken, J B; ten Bokkel Huinink, W W; Mandjes, I A; Postma, T J; Huizing, M T; Heimans, J J; Beijnen, J H; Bierhorst, F; Winograd, B; Pinedo, H M

    1995-08-01

    Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a novel cytostatic agent that has shown interesting antitumor activity in patients with advanced breast cancer. Depending on variable patient characteristics and amount and type of prior therapy, as well as the applied dose and schedule of paclitaxel, response rates have varied from 13% to 62%. However, optimal dose and schedule are still unknown. We studied a high-dose (250 to 300 mg/m2) 3-hour paclitaxel infusion schedule in a poor prognostic group of breast cancer patients who progressed or relapsed while taking anthracyclines. This regimen was given every 3 weeks. Twenty-one of the 36 patients studied had increased liver enzymes and 18 had documented liver metastases. The objective response rate was only 6%, but response rate by disease site indicated that soft tissue lesions responded in 30% of cases. For a better comparison with other reported data a uniform definition of "anthracycline refractory" is needed. Neuropathy, which was found to be dose limiting, and arthralgia/myalgia syndrome were the most frequently occurring toxicities. Both severe myelosuppression (and infections) and severe diarrhea and mucositis were reported more frequently in patients with liver dysfunction. As higher peak levels, increased areas under the concentration time curves, and longer times during which plasma concentrations were above the threshold level of 0.1 mumol/L were found in patients with elevated liver enzymes, a correlation with the observed toxicities is assumed. Further pharmacodynamic studies in such patients receiving a 3-hour infusion seem warranted.

  9. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  10. Holistic cancer therapy.

    PubMed

    Magarey, C

    1983-01-01

    Medical technology has not reduced the death rate from cancer for 50 yrs, in spite of its physical and psychological morbidity. A broader approach is required and investigation of certain apparently successful unorthodox holistic cancer therapies suggests that the personality of the therapist is crucial. The spiritually convinced, charismatic healer has all the qualities of a meditator, and physiological measurement demonstrates that such a healer induces the state of meditation in his patients. Meditation is associated not only with physiological rest and stability, but also with the reduction of psychological stress and the development of a more positive attitude to life with an inner sense of calmness, strength and fulfilment. Holistic cancer therapy should include meditation, especially by the therapist; and psychosomatic research, like physics, should include the study of consciousness.

  11. Targeted polymeric nanoparticles for cancer gene therapy

    PubMed Central

    Kim, Jayoung; Wilson, David R.; Zamboni, Camila G.; Green, Jordan J.

    2015-01-01

    In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented. PMID:26061296

  12. Targeted polymeric nanoparticles for cancer gene therapy.

    PubMed

    Kim, Jayoung; Wilson, David R; Zamboni, Camila G; Green, Jordan J

    2015-01-01

    In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented.

  13. Multimodality Therapy: Bone-Targeted Radioisotope Therapy of Prostate Cancer

    PubMed Central

    Tu, Shi-Ming; Lin, Sue-Hwa; Podoloff, Donald A.; Logothetis, Christopher J.

    2016-01-01

    Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy. PMID:20551894

  14. Updates in Therapy for Advanced Melanoma.

    PubMed

    Singh, Bhavana P; Salama, April K S

    2016-01-15

    Cutaneous melanoma is one of the most aggressive forms of skin cancer, and is correlated with a large proportion of skin cancer-related deaths. Therapy for cutaneous melanoma has advanced greatly through careful identification of therapeutic targets and the development of novel immunotherapeutic approaches. The identification of BRAF as well as other driver mutations, have allowed for a specialized approach to treatment. In addition, immune checkpoint inhibition has dramatically changed the treatment landscape over the past 5-10 years. The successful targeting of CTLA-4, as well as PD-1/PD-L1, has been translated into meaningful clinical benefit for patients, with multiple other potential agents in development. Systemic therapy for cutaneous melanoma is becoming more nuanced and often takes a multifaceted strategy. This review aims to discuss the benefits and limitations of current therapies in systemic melanoma treatment as well as areas of future development.

  15. Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo- or targeted therapy

    PubMed Central

    Berardi, Rossana; Rinaldi, Silvia; Santoni, Matteo; Newsom-Davis, Thomas; Tiberi, Michela; Morgese, Francesca; Caramanti, Miriam; Savini, Agnese; Ferrini, Consuelo; Torniai, Mariangela; Fiordoliva, Ilaria; Bower, Marc; Cascinu, Stefano

    2016-01-01

    Background We aimed to assess the prognostic role of neutrophilia, lymphocytopenia and the neutrophil-to-lymphocyte ratio (NLR), and to design models to define the prognosis of patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). Materials and Methods We retrospectively analysed 401 consecutive patients with advanced NSCLC treated with first line chemo- or targeted therapy. Patients were stratified into two groups with pre-treatment NLR ≥ 3.7 (Group A) vs. < 3.7 (Group B). The best NLR cut-off was identified by ROC curve analysis. Results At baseline 264 patients had NLR≥3.7 (Group A), whilst 137 had lower NLR (Group B). Median OS was 10.8 months and 19.4 months in the two groups (p < 0.001), while median PFS was 3.6 months and 5.6 months, respectively (p = 0.012). At multivariate analysis, ECOG-PS≥2, stage IV cancer, non-adenocarcinoma histology, EGFR wild-type status and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR status and NLR≥3.7 were independent prognostic factors for worse PFS. Patients were stratified according to the presence of 0-1 prognostic factors (8%), 2-3 factors (73%) and 4-5 factors (19%) and median OS in these groups was 33.7 months, 14.6 months and 6.6 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0-1 prognostic factor (15%), 2 factors (41%) and 3 factors (44%). The median PFS was 8.3 months, 4.6 months and 3.3 months respectively (p < 0.001). Conclusion Pre-treatment NLR is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies. PMID:27029035

  16. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

    SciTech Connect

    Yeo, Seung-Gu; Oh, Jae Hwan; Kim, Dae Yong; Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun; Lee, Jong Hoon; Jang, Hong Seok; Kim, Jun-Gi; Lee, Myung Ah; Nam, Taek-Keun

    2013-05-01

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

  17. Building immunity to cancer with radiation therapy.

    PubMed

    Haikerwal, Suresh J; Hagekyriakou, Jim; MacManus, Michael; Martin, Olga A; Haynes, Nicole M

    2015-11-28

    Over the last decade there has been a dramatic shift in the focus of cancer research toward understanding how the body's immune defenses can be harnessed to promote the effectiveness of cytotoxic anti-cancer therapies. The ability of ionizing radiation to elicit anti-cancer immune responses capable of controlling tumor growth has led to the emergence of promising combination-based radio-immunotherapeutic strategies for the treatment of cancer. Herein we review the immunoadjuvant properties of localized radiation therapy and discuss how technological advances in radio-oncology and developments in the field of tumor-immunotherapy have started to revolutionize the therapeutic application of radiotherapy.

  18. Indirect comparison of the efficacy and safety of gefitinib and cetuximab-based therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    TANG, JIFENG; ZHANG, HENA; YAN, JIANZHOU; SHAO, RONG

    2015-01-01

    The aim of this study was to systematically evaluate the efficacy and safety of gefitinib and cetuximab-based therapies in patients with advanced non-small-cell lung cancer (NSCLC). The studies to be used for the comparisons were selected from the available literature on gefitinib and cetuximab-based therapies compared to conventional chemotherapy in patients with advanced NSCLC. The meta-analysis was performed with RevMan 5.0 software and the Bucher approach was applied to conduct the indirect comparisons. A total of 4 studies, including 935 patients, on gefitinib therapy vs. conventional chemotherapy and 4 studies, including 1,015 patients, on cetuximab-based therapy vs. conventional chemotherapy, were used for indirect comparisons. As regards efficacy, the risk ratio (RR) of objective response rate and 1-year survival rate between gefitinib and cetuximab-based therapies in patients with advanced NSCLC were 0.99 [95% confidence interval (CI): 0.75–1.32; P=0.9584] and 0.85 (95% CI: 0.71–1.01; P=0.0696), respectively, and the mean difference of progression-free survival and overall survival (OS) were −0.15 (95% CI: −0.90 to 0.60; P=0.6946) and −1.84 (95% CI: −3.53 to −0.15; P=0.0331), respectively. As regards safety, the RR of grade 3/4 adverse events (AEs) was 0.29 (95% CI: 0.19–0.44; P=0.0001). The results demonstrated that cetuximab-based therapy was superior to gefitinib therapy in terms of OS and inferior to gefitinib therapy in terms of AEs, whereas there were no significant differences in terms of efficacy and safety between the two therapies on other endpoints adopted for advanced NSCLC. However, further well-designed randomized controlled trials and continuous studies are required to confirm our findings. PMID:25469285

  19. STAT3 polymorphisms may predict an unfavorable response to first-line platinum-based therapy for women with advanced serous epithelial ovarian cancer.

    PubMed

    Permuth-Wey, Jennifer; Fulp, William J; Reid, Brett M; Chen, Zhihua; Georgeades, Christina; Cheng, Jin Q; Magliocco, Anthony; Chen, Dung-Tsa; Lancaster, Johnathan M

    2016-02-01

    Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC-related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case-control design was used to study 361 women with advanced-stage serous EOC treated with surgery followed by first-line platinum-based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. "Cases" included 102 incomplete responders (IRs) and "controls" included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC-related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP-level associations with an IR to therapy were identified for correlated (r(2) > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32-3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML = 0.006). rs1053004, a STAT3 SNP in a putative miRNA-binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors. PMID:26264211

  20. Cancer Therapy with Antiprotons

    SciTech Connect

    Bassler, Niels; Holzscheiter, Michael H.; Knudsen, Helge

    2005-10-26

    Starting in 2003 the AD-4/ACE collaboration has studied the biological effects of antiprotons annihilating in a human tissue like material on live V-79 Chinese Hamster cells. The main goal of the work is to prove the efficacy of antiprotons for cancer therapy. In this report we discuss a critical point to be considered carefully for all particle beam radiation therapies, namely the loss of primary particles from the beam on the way to a tumor seated some distance below the surface.

  1. TARGETED THERAPIES FOR PANCREATIC CANCER

    PubMed Central

    Danovi, S A; Wong, H H; Lemoine, N R

    2010-01-01

    Introduction Pancreatic cancer is a devastating malignancy and a leading cause of cancer mortality. Furthermore, early diagnosis represents a serious hurdle for clinicians as symptoms are non-specific and usually manifest in advanced, treatment-resistant stages of the disease. Sources of data Here, we review the rationale and progress of targeted therapies currently under investigation. Areas of agreement At present, chemoradiation regimes are administered palliatively, and produce only marginal survival benefits, underscoring a desperate need for more effective treatment modalities. Areas of controversy Questions have been raised as to whether erlotinib, the only targeted therapy to attain a statistically significant increase in median survival, is cost-effective. Growing points The last decade of research has provided us with a wealth of information regarding the molecular nature of pancreatic cancer, leading to the identification of signalling pathways and their respective components which are critical for the maintenance of the malignant phenotype. Areas timely for developing research These proteins thus represent ideal targets for novel molecular therapies which embody an urgently needed novel treatment strategy. PMID:18753179

  2. Evolution of the concept of focal therapy for prostate cancer.

    PubMed

    Tsivian, Matvey; Abern, Michael R; Polascik, Thomas J

    2013-01-01

    The landscape of prostate cancer has been rapidly evolving, and technological advances in imaging and biopsy tools offer novel approaches to focal therapy. In this dynamic environment, the role of focal therapy for prostate cancer is being shaped both by advances in technology and by reconsidering the epidemiological and outcomes data for available treatments. Here we focus on the evolution of the concept of focal therapy and its potential roles in the management of prostate cancer.

  3. Targeted therapies in gastroesophageal cancer.

    PubMed

    Kasper, Stefan; Schuler, Martin

    2014-05-01

    Gastroesophageal cancers comprising gastric cancer (GC), and cancers of the distal oesophagus and gastroesophageal junction (GEJ) are a global health threat. In Western populations the incidence of GC is declining which has been attributed to effective strategies of eradicating Helicobacter pylori infection. To the contrary, GEJ cancers are on the rise, with obesity and reflux disease being viewed as major risk factors. During the past decade perioperative chemotherapy, pre- or postoperative radio-chemotherapy, and, in Asian populations, adjuvant chemotherapy have been shown to improve the outcome of patients with advanced GC and GEJ cancers suited for surgery. Less progress has been made in the treatment of metastatic disease. The introduction of trastuzumab in combination with platinum/fluoropyrimidine-based chemotherapy for patients with HER2-positive disease has marked a turning point. Recently, several novel agents targeting growth factor receptors, angiogenic pathways, adhesion molecules and mediators of intracellular signal transduction have been clinically explored. Here we summarise the current status and future developments of molecularly targeted therapies in GC and GEJ cancer.

  4. Boron neutron capture therapy: Moving toward targeted cancer therapy.

    PubMed

    Mirzaei, Hamid Reza; Sahebkar, Amirhossein; Salehi, Rasoul; Nahand, Javid Sadri; Karimi, Ehsan; Jaafari, Mahmoud Reza; Mirzaei, Hamed

    2016-01-01

    Boron neutron capture therapy (BNCT) occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer. PMID:27461603

  5. Boron neutron capture therapy: Moving toward targeted cancer therapy.

    PubMed

    Mirzaei, Hamid Reza; Sahebkar, Amirhossein; Salehi, Rasoul; Nahand, Javid Sadri; Karimi, Ehsan; Jaafari, Mahmoud Reza; Mirzaei, Hamed

    2016-01-01

    Boron neutron capture therapy (BNCT) occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

  6. PET/CT Dose Planning for Volumetric Modulated Arc Radiation Therapy (VMAT) -Comparison with Conventional Approach in Advanced Prostate Cancer Patients.

    PubMed

    Kairemo, Kalevi; Rasulova, Nigora; Kiljunen, Timo; Partanen, Kaarina; Kangasmäki, Aki; Joensuu, Timo

    2015-01-01

    Molecular imaging is the only way of defining biological target volume (BTV) for externalbeam radiation therapy (EBRT) and may be used for advanced targeting in dose planning and dose painting. There are, however, no reports about the EBRT response when dose planning is based on BTV target definition in advanced prostate cancer. Clinical and biochemical results of two clinically equal group of patients with advanced prostate cancer patients were compared. Both groups were treated with volumetric modulated arc therapy (VMAT) based on target definition by PET/CT (1(st) group) or conventional imaging (2(nd) group). Biochemical relapse occurred in 16.6% (in 1 out of 6) of the patients in the first group and 50% (3 out of 6) patients in the second group during the follow up period. Clinical manifestation of disease occurred in 33% (2 out of 6) patients of the first group and in 5 out of 6 (83,3%) patients in the second one. 4 patients in the first group had no biochemical relapse and no clinical manifestation during the follow up period. The difference in the duration of progression free period was statistically significant between the groups (p<0.010) being in the first group 16.5±5.4 (10-24) months and 4.6±2.9 (2-10) months in the second one. Because patients with PET/CT based VMAT had lower incidence of biochemical relapse, less clinical manifestations and longer, statistically significant duration of progression free period as compared to patients treated with VMAT based on conventional imaging, our preliminary results suggest introducing BTV definition based on PET imaging for VMAT in the EBRT of prostate cancer.

  7. [A case of advanced esophageal cancer with liver metastases: efficacy of combination therapy of docetaxel/cisplatin/5-FU].

    PubMed

    Ehara, Kazuhisa; Tsutsumi, Kenji; Kinoshita, Yoshihiro; Ueno, Masaki; Mine, Shinji; Udagawa, Harushi

    2008-08-01

    The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is

  8. Targeting tumor suppressor genes for cancer therapy.

    PubMed

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.

  9. Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-PP) for Patients With Advanced Cancer.

    ClinicalTrials.gov

    2010-08-02

    Ovarian; Melanoma; Renal; Prostate; Colorectal; Endometrial Carcinoma; Cervical Carcinoma; Testicular Cancer; Thyroid Cancer; Small Cell Lung Carcinoma; Mesothelioma; Breast Carcinoma; Esophageal Carcinoma; Gastric Cancer; Pancreatic Carcinoma; Neuroendocrine Cancer; Liver Cancer; Gallbladder Cancer; Biliary Tract Cancer; Anal Carcinoma; Bone Sarcomas; Soft Tissue Sarcomas; Carcinoma of Unknown Origin, Primary

  10. [Radiation therapy of pancreatic cancer].

    PubMed

    Huguet, F; Mornex, F; Orthuon, A

    2016-09-01

    Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended. PMID:27523418

  11. [Radiation therapy of pancreatic cancer].

    PubMed

    Huguet, F; Mornex, F; Orthuon, A

    2016-09-01

    Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended.

  12. Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

    PubMed Central

    2016-01-01

    Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response. PMID:27672421

  13. Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

    PubMed Central

    2016-01-01

    Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response.

  14. Second- and Further-Line Therapy with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer in Daily Clinical Practice

    PubMed Central

    Krainhöfer, Josephine; Steinert, Matthias; Reissig, Angelika

    2014-01-01

    Introduction. The aim of this retrospective study was to examine effect of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) in second-line and further therapy in daily clinical practice. Methods. Patients with histologically or cytologically proven NSCLC (n = 84) treated with erlotinib in second-line (n = 34), third-line (n = 36), and more-line therapy (n = 14) were examined for progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of therapy, and adverse effects. Results. Median PFS of all lines was 83 days (CI 70.0–96.0), OS was 7 months (CI 4.7–9.3), DCR was 66.2% (CI 55–77%), and 1-year survival rate was 33% (CI 22–43%), with no significant difference between therapy lines. Median duration of treatment was 76 days (IQR 39–139.5). Patients with epidermal growth factor receptor mutation (EGFR-M) reached the highest PFS (204 days), as did patients with good performance status (ECOG 0-1: 94 versus ECOG 2-3: 65 days, P = 0.035). Patients with EGFR-M also revealed a DCR of 100%. The most frequent side effects were rash (69%) and diarrhoea (41%), without any significant difference between therapy lines. In 24 patients, the treatment dose was reduced and in 18, the therapy was paused. Conclusion. Erlotinib works in all therapy lines without any significant differences in efficacy and side effects. PMID:25028671

  15. New developments in metastatic prostate cancer therapy.

    PubMed

    Manickavasagar, Thubeena; Gilson, Clare; Chowdhury, Simon; Kirby, Roger

    2015-04-01

    Metastatic prostate cancer is still commonly a lethal condition. The concept that 'men with prostate cancer die with rather than of their cancer' has been shown to be false. It is estimated that 10-20% of men in the UK present with locally advanced disease. Median overall survival remains only 3.5 years for men presenting with metastatic disease. The use of LHRH analogues to achieve medical castration has become the gold standard for both locally advanced prostate cancer, combined with radiotherapy, and metastatic disease. Androgen deprivation therapy (ADT) is the standard first-line treatment for advanced disease resulting in improvements in symptoms, radiological findings and PSA levels. Ultimately the majority of men with advanced prostate cancer will develop resistance to ADT Docetaxel is the standard first-line therapy recommended by international guidelines for patients with symptomatic metastatic castrate refractory prostate cancer who are suitable candidates for chemotherapy. More than 90% of patients with castrate refractory prostate cancer have bone metastases. Radium-223 dichloride is a novel alpha-emitting radiopharmaceutical agent, which mimics calcium and therefore targets bone metastases. It is indicated in patients with metastatic castrate refractory prostate cancer who have symptomatic bone metastases without visceral metastases.

  16. Advances in radiation therapy dosimetry

    PubMed Central

    Paliwal, Bhudatt; Tewatia, Dinesh

    2009-01-01

    During the last decade, there has been an explosion of new radiation therapy planning and delivery tools. We went through a rapid transition from conventional three-dimensional (3D) conformal radiation therapy to intensity-modulated radiation therapy (IMRT) treatments, and additional new techniques for motion-adaptive radiation therapy are being introduced. These advances push the frontiers in our effort to provide better patient care; and with the addition of IMRT, temporal dimensions are major challenges for the radiotherapy patient dosimetry and delivery verification. Advanced techniques are less tolerant to poor implementation than are standard techniques. Mis-administrations are more difficult to detect and can possibly lead to poor outcomes for some patients. Instead of presenting a manual on quality assurance for radiation therapy, this manuscript provides an overview of dosimetry verification tools and a focused discussion on breath holding, respiratory gating and the applications of four-dimensional computed tomography in motion management. Some of the major challenges in the above areas are discussed. PMID:20098555

  17. Radiation Therapy for Testicular Cancer

    MedlinePlus

    ... therapy for testicular cancer Radiation therapy uses a beam of high-energy rays (such as gamma rays ... machine outside the body is known as external beam radiation . The treatment is much like getting an ...

  18. DNA Repair and Personalized Breast Cancer Therapy

    PubMed Central

    Li, Shu-Xia; Sjolund, Ashley; Harris, Lyndsay; Sweasy, Joann B.

    2010-01-01

    Personalized cancer therapy is likely to be one of the next big advances in our search for a cure for cancer. To be able to treat people in an individualized manner, researchers need to know a great deal about their genetic constitution and the DNA repair status of their tumors. Specific knowledge is required regarding the polymorphisms individuals carry and how these polymorphisms influence responses to therapy. Researchers are actively engaged in biomarker discovery and validation for this purpose. In addition, the design of clinical trials must be reassessed to include new information on biomarkers and drug responses. In this review, we focus on personalized breast cancer therapy. The hypothesis we focus upon in this review is that there is connection between the DNA repair profile of individuals, their breast tumor subtypes, and their responses to cancer therapy. We first briefly review cellular DNA repair pathways that are likely to be impacted by breast cancer therapies. Next, we review the phenotypes of breast tumor subtypes with an emphasis on how a DNA repair deficiency might result in tumorigenesis itself and lead to the chemotherapeutic responses that are observed. Specific examples of breast tumor subtypes and their responses to cancer therapy are given, and we discuss possible DNA repair mechanisms that underlie the responses of tumors to various chemotherapeutic agents. Much is known about breast cancer subtypes and the way each of these subtypes responds to chemotherapy. In addition, we discuss novel design of clinical trials that incorporates rapidly emerging information on biomarkers. PMID:20872853

  19. Photodynamic Therapy for Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  20. Biological Therapies for Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  1. Particle therapy for cancers: a new weapon in radiation therapy.

    PubMed

    Jiang, Guo-Liang

    2012-06-01

    Particle irradiation started to draw attention in the past decade and has now become a hotspot in the radiation oncology community. This article reviews the most advanced developments in particle irradiation, focusing on the characteristics of proton and carbon ions in radiation physics and radiobiology. The Bragg peak of physical dose distribution causes proton and carbon beams to optimally meet the requirement for cancer irradiation because the Bragg peak permits the accurate concentration of the dose on the tumor, thus sparing the adjacent normal tissues. Moreover, carbon ion has more radiobiological benefits than photon and proton beams. These benefits include stronger sterilization effects on intrinsic radio-resistant tumors and more effective killing of hypoxic, G(0), and S phase cells. Compared with the most advanced radiation techniques using photon, such as three-dimensional conformal radiation therapy and intensity-modulated radiation therapy, proton therapy has yielded more promising outcomes in local control and survival for head and neck cancers, prostate carcinoma, and pediatric cancers. Carbon therapy in Japan showed even more promising results than proton therapy. The local controls and overall survivals were as good as that treated by surgery in early stages of non-small cell lung cancer, hepatocellular carcinoma, prostate carcinoma, and head and neck cancers, especially for such highly resistant tumors as melanoma. The non-invasive nature of particle therapy affords more patients with chances to receive and benefit from treatment. Particle therapy is gradually getting attention from the oncology community. However, the cost of particle therapy facilities has limited the worldwide use of this technology.

  2. The Efficacy of Chinese Herbal Medicine as an Adjunctive Therapy for Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis

    PubMed Central

    Ou-Yang, Chen Sheng; Wang, Xi-Xin; Yang, Zhen-Jiang; Tong, Yao; Cho, William C.S.

    2013-01-01

    Many published studies reflect the growing application of complementary and alternative medicine, particularly Chinese herbal medicine (CHM) use in combination with conventional cancer therapy for advanced non-small cell lung cancer (NSCLC), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with conventional chemotherapy (CT) in the treatment of advanced NSCLC. Publications in 11 electronic databases were extensively searched, and 24 trials were included for analysis. A sum of 2,109 patients was enrolled in these studies, at which 1,064 patients participated in CT combined CHM and 1,039 in CT (six patients dropped out and were not reported the group enrolled). Compared to using CT alone, CHM combined with CT significantly increase one-year survival rate (RR = 1.36, 95% CI = 1.15–1.60, p = 0.0003). Besides, the combined therapy significantly increased immediate tumor response (RR = 1.36, 95% CI = 1.19–1.56, p<1.0E−5) and improved Karnofsky performance score (KPS) (RR = 2.90, 95% CI = 1.62–5.18, p = 0.0003). Combined therapy remarkably reduced the nausea and vomiting at toxicity grade of III–IV (RR = 0.24, 95% CI = 0.12–0.50, p = 0.0001) and prevented the decline of hemoglobin and platelet in patients under CT at toxicity grade of I–IV (RR = 0.64, 95% CI = 0.51–0.80, p<0.0001). Moreover, the herbs that are frequently used in NSCLC patients were identified. This systematic review suggests that CHM as an adjuvant therapy can reduce CT toxicity, prolong survival rate, enhance immediate tumor response, and improve KPS in advanced NSCLC patients. However, due to the lack of large-scale randomized clinical trials in the included studies, further larger scale trials are needed. PMID:23469033

  3. Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography

    NASA Astrophysics Data System (ADS)

    Enfield, Louise; Cantanhede, Gabriel; Douek, Michael; Ramalingam, Vernie; Purushotham, Arnie; Hebden, Jem; Gibson, Adam

    2013-05-01

    Optical mammography is a functional imaging technique that uses near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and hemoglobin concentration. It has been used to monitor the response to neoadjuvant chemotherapy in breast cancer patients. We present the first results on monitoring tumor response to hormone therapy using optical mammography. We present three case studies from postmenopausal women treated with neoadjuvant hormone therapy for locally advanced breast cancer. The women were scanned before starting treatment, once during treatment, and then before surgery. Changes in physiological and optical properties within the tumor and in the rest of the breast were evaluated. At the time of surgery, two patients partially responded to treatment and one did not respond. The patients that partially responded on ultrasound revealed a corresponding recovery to normal in the hemoglobin concentration images, whereas the nonresponder indicated an increase in hemoglobin concentration in the tumor compared to her pretreatment images. These case studies suggest that optical imaging of the breast during neoadjuvant hormone treatment can provide potentially valuable information, and that physiological changes within the tumor can be seen in response to treatment.

  4. Targeted therapy in head and neck cancer.

    PubMed

    Ward, Brent B

    2013-02-01

    The desire to target therapies to specific cancers while leaving the host unharmed remains an ongoing quest for scientists, surgeons, radiation oncologists, and medical oncologists. In recent years, great scientific progress has been made in targeted therapies. Although many modalities remain in preclinical validation, some advances affect patient care today. This article summarizes the concepts of targeting and explores current examples of successful targeting and emerging targeting technologies in head and neck oncology. PMID:23399398

  5. Photodynamic therapy for cancer

    MedlinePlus

    ... Cancer of the esophagus-photodynamic; Esophageal cancer-photodynamic; Lung cancer-photodynamic ... the light at the cancer cells. PDT treats cancer in the: Lungs, using a bronchoscope Esophagus, using upper endoscopy Doctors ...

  6. [A 5-year survival case of locally advanced cancer of the pancreatic body treated by distal pancreatectomy with en bloc celiac axis resection after neoadjuvant chemoradiation therapy].

    PubMed

    Iseki, Masahiro; Motoi, Fuyuhiko; Mizuma, Masamichi; Hayashi, Hiroki; Nakagawa, Kei; Okada, Takaho; Otsuka, Hideo; Ottomo, Shigeru; Sakata, Naoaki; Fukase, Koji; Yoshida, Hiroshi; Onogawa, Tohru; Naito, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

    2012-11-01

    A 59-year-old man was diagnosed with locally advanced cancer of the pancreatic body, involving the nerve plexus around the celiac axis, the common hepatic artery, and the splenic artery. He was treated with a combination of irradiation (2 Gy/day, total 24 Gy) and 600 mg/m2 of gemcitabine(GEM)biweekly. The tumor size and the involved plexus area were not diminished, but CA19-9 was reduced by half. Distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histological findings indicated extensive invasion into the nerve plexus, including that adjacent to the stump of the pancreas, and thus the R classification was R1. After surgery, 1,000 mg/m2 of GEM was administered biweekly. The chemotherapy has been performed for 5 years to prevent local and systemic recurrence. No recurrence has been found 5 years after surgery. Multidisciplinary treatment, combined with neoadjuvant chemoradiation therapy, curative-intent resection, and postoperative chemotherapy is important for effective treatment of locally advanced pancreatic cancer. PMID:23267939

  7. Hadron Therapy for Cancer Treatment

    SciTech Connect

    Lennox, Arlene

    2003-09-10

    The biological and physical rationale for hadron therapy is well understood by the research community, but hadron therapy is not well established in mainstream medicine. This talk will describe the biological advantage of neutron therapy and the dose distribution advantage of proton therapy, followed by a discussion of the challenges to be met before hadron therapy can play a significant role in treating cancer. A proposal for a new research-oriented hadron clinic will be presented.

  8. Single-Fraction Stereotactic Body Radiation Therapy and Sequential Gemcitabine for the Treatment of Locally Advanced Pancreatic Cancer

    SciTech Connect

    Schellenberg, Devin; Kim, Jeff; Christman-Skieller, Claudia; Chun, Carlene L.; Columbo, Laurie Ann; Ford, James M.; Fisher, George A.; Kunz, Pamela L.; Van Dam, Jacques; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Hsu, Annie; Maxim, Peter G.; Xing, Lei; Goodman, Karyn A.; Chang, Daniel T.; Koong, Albert C.

    2011-09-01

    Purpose: This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT). Methods and Materials: Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year. Conclusion: Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

  9. Potential Benefits of Scanned Intensity-Modulated Proton Therapy Versus Advanced Photon Therapy With Regard to Sparing of the Salivary Glands in Oropharyngeal Cancer

    SciTech Connect

    Water, Tara A. van de; Bijl, Hendrik P.; Jong, Marije E. de; Schilstra, Cornelis; Langendijk, Johannes A.

    2011-03-15

    Purpose: To test the hypothesis that scanned intensity-modulated proton therapy (IMPT) results in a significant dose reduction to the parotid and submandibular glands as compared with intensity-modulated radiotherapy with photons (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for oropharyngeal cancer. In addition, we investigated whether the achieved dose reductions would theoretically translate into a reduction of salivary dysfunction and xerostomia. Methods and Materials: Ten patients with N0 oropharyngeal carcinoma were used. The intensity-modulated plans delivered simultaneously 70 Gy to the boost planning target volume (PTV2) and 54 Gy to the elective nodal areas (PTV1). The 3D-CRT technique delivered sequentially 70 Gy and 46 Gy to PTV2 and PTV1, respectively. Normal tissue complication probabilities were calculated for salivary dysfunction and xerostomia. Results: Planning target volume coverage results were similar for IMPT and IMRT. Intensity-modulated proton therapy clearly improved the conformity. The 3D-CRT results were inferior to these results. The mean dose to the parotid glands by 3D-CRT (50.8 Gy), IMRT (25.5 Gy), and IMPT (16.8 Gy) differed significantly. For the submandibular glands no significant differences between IMRT and IMPT were found. The dose reductions obtained with IMPT theoretically translated into a significant reduction in normal tissue complication probability. Conclusion: Compared with IMRT and 3D-CRT, IMPT improved sparing of the organs at risk, while keeping similar target coverage results. The dose reductions obtained with IMPT vs. IMRT and 3D-CRT varied widely per individual patient. Intensity-modulated proton therapy theoretically translated into a clinical benefit for most cases, but this requires clinical validation.

  10. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.

    PubMed

    Coronel, Jaime; Cetina, Lucely; Pacheco, Irlanda; Trejo-Becerril, Catalina; González-Fierro, Aurora; de la Cruz-Hernandez, Erick; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Arias-Bofill, Daymi; Candelaria, Myrna; Vidal, Silvia; Dueñas-González, Alfonso

    2011-12-01

    The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1-22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.

  11. Biofield therapies and cancer pain.

    PubMed

    Anderson, Joel G; Taylor, Ann Gill

    2012-02-01

    The public and healthcare professionals have become increasingly aware and accepting of the benefit in physical, psychological, social, and spiritual support for patients with cancer. Patients with cancer often seek nonpharmacologic interventions to complement conventional care and decrease the pain associated with cancer and its treatment. Most often referred to as complementary and alternative medicine (CAM), these supportive therapies consist of a heterogeneous group of modalities used as adjuncts to allopathic health care. Biofield therapies are CAM modalities that involve the direction of healing energy through the hands to facilitate well-being by modifying the energy field of the body. This critical review of studies of biofield therapies emphasizes research using these modalities to decrease pain in patients with cancer. Although the therapies have demonstrated clinical efficacy, additional research is warranted. Oncology nurses should familiarize themselves with biofield therapies so they can offer informed recommendations to patients with cancer experiencing pain.

  12. Type of Cancer Treatment: Targeted Therapy

    Cancer.gov

    Information about the role that targeted therapies play in cancer treatment. Includes how targeted therapies work against cancer, who receives targeted therapies, common side effects, and what to expect when having targeted therapies.

  13. The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

    SciTech Connect

    Doll, Corinne M.; Aquino-Parsons, Christina; Pintilie, Melania; Petrillo, Stephanie K.; Milosevic, Michael; Craighead, Peter S.; Clarke, Blaise; Lees-Miller, Susan P.; Fyles, Anthony W.; Magliocco, Anthony M.

    2013-03-01

    Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

  14. Gonadotropin-releasing hormone antagonists versus standard androgen suppression therapy for advanced prostate cancer A systematic review with meta-analysis

    PubMed Central

    Kunath, Frank; Borgmann, Hendrik; Blümle, Anette; Keck, Bastian; Wullich, Bernd; Schmucker, Christine; Sikic, Danijel; Roelle, Catharina; Schmidt, Stefanie; Wahba, Amr; Meerpohl, Joerg J

    2015-01-01

    Objectives To evaluate efficacy and safety of gonadotropin-releasing hormone (GnRH) antagonists compared to standard androgen suppression therapy for advanced prostate cancer. Setting The international review team included methodologists of the German Cochrane Centre and clinical experts. Participants We searched CENTRAL, MEDLINE, Web of Science, EMBASE, trial registries and conference books for randomised controlled trials (RCT) for effectiveness data analysis, and randomised or non-randomised controlled studies (non-RCT) for safety data analysis (March 2015). Two authors independently screened identified articles, extracted data, evaluated risk of bias and rated quality of evidence according to GRADE. Results 13 studies (10 RCTs, 3 non-RCTs) were included. No study reported cancer-specific survival or clinical progression. There were no differences in overall mortality (RR 1.35, 95% CI 0.63 to 2.93), treatment failure (RR 0.91, 95% CI 0.70 to 1.17) or prostate-specific antigen progression (RR 0.83, 95% CI 0.64 to 1.06). While there was no difference in quality of life related to urinary symptoms, improved quality of life regarding prostate symptoms, measured with the International Prostate Symptom Score (IPSS), with the use of GnRH antagonists compared with the use of standard androgen suppression therapy (mean score difference −0.40, 95% CI −0.94 to 0.14, and −1.84, 95% CI −3.00 to −0.69, respectively) was found. Quality of evidence for all assessed outcomes was rated low according to GRADE. The risk for injection-site events was increased, but cardiovascular events may occur less often by using GnRH antagonist. Available evidence is hampered by risk of bias, selective reporting and limited follow-up. Conclusions There is currently insufficient evidence to make firm conclusive statements on the efficacy of GnRH antagonist compared to standard androgen suppression therapy for advanced prostate cancer. There is need for further high-quality research on

  15. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    PubMed Central

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2012-01-01

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTVP) and involved lymph nodes (GTVLN) to simulate the localization process in image-guided radiation therapy. Techniques included “standard” (direct registration of weekly images to a planning CT), “seeded” (manual prealignment of targets to guide standard registration), “transitive-based” (alignment of pretreatment and planning CTs through one or more intermediate images), and “rereferenced” (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 ± 5.4 mm and 5.4 ± 3.4 mm for the GTVP and GTVLN, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTVP centroid LE to 4.7 ± 3.7 mm (p = 0.011) and 4.3 ± 2.5 mm (p < 1 × 10−3), respectively, but the smallest GTVP LE of 2.4 ± 2.1 mm was provided by rereferenced registration (p < 1 × 10−6). Standard registration significantly reduced GTVLN centroid LE to 3.2 ± 2.5 mm (p < 1 × 10−3) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low as 3

  16. Major clinical research advances in gynecologic cancer in 2015

    PubMed Central

    2016-01-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

  17. Personalized therapy for lung cancer.

    PubMed

    Moreira, Andre L; Eng, Juliana

    2014-12-01

    The past decade has seen an enormous advancement in the therapy for lung cancer, predominantly seen in adenocarcinoma, ranging from the introduction of histology-based drugs to the discovery of targetable mutations. These events have led to a personalized therapeutic approach with the delivery of drugs that target specific oncogenic pathways active in a given tumor with the intent of acquiring the best response rate. The discovery of sensitizing mutation in the epidermal growth factor receptor gene as the basis for clinical response to tyrosine kinase inhibitors led to a systematic search for other molecular targets in lung cancer. Currently, there are several molecular alterations that can be targeted by experimental drugs. These new discoveries would not be possible without a parallel technological evolution in diagnostic molecular pathology. Next-generation sequencing (NGS) is a technology that allows for the evaluation of multiple molecular alterations in the same sample using a small amount of tissue. Selective evaluation of targeted cancer genes, instead of whole-genome evaluation, is the approach that is best suited to enter clinical practice. This technology allows for the detection of most molecular alteration with a single test, thus saving tissue for future discoveries. The use of NGS is expected to increase and gain importance in clinical and experimental approaches, since it can be used as a diagnostic tool as well as for new discoveries. The technique may also help us elucidate the interplay of several genes and their alteration in the mechanism of drug response and resistance.

  18. Interfraction Displacement of Primary Tumor and Involved Lymph Nodes Relative to Anatomic Landmarks in Image Guided Radiation Therapy of Locally Advanced Lung Cancer

    SciTech Connect

    Jan, Nuzhat; Balik, Salim; Hugo, Geoffrey D.; Mukhopadhyay, Nitai; Weiss, Elisabeth

    2014-01-01

    Purpose: To analyze primary tumor (PT) and lymph node (LN) position changes relative to each other and relative to anatomic landmarks during conventionally fractionated radiation therapy for patients with locally advanced lung cancer. Methods and Materials: In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina, and 1 thoracic vertebra were manually contoured on weekly 4-dimensional fan-beam CT scans. Systematic and random interfraction displacements of all contoured structures were identified in the 3 cardinal directions, and resulting setup margins were calculated. Time trends and the effect of volume changes on displacements were analyzed. Results: Three-dimensional displacement vectors and systematic/random interfraction displacements were smaller for carina than for vertebra both for PT and LN. For PT, mean (SD) 3-dimensional displacement vectors with carina-based alignment were 7 (4) mm versus 9 (5) mm with bony anatomy (P<.0001). For LN, smaller displacements were found with carina- (5 [3] mm, P<.0001) and vertebra-based (6 [3] mm, P=.002) alignment compared with using PT for setup (8 [5] mm). Primary tumor and LN displacements relative to bone and carina were independent (P>.05). Displacements between PT and bone (P=.04) and between PT and LN (P=.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (P=.03). Conclusions: Carina-based setup results in a more reproducible PT and LN alignment than bony anatomy setup. Considering the independence of PT and LN displacement and the impact of volume regression on displacements over time, repeated CT imaging even with PT-based alignment is recommended in locally advanced disease.

  19. Vaccine therapy in non-small-cell lung cancer.

    PubMed

    Albright, Carol; Garst, Jennifer

    2007-07-01

    Lung cancer is the leading cause of death from cancer worldwide. First-line therapy is based on stage at diagnosis and can include chemotherapy, radiation, and surgery. Despite advances, the prognosis for advanced-stage lung cancer is very poor. Vaccines with the capability to activate the host immune system may have a role in second-line therapy. Advances in the understanding of cellular and molecular immunology are forming the basis for improving vaccine therapy. Most trials to date have demonstrated safety but inconsistent efficacy. Further research is needed to enhance this potential. PMID:17588347

  20. Advances in Radiotherapy Management of Esophageal Cancer

    PubMed Central

    Verma, Vivek; Moreno, Amy C.; Lin, Steven H.

    2016-01-01

    Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC. PMID:27775643

  1. Buffer Therapy for Cancer

    PubMed Central

    Ribeiro, Maria de Lourdes C; Silva, Ariosto S.; Bailey, Kate M.; Kumar, Nagi B.; Sellers, Thomas A.; Gatenby, Robert A.; Ibrahim-Hashim, Arig; Gillies, Robert J.

    2013-01-01

    Oral administration of pH buffers can reduce the development of spontaneous and experimental metastases in mice, and has been proposed in clinical trials. Effectiveness of buffer therapy is likely to be affected by diet, which could contribute or interfere with the therapeutic alkalinizing effect. Little data on food pH buffering capacity was available. This study evaluated the pH and buffering capacity of different foods to guide prospective trials and test the effect of the same buffer (lysine) at two different ionization states. Food groups were derived from the Harvard Food Frequency Questionnaire. Foods were blended and pH titrated with acid from initial pH values until 4.0 to determine “buffering score”, in mmol H+/pH unit. A “buffering score” was derived as the mEq H+ consumed per serving size to lower from initial to a pH 4.0, the postprandial pH of the distal duodenum. To differentiate buffering effect from any metabolic byproduct effects, we compared the effects of oral lysine buffers prepared at either pH 10.0 or 8.4, which contain 2 and 1 free base amines, respectively. The effect of these on experimental metastases formation in mice following tail vein injection of PC-3M prostate cancer cells were monitored with in vivo bioluminescence. Carbohydrates and dairy products’ buffering score varied between 0.5 and 19. Fruits and vegetables showed a low to zero buffering score. The score of meats varied between 6 and 22. Wine and juices had negative scores. Among supplements, sodium bicarbonate and Tums® had the highest buffering capacities, with scores of 11 and 20 per serving size, respectively. The “de-buffered” lysine had a less pronounced effect of prevention of metastases compared to lysine at pH 10. This study has demonstrated the anti-cancer effects of buffer therapy and suggests foods that can contribute to or compete with this approach to manage cancer. PMID:24371544

  2. A Phase II Clinical Study of mFOLFOX6 Plus Bevacizumab as First-line Therapy for Japanese Advanced/Recurrent Colorectal Cancer Patients

    PubMed Central

    Nishina, Tomohiro; Takano, Yoshinao; Denda, Tadamichi; Yasui, Hisateru; Takeda, Koji; Ura, Takashi; Esaki, Taito; Okuyama, Yusuke; Kondo, Ken; Takahashi, Yasuo; Sugiyama, Yasuyuki; Muro, Kei

    2013-01-01

    Objective In Japan, there had been no prospective clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy. We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer. Methods Bevacizumab (5 mg/kg) was administered intravenously, and then oxaliplatin (85 mg/m2) and levofolinate calcium (200 mg/m2) were infused intravenously over 2 h. Subsequently, a bolus dose of 5-fluorouracil (400 mg/m2) was injected, followed by infusion of 5-fluorouracil (2400 mg/m2) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression, unacceptable toxicity or patient refusal. The primary end point was the response rate. Results Among the 70 patients enrolled, two patients withdrew the study before treatment, and 68 patients were eligible for analysis of efficacy and safety. The response rate was 51.5% (95% confidence interval: 39.0–63.8%). The median progression-free survival and median overall survival time were 12.6 months (95% confidence interval: 10.4–14.5 months) and 28.5 months [95% confidence interval: 23.1 months–(not applicable)], respectively. There were no treatment-related deaths observed. The most common Grade 3 and 4 adverse events included neutropenia in 35.3% of the patients, peripheral neuropathy in 16.2% and hypertension in 16.2%. All adverse events were manageable and tolerable. The exploratory analysis of polymorphisms of three genes, ERCC1, XPD and GSTP1, did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy. Conclusions Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients, achieving a high response rate. PMID:23999770

  3. MRI for Assessing Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer Using DCE-MR and DW-MR Data Sets: A Preliminary Report.

    PubMed

    Petrillo, Mario; Fusco, Roberta; Catalano, Orlando; Sansone, Mario; Avallone, Antonio; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Petrillo, Antonella

    2015-01-01

    To evaluate MRI for neoadjuvant therapy response assessment in locally advanced rectal cancer (LARC) using dynamic contrast enhanced-MRI (DCE-MRI) and diffusion weighted imaging (DWI), we have compared magnetic resonance volumetry based on DCE-MRI (V(DCE)) and on DWI (V(DWI)) scans with conventional T2-weighted volumetry (V(C)) in LARC patients after neoadjuvant therapy. Twenty-nine patients with LARC underwent MR examination before and after neoadjuvant therapy. A manual segmentation was performed on DCE-MR postcontrast images, on DWI (b-value 800 s/mm(2)), and on conventional T2-weighted images by two radiologists. DCE-MRI, DWI, and T2-weigthed volumetric changes before and after treatment were evaluated. Nonparametric sample tests, interobserver agreement, and receiver operating characteristic curve (ROC) were performed. Diagnostic performance linked to DCE-MRI volumetric change was superior to T2-w and DW-MRI volumetric changes performance (specificity 86%, sensitivity 93%, and accuracy 93%). Area Under ROC (AUC) of V(DCE) was greater than AUCs of V(C) and V(DWI) resulting in an increase of 15.6% and 11.1%, respectively. Interobserver agreement between two radiologists was 0.977, 0.864, and 0.756 for V(C), V(DCE), and V(DWI), respectively. V(DCE) seems to be a promising tool for therapy response assessment in LARC. Further studies on large series of patients are needed to refine technique and evaluate its potential value. PMID:26413528

  4. MRI for Assessing Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer Using DCE-MR and DW-MR Data Sets: A Preliminary Report

    PubMed Central

    Petrillo, Mario; Fusco, Roberta; Catalano, Orlando; Sansone, Mario; Avallone, Antonio; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Petrillo, Antonella

    2015-01-01

    To evaluate MRI for neoadjuvant therapy response assessment in locally advanced rectal cancer (LARC) using dynamic contrast enhanced-MRI (DCE-MRI) and diffusion weighted imaging (DWI), we have compared magnetic resonance volumetry based on DCE-MRI (V(DCE)) and on DWI (V(DWI)) scans with conventional T2-weighted volumetry (V(C)) in LARC patients after neoadjuvant therapy. Twenty-nine patients with LARC underwent MR examination before and after neoadjuvant therapy. A manual segmentation was performed on DCE-MR postcontrast images, on DWI (b-value 800 s/mm2), and on conventional T2-weighted images by two radiologists. DCE-MRI, DWI, and T2-weigthed volumetric changes before and after treatment were evaluated. Nonparametric sample tests, interobserver agreement, and receiver operating characteristic curve (ROC) were performed. Diagnostic performance linked to DCE-MRI volumetric change was superior to T2-w and DW-MRI volumetric changes performance (specificity 86%, sensitivity 93%, and accuracy 93%). Area Under ROC (AUC) of V(DCE) was greater than AUCs of V(C) and V(DWI) resulting in an increase of 15.6% and 11.1%, respectively. Interobserver agreement between two radiologists was 0.977, 0.864, and 0.756 for V(C), V(DCE), and V(DWI), respectively. V(DCE) seems to be a promising tool for therapy response assessment in LARC. Further studies on large series of patients are needed to refine technique and evaluate its potential value. PMID:26413528

  5. Impact of Pretreatment Combined {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging on Radiation Therapy Treatment Decisions in Locally Advanced Breast Cancer

    SciTech Connect

    Ng, Sweet Ping; David, Steven; Alamgeer, Muhammad; Ganju, Vinod

    2015-09-01

    Purpose: To assess the diagnostic performance of pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). Methods and Materials: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body {sup 18}F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. Results: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. Conclusions: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary

  6. A dosimetric evaluation of dose escalation for the radical treatment of locally advanced vulvar cancer by intensity-modulated radiation therapy

    SciTech Connect

    Bloemers, Monique C.W.M.; Portelance, Lorraine; Ruo, Russell; Parker, William; Souhami, Luis

    2012-10-01

    The purpose of this planning study was to determine whether intensity-modulated radiation therapy (IMRT) reduces the radiation dose to organs at risk (OAR) when compared with 3D conventional radiation therapy (3D-CRT) in patients with vulvar cancer treated by irradiation. This study also investigated the use of sequential IMRT boost (seq-IMRT) and simultaneous integrated boost (SIB-IMRT) for dose escalation in the treatment of locally advanced vulvar cancer. Five vulvar cancer patients treated in the postoperative setting and 5 patients treated with definitive intent (def-group) were evaluated. For the postoperative group, 3D-CRT and IMRT plans to a total dose (TD) of 45 Gy were generated. For the def-group, 4 plans were generated: a 3D-CRT and an IMRT plan to a TD of 56.4 Gy, a SIB-IMRT plan to a TD of 56 Gy, and a SIB-IMRT with dose escalation (SIB-IMRT-esc): TD of 67.2 Gy. Mean dose and dose-volume histograms were compared using Student's t-test. IMRT significantly (all p < 0.05) reduced the D{sub mean}, V30, and V40 for all OAR in the adjuvant setting. The V45 was also significantly reduced for all OAR except the bladder. For patients treated in the def-group, all IMRT techniques significantly reduced the D{sub mean}, V40, and V45 for all OAR. The mean femur doses with SIB-IMRT and SIB-IMRT-esc were 47% and 49% lower compared with 3D-CRT. SIB-IMRT-esc reduced the doses to the OAR compared with seq-3D-CRT but increased the D{sub max.} for the small bowel, rectum, and bladder. IMRT reduces the dose to the OAR compared with 3D-CRT in patients with vulvar cancer receiving irradiation to a volume covering the vulvar region and nodal areas without compromising the dosimetric coverage of the target volume. IMRT for vulvar cancer is feasible and an attractive option for dose escalation studies.

  7. Treating cancer with infection: a review on bacterial cancer therapy.

    PubMed

    Wong, S; Slavcev, R A

    2015-08-01

    There is an increasing need for new cancer therapies. The antitumour effect of bacterial infection has been well observed and practiced throughout history. Bacteria are well-suited to serve as anticancer agents due to their intrinsic mobility, cell toxicity, immunogenicity, and preferential accumulation within the anoxic tumour environment. Furthermore, advances in biotechnology and molecular techniques have made it easier than ever to engineer bacteria as both therapeutic agents themselves and as therapeutic vectors. Here, we review bacteriolytic therapy and immunotherapy strategies, and examine the development of bacteria as vehicles for cell- and tissue-targeted delivery of genetic cancer therapeutics.

  8. [Combination therapy of continuous venous infusion (CVI) of 5-FU and low dose consecutive cisplatin (CDDP), and the new oral anti-cancer drug S-1 for advanced gastro-intestinal cancer].

    PubMed

    Shirasaka, T; Aiba, K; Araki, H; Suzuki, M; Terashima, M; Mikami, Y

    1999-03-01

    Highly effective treatment is required for patients with advanced GI cancer. Returning to the starting point for reconsideration of cancer chemotherapy, with the aim of attaining a therapy (self rescuing concept: SRC) with more potential efficacy and less toxicity than current therapy, we report two kinds of chemotherapy in the present paper. They were set up preclinically using the theory of 5-FU biochemical modulation, and demonstrated their usefulness in clinical practice. S-1 is a newly developed oral anti-cancer drug which is a combination of Tegafur (FT), a prodrug of 5-FU and two modulators (CDHP, an inhibitor of 5-FU degradation and Oxo, a selective inhibitor GI toxicity by 5-FU) at a molar ratio of 1:0.4:1. In combination with CDHP, 5-FU gradually released from FT remained longer in plasma, and consequently had high anti-tumor activity, while the combined Oxo significantly suppressed GI toxicity due to 5-FU. The response rate to S-1 of stomach cancer in a phase II study was 46.5% (60/129). Toxicity at more than G3 was less than 10%. In the combination therapy employing 5-FU by CVI (5-FU: 250-350 mg/body for 24 h, 4-6 wks) and low dose consecutive CDDP, CDDP acts mainly as a modulator of 5-FU (to increase 5-FU sensitivity for tumor by inhibition of intracellular Met incorporation). For this purpose, it was found that daily consecutive administration is required, even at low dose of CDDP (3-5 mg/body/day for 5 days). A high response rate (40-60%) was obtained for advanced GI cancer. Toxicity at more than G3 was less than 10%. On the other hand, the possibility has been suggested that so far as 5-FU is concerned, CVI every other day (500-750 mg/body/day for 3 days) is more favorable than long term CVI, with regard to decreasing GI and myelotoxicities based upon the difference in generation time between normal cell (GI mucous membrane and stem cell) and tumor cell cycles. The possibility is suggested that the above-mentioned chemotherapy can become a standard

  9. Phase II trial of panitumumab with irinotecan as salvage therapy for patients with advanced or recurrent colorectal cancer (TOPIC study)

    PubMed Central

    NISHI, TOMOHIRO; HAMAMOTO, YASUO; NAGASE, MICHITAKA; DENDA, TADAMICHI; YAMAGUCHI, KENSEI; AMAGAI, KENJI; MIYATA, YOSHINORI; YAMANAKA, YASUHIRO; YANAI, KAI; ISHIKAWA, TSUTOMU; KUROKI, YOSHIFUMI; FUJII, HIROFUMI

    2016-01-01

    Little is known about the clinical impact of salvage panitumumab with irinotecan for metastatic colorectal cancer (mCRC) patients. The present study conducted a single-arm, multicenter phase II trial for mCRC with skin toxicity prevention program. The subjects were mCRC patients with wild-type KRAS, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan. Panitumumab was administered at a dose of 6 mg/kg every 2 weeks by intravenous infusion over 60 min, and irinotecan was administered at a dose of 100–180 mg/m2 every 2 weeks by intravenous infusion over 90 min, depending on the preceding treatment dose. To prevent skin toxicities, a moisturizer was applied and oral antibiotics (100 mg minocycline twice daily) were initiated for 6 weeks. The primary endpoint was the response rate (RR) determined by independent reviewers. Secondary endpoints were the disease control rate (DCR), progression-free survival (PFS) time, overall survival (OS) time and adverse events. A total of 35 patients were enrolled between October 2010 and March 2012. The median age was 61 years (range, 41–76 years), with 25 male and 10 female patients. The initial irinotecan dose was 150 mg/m2 in 19 patients and 180 mg/m2 in 1 patient. The remaining patients were treated with ≤120 mg/m2. A central review indicated a partial response in 8 patients (22.9%) and stable disease in 6 patients (17.1%), with an RR of 22.9% (95% confidence interval, 12.1–39.0) and a DCR of 40%. The RR of the patients with standard-dose irinotecan (150 or 180 mg/m2) was 30%, although that of low-dose irinotecan (100–120 mg/m2) was 13%. The median PFS time was 2.7 months, and the median OS time was 6.3 months. A grade 3 or above acne-like rash developed in 25.7% of patients. In conclusion, panitumumab and irinotecan as salvage therapy for mCRC KRAS wild-type patients with skin toxicity prevention exhibits limited efficacy. In particular, the effect of low-dose irinotecan with panitumumab appears to be

  10. Multifunctional Micellar Nanomedicine for Cancer Therapy

    PubMed Central

    Blanco, Elvin; Kessinger, Chase W.; Sumer, Baran D.; Gao, Jinming

    2010-01-01

    Polymeric micelles are supramolecular, core-shell nanoparticles that offer considerable advantages for cancer diagnosis and therapy. Their relatively small size (10-100 nm), ability to solubilize hydrophobic drugs as well as imaging agents, and improved pharmacokinetics provide a useful bioengineering platform for cancer applications. Several polymeric micelle formulations are currently undergoing phase I/II clinical trials, which have shown improved antitumor efficacy and reduced systemic toxicity. This minireview will focus on recent advancements in the multifunctional design of micellar nanomedicine with tumor targeting, stimulated drug release, and cancer imaging capabilities. Such functionalization strategies result in enhanced micellar accumulation at tumor sites, higher drug bioavailability, as well as improved tumor diagnosis and visualization of therapy. Ultimately, integrated nanotherapeutic systems (e.g., theranostic nanomedicine) may prove essential to address the challenges of tumor heterogeneity and adaptive resistance to achieve efficacious treatment of cancer. PMID:19064945

  11. Four-Week Neoadjuvant Intensity-Modulated Radiation Therapy With Concurrent Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer Patients: A Validation Phase II Trial

    SciTech Connect

    Arbea, Leire; Martinez-Monge, Rafael; Diaz-Gonzalez, Juan A.; Moreno, Marta; Rodriguez, Javier; Hernandez, Jose Luis; Sola, Jesus Javier; Ramos, Luis Isaac; Subtil, Jose Carlos; Nunez, Jorge; Chopitea, Ana; Cambeiro, Mauricio; Gaztanaga, Miren; Garcia-Foncillas, Jesus; Aristu, Javier

    2012-06-01

    Purpose: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. Methods and Materials: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m{sup 2} b.i.d., Monday to Friday) and oxaliplatin (60 mg/m{sup 2} on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. Results: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. Conclusions: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.

  12. [Clinical trials with advanced therapy medicinal products].

    PubMed

    Schüssler-Lenz, M; Schneider, C K

    2010-01-01

    For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.

  13. Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea

    PubMed Central

    Lim, Eun-A; Bae, Eunmi; Lim, Jaeok; Shin, Young Kee; Choi, Sang-Eun

    2016-01-01

    Background As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. Methods A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer’s perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). Results In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Conclusion Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy. PMID:27483001

  14. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... whether surgery will be helpful for you EXTERNAL BEAM RADIATION THER APY External beam radiation therapy is the safe delivery of high- ... your cancer. A linear accelerator focuses the radiation beam to a precise location in your body for ...

  15. Chemosensory alterations and cancer therapies

    SciTech Connect

    Bartoshuk, L.M. )

    1990-01-01

    Taste and olfaction provide sensory information and sensory pleasure. Cancer therapies affect both. Chemotherapy has not been shown to produce dramatic losses of taste or smell, but systematic studies on various chemotherapeutic agents and types of cancer are lacking. Radiation therapy does produce clear losses of both taste and smell. Both chemotherapy and radiation therapy alter the pleasure produced by taste and smell through the formation of conditioned aversions. That is, foods consumed in proximity with the nausea of therapy come to be unpleasant. The impact of conditioned aversions can be diminished by providing a scapegoat food just before therapy. Alterations in foods may be beneficial to the cancer patient. Increasing the concentrations of flavor ingredients can compensate for sensory losses, and providing pureed foods that retain the cognitive integrity of a meal can benefit the patient who has chewing or swallowing problems.

  16. Adding Targeted Therapy to Treatment for Esophageal Cancer

    Cancer.gov

    In this phase III clinical trial, people with confirmed HER2-positive locally advanced esophageal cancer will be randomly assigned to receive preoperative radiation therapy and chemotherapy, with or without trastuzumab.

  17. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect

    Feddock, Jonathan; Arnold, Susanne M.; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  18. Clinical Usefulness of {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography in Patients With Locally Advanced Pancreatic Cancer Planned to Undergo Concurrent Chemoradiation Therapy

    SciTech Connect

    Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin; Kim, Kyung Hwan; Park, Jeong Youp; Song, Si Young; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Seong, Jinsil

    2014-09-01

    Purpose: To assess the role of coregistered {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials: From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results: FDG-PET detected unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) <3.5 and/or SUV decline ≥60% had significantly better OS and PFS than those having none, even after adjustment for all potential confounding variables (all P<.001). Conclusions: FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.

  19. Targeted cancer therapy; nanotechnology approaches for overcoming drug resistance.

    PubMed

    Gao, Yan; Shen, Jacson K; Milane, Lara; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

    2015-01-01

    Recent advances in cancer molecular biology have resulted in parallel and unprecedented progress in the development of targeted cancer therapy. Targeted therapy can provide higher efficacy and lower toxicity than conventional chemotherapy for cancer. However, like traditional chemotherapy, molecularly targeted cancer therapy also faces the challenge of drug resistance. Multiple mechanisms are responsible for chemotherapy resistance in tumors, including over-expression of efflux transporters, somatic alterations of drug targets, deregulation of apoptosis, and numerous pharmacokinetic issues. Nanotechnology based approaches are proving to be efficacious in overcoming drug resistance in cancer. Combination of targeted therapies with nanotechnology approaches is a promising strategy to overcome targeted therapy drug resistance in cancer treatment. This review discusses the mechanisms of targeted drug resistance in cancer and discusses nanotechnology approaches to circumvent this resistance.

  20. Recent advances in migraine therapy.

    PubMed

    Antonaci, Fabio; Ghiotto, Natascia; Wu, Shizheng; Pucci, Ennio; Costa, Alfredo

    2016-01-01

    Migraine is a common and highly disabling neurological disorder associated with a high socioeconomic burden. Effective migraine management depends on adequate patient education: to avoid unrealistic expectations, the condition must be carefully explained to the patient soon as it is diagnosed. The range of available acute treatments has increased over time. At present, abortive migraine therapy can be classed as specific (ergot derivatives and triptans) or non-specific (analgesics and non-steroidal anti-inflammatory drugs). Even though acute symptomatic therapy can be optimised, migraine continues to be a chronic and potentially progressive condition. In addition to the drugs officially approved for migraine prevention by international governmental regulatory agencies, numerous different agents are commonly used for this indication, showing various levels of evidence of efficacy and tolerability. Guidelines published in recent years, based on evidence-based medicine data on migraine prophylaxis, are a useful source of guidance, especially for primary care physicians and neurologists without specific expertise in headache medicine. Although the field of pharmacological migraine prevention has seen few advances in recent years, potential novel approaches are now being developed. This review looks at emerging pharmacological strategies for acute and preventive migraine treatment that are nearing or have already entered the clinical trial phase. Specifically, it discusses preclinical and clinical data on compounds acting on calcitonin gene-related peptide or its receptor, the serotonin 5-HT1F receptor, nitric oxide synthase, and acid-sensing ion channel blockers. PMID:27330903

  1. Adjuvant Endocrine Therapy in Premenopausal Women with Breast Cancer

    PubMed Central

    Kadakia, Kunal C.; Henry, N. Lynn

    2016-01-01

    Breast cancer remains the leading cause of cancer related mortality in premenopausal women. Multiple advances in local and systemic therapies have dramatically improved outcomes in women with HR+ early stage breast cancer. Despite these advances, early and late relapses occur. Therefore multiple adjuvant endocrine therapy trials have been conducted with the goal of decreasing breast cancer recurrence and mortality. Recently, large international trials evaluating extended endocrine therapy as well as ovarian suppression with and without tamoxifen or exemestane have been reported. These studies add to the large body of existing data related to adjuvant endocrine therapy in premenopausal women with breast cancer and provide additional therapeutic options in those at high risk of disease recurrence. This review will synthesize the most recent data and provide an evidenced based approach, highlighting quality-of-life concerns, when considering adjuvant endocrine therapies in premenopausal women. PMID:27058571

  2. Dendritic cell vaccine and cytokine-induced killer cell therapy for the treatment of advanced non-small cell lung cancer

    PubMed Central

    ZHANG, LIHONG; YANG, XUEJING; SUN, ZHEN; LI, JIALI; ZHU, HUI; LI, JING; PANG, YAN

    2016-01-01

    The present study aimed to evaluate the survival time, immune response and safety of a dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy (DC-CIK) in advanced non-small cell lung cancer (NSCLC). The present retrospective study enrolled 507 patients with advanced NSCLC; 99 patients received DC-CIK [immunotherapy group (group I)] and 408 matched patients did not receive DC-CIK, and acted as the control [non-immunotherapy group (group NI)]. Delayed-type hypersensitivity (DTH), quality of life (QOL) and safety were analyzed in group I. The follow-up period for the two groups was 489.2±160.4 days. The overall survival (OS) time was calculated using the Kaplan-Meier method. DTH was observed in 59 out of 97 evaluated patients (60.8%) and 67 out of 98 evaluated patients (68.4%) possessed an improved QOL. Fever and a skin rash occurred in 36 out of 98 patients (36.7%) and 7 out of 98 patients (7.1%) in group I. DTH occurred more frequently in patients with squamous cell carcinoma compared with patients with adenocarcinoma (77.1 vs. 40.4%; P=0.0013). Radiotherapy was not associated with DC-CIK-induced DTH (72.7 vs. 79.6%; P=0.18), but chemotherapy significantly reduced the rate of DTH (18.2 vs. 79.6%; P=0.00). The OS time was significantly increased in group I compared with group NI (P=0.03). In conclusion, DC-CIK may induce an immune response against NSCLC, improve the QOL, and prolong the OS time of patients, without adverse effects. Therefore, the present study recommends DC-CIK for the treatment of patients with advanced NSCLC. PMID:27073525

  3. Neurotoxicity Associated With Cancer Therapy

    PubMed Central

    Lu Lee, Eva; Westcarth, Laurel

    2012-01-01

    Neurologic complications can result from direct or indirect effects of cancer therapy. Treatment toxicity may affect both the central nervous system and the peripheral nervous system. Early recognition of these toxicities plays an important role in the management of patients with cancer. PMID:25031923

  4. Management of advanced medullary thyroid cancer.

    PubMed

    Hadoux, Julien; Pacini, Furio; Tuttle, R Michael; Schlumberger, Martin

    2016-01-01

    Medullary thyroid cancer arises from calcitonin-producing C-cells and accounts for 3-5% of all thyroid cancers. The discovery of a locally advanced medullary thyroid cancer that is not amenable to surgery or of distant metastases needs careful work-up, including measurement of serum calcitonin and carcinoembryonic antigen (and their doubling times), in addition to comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for any treatment. In the past, cytotoxic chemotherapy was used for treatment but produced little benefit. For the past 10 years, tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors and RET (rearranged during transfection) have been used when a systemic therapy is indicated for large tumour burden and documented disease progression. Vandetanib and cabozantinib have shown benefits on progression-free survival compared with placebo in this setting, but their toxic effect profiles need thorough clinical management in specialised centres. This Review describes the management and treatment of patients with advanced medullary thyroid cancer with emphasis on current targeted therapies and perspectives to improve patient care. Most treatment responses are transient, emphasising that mechanisms of resistance need to be better understood and that the efficacy of treatment approaches should be improved with combination therapies or other drugs that might be more potent or target other pathways, including immunotherapy. PMID:26608066

  5. Laser therapy for cancer

    MedlinePlus

    Compared to surgery, laser therapy has some benefits. Laser therapy: Takes less time Is more precise and causes less damage to tissues Leads to less pain, bleeding, infections, and scarring Can often be done ...

  6. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  7. Cancer Alternative Therapies

    MedlinePlus

    You have many choices to make about your cancer treatment. One choice you might be thinking about ... are acupuncture, chiropractic, and herbal medicines. People with cancer may use CAM to Help cope with the ...

  8. [Radionuclide therapy of endocrine-related cancer].

    PubMed

    Kratochwil, C; Giesel, F L

    2014-10-01

    This article gives an overview of the established radionuclide therapies for endocrine-related cancer that already have market authorization or are currently under evaluation in clinical trials. Radioiodine therapy is still the gold standard for differentiated iodine-avid thyroid cancer. In patients with bone and lung metastases (near) total remission is seen in approximately 50% and the 15-year survival rate for these patients is approximately 90%. In contrast to the USA, meta-iodobenzylguanidine (MIBG) therapy has market approval in Europe. According to the current literature, in the setting of advanced stage neuroblastoma and malignant pheochromocytoma or paraganglioma, radiological remission can be achieved in >30% and symptom control in almost 80% of the treated patients. Somatostatin receptor targeted radionuclide therapies (e.g. with DOTATATE or DOTATOC) demonstrated promising results in phase 2 trials, reporting progression-free survival in the range of 24-36 months. A first phase 3 pivotal trial for intestinal carcinoids is currently recruiting and another trial for pancreatic neuroendocrine tumors is planned. Radiopharmaceuticals based on glucagon-like peptide 1 (GLP1) or minigastrins are in the early evaluation stage for application in the treatment of insulinomas and medullary thyroid cancer. In general, radiopharmaceutical therapy belongs to the group of so-called theranostics which means that therapy is tailored for individual patients based on molecular imaging diagnostics to stratify target positive or target negative tumor phenotypes.

  9. Stereotactic Body Radiation Therapy for Pancreatic Cancer.

    PubMed

    Goodman, Karyn A

    2016-01-01

    The role of radiation therapy in the management of pancreatic cancer represents an area of some controversy. However, local disease progression remains a significant cause of morbidity and even mortality for patients with this disease. Stereotactic body radiotherapy (SBRT) is an emerging treatment option for pancreatic cancer, primarily for locally advanced (unresectable) disease as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation. There may also be a role for SBRT as neoadjuvant therapy for patients with borderline resectable disease to allow conversion to resectability. The objective of this review is to present the data supporting SBRT in pancreatic cancer as well as the potential limitations and caveats of current studies.

  10. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  11. [Genetic basis of head and neck cancers and gene therapy].

    PubMed

    Özel, Halil Erdem; Özkırış, Mahmut; Gencer, Zeliha Kapusuz; Saydam, Levent

    2013-01-01

    Surgery and combinations of traditional treatments are not successful enough particularly for advanced stage head and neck cancer. The major disadvantages of chemotherapy and radiation therapy are the lack of specificity for the target tissue and toxicity to the patient. As a result, gene therapy may offer a more specific approach. The aim of gene therapy is to present therapeutic genes into cancer cells which selectively eliminate malignant cells with no systemic toxicity to the patient. This article reviews the genetic basis of head and neck cancers and important concepts in cancer gene therapy: (i) inhibition of oncogenes; (ii) tumor suppressor gene replacement; (iii) regulation of immune response against malignant cells; (iv) genetic prodrug activation; and (v) antiangiogenic gene therapy. Currently, gene therapy is not sufficient to replace the traditional treatments of head and neck cancers, however there is no doubt that it will have an important role in the near future.

  12. Targeted Therapy in Nonmelanoma Skin Cancers

    PubMed Central

    Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio

    2011-01-01

    Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC. PMID:24212808

  13. Surgical management of advanced gastric cancer: An evolving issue.

    PubMed

    Marano, L; Polom, K; Patriti, A; Roviello, G; Falco, G; Stracqualursi, A; De Luca, R; Petrioli, R; Martinotti, M; Generali, D; Marrelli, D; Di Martino, N; Roviello, F

    2016-01-01

    Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer. PMID:26632080

  14. Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study

    PubMed Central

    Campbell, Toby C.; Zhang, Chong; Kim, KyungMann; Kolesar, Jill M.; Oettel, Kurt R.; Blank, Jules H.; Robinson, Emily G.; Ahuja, Harish G.; Kirschling, Ron J.; Johnson, Peter H.; Huie, Michael S.; Wims, Mary E.; Larson, Martha M.; Hernan, Hilary R.; Traynor, Anne M.

    2014-01-01

    Summary Introduction The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. Methods Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0–2. Patients took vorinostat 400 mg PO daily days 1–14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. Results Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1–6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. Conclusions Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients. PMID:23728919

  15. Extended Intervals after Neoadjuvant Therapy in Locally Advanced Rectal Cancer: The Key to Improved Tumor Response and Potential Organ Preservation

    PubMed Central

    Probst, Christian P; Becerra, Adan Z; Aquina, Christopher T; Tejani, Mohamedtaki A; Wexner, Steven D; Garcia-Aguilar, Julio; Remzi, Feza H; Dietz, David W; Monson, John RT; Fleming, Fergal J

    2016-01-01

    Background Many rectal cancer patients experience tumor downstaging and some are found to achieve a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Previous data suggest that there is an association between the time interval from nCRT completion to surgery and tumor response rates, including pCR. However, these studies have been primarily from single institutions with small sample sizes. The aim of this study was to examine the relationship between a longer interval after nCRT and pCR in a nationally representative cohort of rectal cancer patients. Study Design Clinical stage II–III rectal cancer patients undergoing nCRT with a documented surgical resection were selected from the 2006 – 2011 National Cancer Data Base. Multivariable logistic regression analysis was used to assess the association between nCRT-surgery interval time (<6 weeks, 6–8 weeks, >8 weeks) and the odds of pCR. The relationship between nCRT-surgery interval, surgical morbidity, and tumor downstaging was also examined. Results Overall, 17,255 patients met the inclusion criteria. A nCRT-surgery interval time >8 weeks was associated with higher odds of pCR (OR=1.12, 95%CI=1.01–1.25) and tumor downstaging (OR=1.11, 95%CI =1.02–1.25). The longer time delay was also associated with lower odds of 30-day readmission (OR=0.82, 95%CI: 0.70–0.92). Conclusions A nCRT-surgery interval time >8 weeks results in increased odds of pCR with no evidence of associated increased surgical complications compared to 6–8 weeks. This data supports the implementation of a lengthened interval after nCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation (non-operative management). PMID:26206642

  16. Direct therapeutic intervention for advanced pancreatic cancer.

    PubMed

    Takakura, Kazuki; Koido, Shigeo

    2015-12-10

    Currently, chemotherapy is an accredited, standard treatment for unresectable, advanced pancreatic cancer (PC). However, it has been still showed treatment-resistance and followed dismal prognosis in many cases. Therefore, some sort of new, additional treatments are needed for the better therapeutic results for advanced PC. According to the previous reports, it is obvious that interventional endoscopic ultrasonography (EUS) is a well-established, helpful and low-risky procedure in general. As the additional treatments of the conventional therapy for advanced PC, many therapeutic strategies, such as immunotherapies, molecular biological therapies, physiochemical therapies, radioactive therapies, using siRNA, using autophagy have been developing in recent years. Moreover, the efficacy of the other potential therapeutic targets for PC using EUS-fine needle injection, for example, intra-tumoral chemotherapeutic agents (paclitaxel, irinotecan), several ablative energies (radiofrequency ablation and cryothermal treatment, neodymium-doped yttrium aluminum garnet laser, high-intensity focused ultrasound), etc., has already been showed in animal models. Delivering these promising treatments reliably inside tumor, interventional EUS may probably be indispensable existence for the treatment of locally advanced PC in near future. PMID:26677434

  17. Direct therapeutic intervention for advanced pancreatic cancer

    PubMed Central

    Takakura, Kazuki; Koido, Shigeo

    2015-01-01

    Currently, chemotherapy is an accredited, standard treatment for unresectable, advanced pancreatic cancer (PC). However, it has been still showed treatment-resistance and followed dismal prognosis in many cases. Therefore, some sort of new, additional treatments are needed for the better therapeutic results for advanced PC. According to the previous reports, it is obvious that interventional endoscopic ultrasonography (EUS) is a well-established, helpful and low-risky procedure in general. As the additional treatments of the conventional therapy for advanced PC, many therapeutic strategies, such as immunotherapies, molecular biological therapies, physiochemical therapies, radioactive therapies, using siRNA, using autophagy have been developing in recent years. Moreover, the efficacy of the other potential therapeutic targets for PC using EUS-fine needle injection, for example, intra-tumoral chemotherapeutic agents (paclitaxel, irinotecan), several ablative energies (radiofrequency ablation and cryothermal treatment, neodymium-doped yttrium aluminum garnet laser, high-intensity focused ultrasound), etc., has already been showed in animal models. Delivering these promising treatments reliably inside tumor, interventional EUS may probably be indispensable existence for the treatment of locally advanced PC in near future. PMID:26677434

  18. Problems of intensive therapy in childhood cancer

    SciTech Connect

    Skelton, J.; Pizzo, P.A.

    1986-07-15

    Tremendous progress has been made in the treatment of childhood cancers. Certain hematologic malignancies have an impressive cure rate with the current intensive antineoplastic treatment regimens. There is optimism that the treatment of children who have advanced stage solid tumors with intensive, multimodality therapy may improve their chances for long-term survival. These treatment programs, though potentially curative, are highly toxic, with severe myelosuppression and damage to other organ systems. An awareness of these potential toxicities, an understanding of how to prevent or minimize certain problems, and the ability to treat those complications which do arise are all essential to the successful management of childhood cancer. 206 references.

  19. New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

    PubMed Central

    Kamdje, Armel Hervé Nwabo; Etet, Paul Faustin Seke; Vecchio, Lorella; Tagne, Richard Simo; Amvene, Jeremie Mbo; Muller, Jean-Marc; Krampera, Mauro; Lukong, Kiven Erique

    2014-01-01

    Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy, including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin, Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed. PMID:25516852

  20. Systemic cancer therapy: achievements and challenges that lie ahead.

    PubMed

    Palumbo, Michael O; Kavan, Petr; Miller, Wilson H; Panasci, Lawrence; Assouline, Sarit; Johnson, Nathalie; Cohen, Victor; Patenaude, Francois; Pollak, Michael; Jagoe, R Thomas; Batist, Gerald

    2013-01-01

    In the last half of the century, advances in the systemic therapy of cancer, including chemotherapy, hormonal therapy, targeted therapy, and immunotherapy have been responsible for improvements in cancer related mortality in developed countries even as the population continues to age. Although such advancements have yet to benefit all cancer types, systemic therapies have led to an improvement in overall survival in both the adjuvant and metastatic setting for many cancers. With the pressure to make therapies available as soon as possible, the side-effects of systemic therapies, in particular long-term side-effects are not very well characterized and understood. Increasingly, a number of cancer types are requiring long-term and even lifelong systemic therapy. This is true for both younger and older patients with cancer and has important implications for each subset. Younger patients have an overall greater expected life-span, and as a result may suffer a greater variety of treatment related complications in the long-term, whereas older patients may develop earlier side-effects as a result of their frailty. Because the incidence of cancer in the world will increase over the next several decades and there will be more people living with cancer, it is important to have an understanding of the potential side-effects of new systemic therapies. As an introductory article, in this review series, we begin by describing some of the major advances made in systemic cancer therapy along with some of their known side-effects and we also make an attempt to describe the future of systemic cancer therapy.

  1. Therapeutic Antibodies in Cancer Therapy.

    PubMed

    Gasser, Martin; Waaga-Gasser, Ana Maria

    2016-01-01

    The therapeutic arsenal in solid tumors comprises different anticancer strategies with diverse chemotherapeutic agents and a growing number of biological substances. Large clinical study-based chemotherapeutic protocols combined with biologicals have become an important component in (neo-) adjuvant therapy alongside surgery in solid cancers as well as radiation therapy in some instances. In recent years, monoclonal antibodies have entered the mainstream of cancer therapy. Their first use was as antagonists of oncogenic receptor tyrosine kinases, but today monoclonal antibodies have emerged as long-sought vehicles for the targeted delivery of potent chemotherapeutic agents and as powerful tools to manipulate anticancer immune responses. There is a growing number of FDA approved monoclonal antibodies and small molecules targeting specific types of cancer suggestive of the clinical relevance of this approach.Targeted cancer therapies , also referred to as personalized medicine, are being studied for use alone, in combination with other targeted therapies, and in combination with chemotherapy. The use of monoclonal antibodies in colorectal and gastric cancer for example have shown best outcome when combined with chemotherapy, even though single agent anti-EGFR antibodies seem to be active in particular setting of metastatic colorectal cancer patients. However, it is not well defined whether the addition of anti-VEGF - and anti-EGFR strategies to chemotherapy could improve outcome in those patients susceptible to colorectal cancer-related metastases resection. Among the most promising approaches to activating therapeutic antitumor immunity is the blockade of immune checkpoints, exemplified by the recently FDA-approved agent, Ipilimumab, an antibody that blocks the coinhibitory receptor CTLA-4. Capitalizing on the success of Ipilimumab, agents that target a second coinhibitory receptor, PD-1, or its ligand, PD-L1, are in clinical development. This section attempts to

  2. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    SciTech Connect

    Dholakia, Avani S.; Chaudhry, Muhammad; Leal, Jeffrey P.; Chang, Daniel T.; Raman, Siva P.; Hacker-Prietz, Amy; Su, Zheng; Pai, Jonathan; Oteiza, Katharine E.; Griffith, Mary E.; Wahl, Richard L.; Tryggestad, Erik; Pawlik, Timothy; Laheru, Daniel A.; Wolfgang, Christopher L.; Koong, Albert C.; and others

    2014-07-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in

  3. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Hong, C; Ju, S; Ahn, Y

    2015-06-15

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.

  4. Simultaneous integrated boost plan comparison of volumetric-modulated arc therapy and sliding window intensity-modulated radiotherapy for whole pelvis irradiation of locally advanced prostate cancer.

    PubMed

    Riou, Olivier; Regnault de la Mothe, Pauline; Azria, David; Aillères, Norbert; Dubois, Jean-Bernard; Fenoglietto, Pascal

    2013-07-08

    Concurrent radiotherapy to the pelvis plus a prostate boost with long-term androgen deprivation is a standard of care for locally advanced prostate cancer. IMRT has the ability to deliver highly conformal dose to the target while lowering irradiation of critical organs around the prostate. Volumetric-modulated arc therapy is able to reduce treatment time, but its impact on organ sparing is still controversial when compared to static gantry IMRT. We compared the two techniques in simultaneous integrated boost plans. Ten patients with locally advanced prostate cancer were included. The planning target volume (PTV) 1 was defined as the pelvic lymph nodes, the prostate, and the seminal vesicles plus setup margins. The PTV2 consisted of the prostate with setup margins. The prescribed doses to PTV1 and PTV2 were 54 Gy in 37 fractions and 74 Gy in 37 fractions, respectively. We compared simultaneous integrated boost plans by means of either a seven coplanar static split fields IMRT, or a one-arc (RA1) and a two-arc (RA2) RapidArc planning. All three techniques allowed acceptable homogeneity and PTV coverage. Static IMRT enabled a better homogeneity for PTV2 than RapidArc techniques. Sliding window IMRT and VMAT permitted to maintain doses to OAR within acceptable levels with a low risk of side effects for each organ. VMAT plans resulted in a clinically and statistically significant reduction in doses to bladder (mean dose IMRT: 50.1 ± 4.6Gy vs. mean dose RA2: 47.1 ± 3.9 Gy, p = 0.037), rectum (mean dose IMRT: 44± 4.5 vs. mean dose RA2: 41.6 ± 5.5 Gy, p = 0.006), and small bowel (V30 IMRT: 76.47 ± 14.91% vs. V30 RA2: 47.49 ± 16.91%, p = 0.002). Doses to femoral heads were higher with VMAT but within accepted constraints. Our findings suggest that simultaneous integrated boost plans using VMAT and sliding window IMRT allow good OAR sparing while maintaining PTV coverage within acceptable levels.

  5. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048

  6. Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

    SciTech Connect

    Gao, Yuan-Hong; Lin, Jun-Zhong; An, Xin; Luo, Jie-Lin; Cai, Mu-Yan; Cai, Pei-Qiang; Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2014-12-01

    Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen

  7. Hesperetin Liposomes for Cancer Therapy.

    PubMed

    Wolfram, Joy; Scott, Bronwyn; Boom, Kathryn; Shen, Jianliang; Borsoi, Carlotta; Suri, Krishna; Grande, Rossella; Fresta, Massimo; Celia, Christian; Zhao, Yuliang; Shen, Haifa; Ferrari, Mauro

    2016-01-01

    Hesperetin is a compound from citrus fruit that has previously been found to exert anticancer activity through a variety of mechanisms. However, the application of hesperetin to cancer therapy has been hampered by its hydrophobicity, necessitating the use of toxic solubilizing agents. Here, we have developed the first liposome-based delivery system for hesperetin. Liposomes were fabricated using the thin-layer evaporation technique and physical and pharmacological parameters were measured. The liposomes remained stable for prolonged periods of time in serum and under storage conditions, and displayed anticancer efficacy in both H441 lung cancer cells and MDA-MB-231 breast cancer cells. Furthermore, the anticancer activity was not impaired in cells expressing the multidrug resistance protein 1 (MDR-1). In conclusion, the encapsulation of hesperetin in liposomes does not interfere with therapeutic efficacy and provides a biocompatible alternative to toxic solubilizing agents, thereby enabling future clinical use of this compound for cancer therapy.

  8. Oral targeted therapy for cancer

    PubMed Central

    Carrington, Christine

    2015-01-01

    SUMMARY Oral targeted therapies are increasingly being used to treat cancer. They work by interfering with specific molecules or pathways involved in tumour growth. It is essential that health professionals managing patients taking these drugs have appropriate training and skills. They should be aware of potential adverse effects and drug interactions, and be able to manage toxicities when they occur. Despite the selectivity of these targeted therapies, they still have serious adverse effects including skin reactions, diarrhoea and altered organ function. PMID:26648656

  9. Radiation Therapy and You: Support for People with Cancer

    MedlinePlus

    ... Support for Caregivers Survivorship Questions to Ask About Cancer Research Advanced Cancer Choices for Care Talking about Advanced ... Cancer and Caregivers Questions to Ask about Advanced Cancer Research Managing Cancer Care Finding Health Care Services Advance ...

  10. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy: Result from 3 clinical trials of advanced NSCLC by 1 institution.

    PubMed

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-08-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC.A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria.Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ -8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) -8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS (HR, 2.36, 95

  11. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  12. Targeting antioxidants for cancer therapy.

    PubMed

    Glasauer, Andrea; Chandel, Navdeep S

    2014-11-01

    Cancer cells are characterized by an increase in the rate of reactive oxygen species (ROS) production and an altered redox environment compared to normal cells. Furthermore, redox regulation and redox signaling play a key role in tumorigenesis and in the response to cancer therapeutics. ROS have contradictory roles in tumorigenesis, which has important implications for the development of potential anticancer therapies that aim to modulate cellular redox levels. ROS play a causal role in tumor development and progression by inducing DNA mutations, genomic instability, and aberrant pro-tumorigenic signaling. On the other hand, high levels of ROS can also be toxic to cancer cells and can potentially induce cell death. To balance the state of oxidative stress, cancer cells increase their antioxidant capacity, which strongly suggests that high ROS levels have the potential to actually block tumorigenesis. This fact makes pro-oxidant cancer therapy an interesting area of study. In this review, we discuss the controversial role of ROS in tumorigenesis and especially elaborate on the advantages of targeting ROS scavengers, hence the antioxidant capacity of cancer cells, and how this can be utilized for cancer therapeutics.

  13. Androgen deprivation therapy for prostate cancer.

    PubMed

    Singer, Eric A; Golijanin, Dragan J; Miyamoto, Hiroshi; Messing, Edward M

    2008-02-01

    Androgen deprivation continues to play a crucial role in the treatment of advanced and metastatic prostate cancer. In the 65 years since its use was first described, urologists and medical oncologists have developed new and innovative ways to manipulate the hypothalamic-pituitary-gonadal axis with the goal of alleviating symptoms and prolonging the life of men with prostate cancer. Despite the successes that androgen deprivation therapy has brought, each method and regimen possesses unique benefits and burdens, of which the clinician and patient must be cognizant. This review discusses the first-line androgen deprivation methods and regimens presently in use with special attention paid to their side effects and the management of them, as well as the question of when to initiate androgen deprivation therapy.

  14. Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. Epidemiology of skin cancer in solid organ transplant recipients.

    PubMed

    Zwald, Fiona O'Reilly; Brown, Marc

    2011-08-01

    Skin cancer is the most frequent malignancy in organ transplant recipients, 95% of which are nonmelanoma skin cancer, especially squamous cell and basal cell carcinomas. This paper also discusses the incidence of other tumors (eg, melanoma, Merkel cell carcinoma, and Kaposi sarcoma) that are also increased in organ transplant patients compared to the general population. Part I of this two-part series describes the latest data concerning the epidemiologic and pathogenic aspects of nonmelanoma skin cancer development in solid organ transplant recipients. This review also highlights the concept of "field cancerization," represented by extensive areas of actinic damage and epidermal dysplasia, which accounts for increased risk of aggressive skin cancer development in susceptible patients. PMID:21763561

  15. Nanocarrier mediated Delivery of siRNA/miRNA in Combination with Chemotherapeutic Agents for Cancer Therapy: Current Progress and Advances

    PubMed Central

    Gandhi, Nishant S.; Tekade, Rakesh K.; Chougule, Mahavir B.

    2014-01-01

    Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibits drug resistance due to activation of various cellular level processes viz. activation of drug efflux pumps, anti-apoptotic defense mechanisms etc. Currently, RNA interference (RNAi) based therapeutic approaches are under vibrant scrutinization to seek cancer cure. Especially small interfering RNA (siRNA) and micro RNA (miRNA), are able to knock down the carcinogenic genes by targeting the mRNA expression, which underlies the uniqueness of this therapeutic approach. Recent research focus in the regime of cancer therapy involves the engagement of targeted delivery of siRNA/miRNA in combinations with other therapeutic agents (such as gene, DNA or chemotherapeutic drug) for targeting permeability glycoprotein (P-gp), Multidrug resistant protein 1(MRP-1), B-cell lymphoma (BCL-2) and other targets that are mainly responsible for resistance in cancer therapy. RNAi-chemotherapeutic drug combinations have also been found to be effective against different molecular targets as well and can increase the sensitization of cancer cells to therapy several folds. However, due to stability issues associated with siRNA/miRNA suitable protective carrier is needed and nanotechnology based approaches have been widely explored to overcome these drawbacks. Furthermore, it has been univocally advocated that the co-delivery of siRNA/miRNA with other chemodrugs significantly enhances their capability to overcome cancer resistance compared to naked counterparts. The objective of this article is to review recent nanocarrier based approaches adopted for the delivery of siRNA/miRNA combinations with other anticancer agents (siRNA/miRNA/pDNA/chemodrugs) to treat cancer. PMID:25204288

  16. Stimuli-responsive polymersomes for cancer therapy.

    PubMed

    Thambi, Thavasyappan; Park, Jae Hyung; Lee, Doo Sung

    2016-01-01

    Cancer is the leading cause of mortality and remains a major challenge for modern chemotherapy. Recent advances in cancer therapy have made a modest impact on patient survival. Nanomedicine represents an innovative field with significant potential to improve cancer treatment. Nanomedicine utilizes numerous nanoconstructs, including polymersomes, micelles, and drug conjugates, to deliver therapeutic agents at the target site of interest. In particular, polymeric vesicles, also known as polymersomes, are self-assembled amphiphilic polymers in which an aqueous compartment is enclosed by a thick bilayer membrane. Unlike liposomes, polymersomes consist of high-molecular-weight amphiphilic polymer analogues. Since polymersomes are prepared using synthetic amphiphilic polymers, the bilayer membrane thickness can be readily altered by tuning the molecular weight of hydrophobic blocks. As a consequence, the polymersomes prepared from high-molecular-weight amphiphiles strengthen their membranes, making them inherently more stable than liposomes. The intriguing aggregation of polymersomes offers numerous advantages, including stability, tunable membrane properties, and the capability of encapsulating hydrophilic and hydrophobic agents. Owing to these properties, polymersomes are attractive candidates for various applications such as drug delivery, gene therapy, and tissue engineering. Although these properties have placed polymersomes at the forefront of drug delivery applications, to attain an enhanced therapeutic effect polymersomes are supposed to rapidly release the drug at the target site. To fulfill this requirement, stimuli-responsive polymersomes that respond to various internal or external stimuli have been developed. This review focuses on recently developed stimuli-responsive polymersomes and their potential application in cancer therapy.

  17. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

    SciTech Connect

    Alberda, Wijnand J.; Verhoef, Cornelis; Nuyttens, Joost J.; Meerten, Esther van; Rothbarth, Joost; Wilt, Johannes H.W. de; Burger, Jacobus W.A.

    2014-04-01

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.

  18. Advances in genetics: widening our understanding of prostate cancer

    PubMed Central

    Pine, Angela C.; Fioretti, Flavia F.; Brooke, Greg N.; Bevan, Charlotte L.

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate cancer through the application of whole-exome sequencing, and this review summarises recent advances in this field and discusses how exome sequencing could be used clinically to promote personalised medicine for prostate cancer patients. PMID:27408704

  19. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    SciTech Connect

    Higuchi, Katsuhiko; Komori, Shouko; Tanabe, Satoshi; Katada, Chikatoshi; Azuma, Mizutomo; Ishiyama, Hiromichi; Sasaki, Tohru; Ishido, Kenji; Katada, Natsuya; Hayakawa, Kazushige; Koizumi, Wasaburo

    2014-07-15

    Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m{sup 2}) and cisplatin (40 mg/m{sup 2}) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.

  20. Peptide-Based Treatment: A Promising Cancer Therapy

    PubMed Central

    Xiao, Yu-Feng; Jie, Meng-Meng; Li, Bo-Sheng; Hu, Chang-Jiang; Xie, Rui; Tang, Bo; Yang, Shi-Ming

    2015-01-01

    Many new therapies are currently being used to treat cancer. Among these new methods, chemotherapy based on peptides has been of great interest due to the unique advantages of peptides, such as a low molecular weight, the ability to specifically target tumor cells, and low toxicity in normal tissues. In treating cancer, peptide-based chemotherapy can be mainly divided into three types, peptide-alone therapy, peptide vaccines, and peptide-conjugated nanomaterials. Peptide-alone therapy may specifically enhance the immune system's response to kill tumor cells. Peptide-based vaccines have been used in advanced cancers to improve patients' overall survival. Additionally, the combination of peptides with nanomaterials expands the therapeutic ability of peptides to treat cancer by enhancing drug delivery and sensitivity. In this review, we mainly focus on the new advances in the application of peptides in treating cancer in recent years, including diagnosis, treatment, and prognosis. PMID:26568964

  1. Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck

    SciTech Connect

    Tishler, Roy B. . E-mail: roy_tishler@dfci.harvard.edu; Posner, Marshall R.; Norris, Charles M.; Mahadevan, Anand; Sullivan, Christopher; Goguen, Laura; Wirth, Lori J.; Costello, Rosemary; Case, MaryAnn; Stowell, Sara; Sammartino, Dan; Busse, Paul M.; Haddad, Robert I.

    2006-07-15

    Purpose: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. Patients and Methods: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M{sup 2} and 25 mg/M{sup 2}. Results: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. Conclusions: This intensive treatment regimen of concurrent docetaxel/concomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to

  2. Diffuse Optical Monitoring of the Neoadjuvant Breast Cancer Therapy

    PubMed Central

    Choe, Regine; Durduran, Turgut

    2012-01-01

    Recent advances in the use of diffuse optical techniques for monitoring the hemodynamic, metabolic and physiological signatures of the neoadjuvant breast cancer therapy effectiveness is critically reviewed. An extensive discussion of the state-of-theart diffuse optical mammography is presented alongside a discussion of the current approaches to breast cancer therapies. Overall, the diffuse optics field is growing rapidly with a great deal of promise to fill an important niche in the current approaches to monitor, predict and personalize neoadjuvant breast cancer therapies. PMID:23243386

  3. Diffuse Optical Monitoring of the Neoadjuvant Breast Cancer Therapy.

    PubMed

    Choe, Regine; Durduran, Turgut

    2012-07-01

    Recent advances in the use of diffuse optical techniques for monitoring the hemodynamic, metabolic and physiological signatures of the neoadjuvant breast cancer therapy effectiveness is critically reviewed. An extensive discussion of the state-of-theart diffuse optical mammography is presented alongside a discussion of the current approaches to breast cancer therapies. Overall, the diffuse optics field is growing rapidly with a great deal of promise to fill an important niche in the current approaches to monitor, predict and personalize neoadjuvant breast cancer therapies.

  4. Long-Term Follow-Up of Preoperative Pelvic Radiation Therapy and Concomitant Boost Irradiation in Locally Advanced Rectal Cancer Patients: A Multi-Institutional Phase II Study (KROG 04-01)

    SciTech Connect

    Lee, Jong Hoon; Kim, Dae Yong; Nam, Taek-Keun; Yoon, Sei-Chul; Lee, Doo Seok; Park, Ji Won; Oh, Jae Hwan; Chang, Hee Jin; Yoon, Mee Sun; Jeong, Jae-Uk; Jang, Hong Seok

    2012-11-15

    Purpose: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P = .045) and N (P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P = .025) and overall survival (P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and

  5. Neoadjuvant Therapy in Differentiated Thyroid Cancer

    PubMed Central

    Le, Valerie H.; Camille, Nadia; Miles, Brett A.; Teng, Marita S.; Genden, Eric M.; Misiukiewicz, Krzysztof J.

    2016-01-01

    Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC. PMID:27747102

  6. Principles of adoptive T cell cancer therapy

    PubMed Central

    June, Carl H.

    2007-01-01

    The transfusion of T cells, also called adoptive T cell therapy, is an effective treatment for viral infections and has induced regression of cancer in early-stage clinical trials. However, recent advances in cellular immunology and tumor biology are guiding new approaches to adoptive T cell therapy. For example, use of engineered T cells is being tested as a strategy to improve the functions of effector and memory T cells, and manipulation of the host to overcome immunotoxic effects in the tumor microenvironment has led to promising results in early-stage clinical trials. Challenges that face the field and must be addressed before adoptive T cell therapy can be translated into routine clinical practice are discussed. PMID:17476350

  7. Gastric cancer and trastuzumab: first biologic therapy in gastric cancer

    PubMed Central

    Gunturu, Krishna S.; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.

    2013-01-01

    Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer. PMID:23450234

  8. Advances in Neutron Capture Therapy

    SciTech Connect

    Soloway, A.H.; Barth, R.F.; Carpenter, D.E.

    1993-12-31

    This volume contains the proceedings of the Fifth International Symposium on Neutron Capture Therapy held September 14--17, 1992 in Columbus, Ohio. Individual papers were separately abstracted and indexed for the database.

  9. HIV gene therapy research advances.

    PubMed

    Jacobson, Jeffrey M

    2013-02-28

    In this issue of Blood, Tebas et al report antiviral effects in a clinical trial of multiple infusions of lentiviral vector–modified autologous CD4T lymphocytes in 17 HIV-infected patients aviremic on antiretroviral therapy (ART).

  10. Targeting the EGF Receptor for Ovarian Cancer Therapy

    PubMed Central

    Zeineldin, Reema; Muller, Carolyn Y.; Stack, M. Sharon; Hudson, Laurie G.

    2010-01-01

    Ovarian carcinoma is the leading cause of death from gynecologic malignancy in the US. Factors such as the molecular heterogeneity of ovarian tumors and frequent diagnosis at advanced stages hamper effective disease treatment. There is growing emphasis on the identification and development of targeted therapies to disrupt molecular pathways in cancer. The epidermal growth factor (EGF) receptor is one such protein target with potential utility in the management of ovarian cancer. This paper will discuss contributions of EGF receptor activation to ovarian cancer pathogenesis and the status of EGF receptor inhibitors and EGF receptor targeted therapies in ovarian cancer treatment. PMID:20066160

  11. Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

    SciTech Connect

    Kato, Shingo; Ohno, Tatsuya; Thephamongkhol, Kullathorn; Chansilpa, Yaowalak; Cao, Jianping; Xu, Xiaoting; Devi, C. R. Beena; Swee, Tang Tieng; Calaguas, Miriam J.C.; Reyes, Rey H. de los; Cho, Chul-Koo; Dung, To Anh; Supriana, Nana; Erawati, Dyah; Mizuno, Hideyuki; Nakano, Takashi; Tsujii, Hirohiko

    2013-09-01

    Purpose: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Methods and Materials: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m{sup 2}) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. Results: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. Conclusions: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.

  12. Making circadian cancer therapy practical.

    PubMed

    Block, Keith I; Block, Penny B; Fox, Susan Reynolds; Birris, Jamie Stouffer; Feng, April Y; de la Torre, Michael; Nathan, Deva; Tothy, Peter; Maki, Amanda K; Gyllenhaal, Charlotte

    2009-12-01

    Practical circadian therapy for the cancer patient involves 3 spheres of intervention-improving lifestyle, optimizing internal biochemical milieu, and adjusting treatment times. The potential value of improving overall circadian functioning is shown in the work of Mormont et al in which pronounced rest-activity rhythms were associated with better survival in colorectal cancer patients receiving chronomodulated chemotherapy. Lifestyle interventions that may improve circadian functioning involve diet, physical activity, and mind-body therapies. A diet that is anti-inflammatory and has appropriate carbohydrate intake, as well as regular meal timing, encourages normal circadian cycles. Adequate daytime physical activity encourages restful sleep, and morning light exposure during exercise may entrain melatonin rhythms. Meditation and other mind-body therapies can reduce anxiety and depression that may disrupt sleep. Aspects of the biochemical milieu that specifically disrupt circadian functioning are inflammation and stress hormones. Inflammation and cytokine disruption can be addressed with diet, herbs, and other natural substances. Chronomodulation of chemotherapy in a US clinical setting will be discussed. A series of 12 cases will be presented of patients who experienced grade 3 to 4 toxicities with various chemotherapy regimens for colorectal cancer. When rechallenged with the same regimens administered chronotherapeutically, none of the patients experienced grade 3 to 4 toxicity. Integrating all the above treatment modalities has the potential to improve both the quality of life and disease outcomes in cancer patients.

  13. Vectors for cancer gene therapy.

    PubMed

    Zhang, J; Russell, S J

    1996-09-01

    Many viral and non-viral vector systems have now been developed for gene therapy applications. In this article, the pros and cons of these vector systems are discussed in relation to the different cancer gene therapy strategies. The protocols used in cancer gene therapy can be broadly divided into six categories including gene transfer to explanted cells for use as cell-based cancer vaccines; gene transfer to a small number of tumour cells in situ to achieve a vaccine effect; gene transfer to vascular endothelial cells (VECs) lining the blood vessels of the tumour to interfere with tumour angiogenesis; gene transfer to T lymphocytes to enhance their antitumour effector capability; gene transfer to haemopoietic stem cells (HSCs) to enhance their resistance to cytotoxic drugs and gene transfer to a large number of tumour cells in situ to achieve nonimmune tumour reduction with or without bystander effect. Each of the six strategies makes unique demands on the vector system and these are discussed with reference to currently available vectors. Aspects of vector biology that are in need of further development are discussed in some detail. The final section points to the potential use of replicating viruses as delivery vehicles for efficient in vivo gene transfer to disseminated cancers.

  14. Evolving Approaches to Patients with Advanced Differentiated Thyroid Cancer

    PubMed Central

    Sherman, Steven I.

    2013-01-01

    Advanced differentiated thyroid cancer (DTC), defined by clinical characteristics including gross extrathyroidal invasion, distant metastases, radioiodine (RAI) resistance, and avidity for 18-fluorodeoxyglucose (positron emission tomography-positive), is found in approximately 10–20% of patients with DTC. Standard therapy (surgery, RAI, TSH suppression with levothyroxine) is ineffective for many of these patients, as is standard chemotherapy. Our understanding of the molecular mechanisms leading to DTC and the transformation to advanced DTC has rapidly evolved over the past 15–20 years. Newer targeted therapy, specifically inhibitors of intracellular kinase signaling pathways, and cooperative multicenter clinical trials have dramatically changed the therapeutic landscape for patients with advanced DTC. In this review focusing on morbidities, molecules, and medicinals, we present a patient with advanced DTC, explore the genetics and molecular biology of advanced DTC, and review evolving therapies for these patients including multikinase inhibitors, selective kinase inhibitors, and combination therapies. PMID:23575762

  15. Molecular profiling of a case of advanced pancreatic cancer identifies an active and tolerable combination of targeted therapy with backbone chemotherapy

    PubMed Central

    Vanderwalde, Ari; Javadi, Nader; Feldman, Rebecca; Reddy, Sandeep Bobby

    2016-01-01

    Typical survival with common 1st-line regimens for pancreatic cancer range from 6-11 months. We report a case of a patient with stage IVB pancreatic adenocarcinoma treated with gemcitabine and erlotinib who stopped therapy after 3 months without achieving a response due to intolerance. To decide upon additional treatment options, molecular analysis was performed on liver metastasis which revealed KRAS, FBXW7, APC, and ATM mutations, with thymidylate synthase (TS) negativity and PD-1 positivity. Based on this profile of TS negativity and ATM mutation, a combination strategy was devised consisting of capecitabine, oxaliplatin, bevacizumab and vorinostat. The patient had a near complete response to therapy with this regimen. In refractory metastatic pancreatic cancer, responses of this magnitude are rarely seen. To our knowledge, this represents the first demonstrated activity of this combination in the metastatic setting which could prompt further investigation of its use in large scale clinical trials. PMID:27034805

  16. Can advanced-stage ovarian cancer be cured?

    PubMed

    Narod, Steven

    2016-04-01

    Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer. PMID:26787282

  17. Engineering antibodies for cancer therapy.

    PubMed

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  18. Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies

    PubMed Central

    Luis, Michael; Tavares, Ana; Carvalho, Liliana S; Lara-Santos, Lúcio; Araújo, António; de Mello, Ramon Andrade

    2013-01-01

    Globally, gastric cancer is the 4th most frequently diagnosed cancer and the 2nd leading cause of death from cancer, with an estimated 990000 new cases and 738000 deaths registered in 2008. In the advanced setting, standard chemotherapies protocols acquired an important role since last decades in prolong survival. Moreover, recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER2) therapies. Trastuzumab, an anti-HER2 monoclonal antibody, was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy. Further, HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field. Thus, we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer, providing a comprehensive overview of molecular mechanisms and novel trials involved. PMID:24151357

  19. Endoscopic photodynamic therapy (PDT) for oesophageal cancer.

    PubMed

    Moghissi, Keyvan

    2006-06-01

    Endoscopic photodynamic therapy (PDT) is undertaken only when tumour is visible endoscopically with malignancy biopsy confirmed. Patients will be either Group A: inoperable cases with locally advanced cancer when the aim is palliation of dysphagia, or Group E: patients with early stage I-II disease who are unsuitable for surgery or decline operation, when the intent is curative. Following assessment for suitability for PDT and counselling, Photofrin 2mg/(kgbw) is administered 24-72h before endoscopic illumination using a Diode 630nm laser. Illumination may be either interstitial or intraluminal at a dose of 100-200J/cm. PMID:25049097

  20. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Hong, Theodore S.; Moughan, Jennifer; Garofalo, Michael C.; Bendell, Johanna; Berger, Adam C.; Oldenburg, Nicklas B.E.; Anne, Pramila Rani; Perera, Francisco; Jabbour, Salma K.; Nowlan, Adam; DeNittis, Albert; Crane, Christopher

    2015-09-01

    Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

  1. Antiangiogenic Steroids in Human Cancer Therapy.

    PubMed

    Pietras, Richard J; Weinberg, Olga K

    2005-03-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na(+)/H(+) exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell-cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies, including ovarian, non

  2. Gene Therapy for Lung Cancer.

    PubMed

    Lara-Guerra, Humberto; Roth, Jack A

    2016-01-01

    Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein. PMID:27481008

  3. Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2016-06-27

    Adenocarcinoma of the Gastroesophageal Junction; Gastric Cardia Adenocarcinoma; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer

  4. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer: Retrospective cohort study, 7-year experience with 247 patients at the National Cancer Center in China.

    PubMed

    Chen, Yingtai; Che, Xu; Zhang, Jianwei; Huang, Huang; Zhao, Dongbing; Tian, Yantao; Li, Yexiong; Feng, Qinfu; Zhang, Zhihui; Jiang, Qinglong; Zhang, Shuisheng; Tang, Xiaolong; Huang, Xianghui; Chu, Yunmian; Zhang, Jianghu; Sun, Yuemin; Zhang, Yawei; Wang, Chengfeng

    2016-09-01

    To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT.A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center.Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47-0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32-0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04-0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment.Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID:27661028

  5. SU-E-J-244: Development and Validation of a Knowledge Based Planning Model for External Beam Radiation Therapy of Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Liu, Z; Kennedy, A; Larsen, E; Hayes, C; Grow, A; Bahamondes, S.; Zheng, Y; Wu, X; Choi, M; Pai, S; Li, J; Cranford, K

    2015-06-15

    Purpose: The study aims to develop and validate a knowledge based planning (KBP) model for external beam radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). Methods: RapidPlan™ technology was used to develop a lung KBP model. Plans from 65 patients with LA-NSCLC were used to train the model. 25 patients were treated with VMAT, and the other patients were treated with IMRT. Organs-at-risk (OARs) included right lung, left lung, heart, esophagus, and spinal cord. DVH and geometric distribution DVH were extracted from the treated plans. The model was trained using principal component analysis and step-wise multiple regression. Box plot and regression plot tools were used to identify geometric outliers and dosimetry outliers and help fine-tune the model. The validation was performed by (a) comparing predicted DVH boundaries to actual DVHs of 63 patients and (b) using an independent set of treatment planning data. Results: 63 out of 65 plans were included in the final KBP model with PTV volume ranging from 102.5cc to 1450.2cc. Total treatment dose prescription varied from 50Gy to 70Gy based on institutional guidelines. One patient was excluded due to geometric outlier where 2.18cc of spinal cord was included in PTV. The other patient was excluded due to dosimetric outlier where the dose sparing to spinal cord was heavily enforced in the clinical plan. Target volume, OAR volume, OAR overlap volume percentage to target, and OAR out-of-field volume were included in the trained model. Lungs and heart had two principal component scores of GEDVH, whereas spinal cord and esophagus had three in the final model. Predicted DVH band (mean ±1 standard deviation) represented 66.2±3.6% of all DVHs. Conclusion: A KBP model was developed and validated for radiotherapy of LA-NSCLC in a commercial treatment planning system. The clinical implementation may improve the consistency of IMRT/VMAT planning.

  6. Photodynamic therapy of gastric cancer

    NASA Astrophysics Data System (ADS)

    Kharnas, Sergey S.; Kuzin, N. M.; Zavodnov, Victor Y.; Sclyanskaya, Olga A.; Linkov, Kirill G.; Loschenov, Victor B.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Stratonnikov, Alexander A.; Steiner, Rudolf W.

    1996-01-01

    Photodynamic therapy (PDT) with the use of laser endoscopic spectrum analyzer (LESA-5), the spectral-analyzing video-imaging system, Kr laser and various types of catheters for different tumor localizations, and Phthalocyanine aluminum photosensitizers in patients with gastric cancer was discussed. PDT was carried out in fifteen patients with gastric cancer. There were the following indications for PDT: early gastric cancer (3 patients), malignant stenosis of the cardia or pyloric portion of the stomach (4 patients), cancer of gastric stump with stenosis of gastrojejunal anastomosis (1 patient), preoperative treatment of patients with large but probably resectable gastric tumor size (7 patients). Usually we used 3 - 4 seances of laser treatment 10 - 30 minutes long. Concentration of photosensitizer in normal and malignant tissue was controlled by LESA-5. Treatment was monitored by spectral-analyzing video- imaging system in fluorescent light. The results show high efficiency of PDT especially in patients with early gastric cancer (necrosis of all tumor mass, i.e. complete regression of tumor). For all other patients we obtained partial regression of gastric cancer.

  7. Curcumin in combined cancer therapy.

    PubMed

    Troselj, Koraljka Gall; Kujundzic, Renata Novak

    2014-01-01

    The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma longa), influences a wide variety of cellular processes through the reshaping of many molecular targets. One of them, nuclear factor kappa B (NF-κB), represents a strong mediator of inflammation and, in a majority of systems, supports the pro-proliferative features of cancer cells. The application of various anticancer drugs, cytostatics, triggers signals which lead to an increase in cellular NF-κB activity. As a consequence, cancer cells often reshape their survival signaling pathways and, over time, become resistant to applied therapy. Curcumin was shown to be a strong inhibitor of NF-κB activity and its inhibitory effect on NF-κB related pathways often leads to cellular apoptotic response. All these facts, tested and confirmed in many different biological systems, have paved the way for research aimed to elucidate the potential beneficial effects of combining curcumin and various anti-cancer drugs in order to establish more efficient and less toxic cancer treatment modalities. This review addresses certain aspects of NF-κB-related inflammatory response, its role in carcinogenesis and therapy benefits that may be gained through silencing NF-κB by selectively combining curcumin and various anticancer drugs.

  8. The redox-active nanomaterial toolbox for cancer therapy.

    PubMed

    Ibañez, Irene L; Notcovich, Cintia; Catalano, Paolo N; Bellino, Martín G; Durán, Hebe

    2015-04-01

    Advances in nanomaterials science contributed in recent years to develop new devices and systems in the micro and nanoscale for improving the diagnosis and treatment of cancer. Substantial evidences associate cancer cells and tumor microenvironment with reactive oxygen species (ROS), while conventional cancer treatments and particularly radiotherapy, are often mediated by ROS increase. However, the poor selectivity and the toxicity of these therapies encourage researchers to focus efforts in order to enhance delivery and to decrease side effects. Thus, the development of redox-active nanomaterials is an interesting approach to improve selectivity and outcome of cancer treatments. Herein, we describe an overview of recent advances in redox nanomaterials in the context of current and emerging strategies for cancer therapy based on ROS modulation.

  9. The redox-active nanomaterial toolbox for cancer therapy.

    PubMed

    Ibañez, Irene L; Notcovich, Cintia; Catalano, Paolo N; Bellino, Martín G; Durán, Hebe

    2015-04-01

    Advances in nanomaterials science contributed in recent years to develop new devices and systems in the micro and nanoscale for improving the diagnosis and treatment of cancer. Substantial evidences associate cancer cells and tumor microenvironment with reactive oxygen species (ROS), while conventional cancer treatments and particularly radiotherapy, are often mediated by ROS increase. However, the poor selectivity and the toxicity of these therapies encourage researchers to focus efforts in order to enhance delivery and to decrease side effects. Thus, the development of redox-active nanomaterials is an interesting approach to improve selectivity and outcome of cancer treatments. Herein, we describe an overview of recent advances in redox nanomaterials in the context of current and emerging strategies for cancer therapy based on ROS modulation. PMID:25597786

  10. Salivary gland and associated complications in head and neck cancer therapy.

    PubMed

    Kumar, Satish; Ram, Saravanan; Navazesh, Mahvash

    2011-09-01

    Xerostomia and salivary gland hypofunction are two of the most common and significant complications of head and neck cancer therapy in the head and neck region. This article will provide a brief overview of salivary gland hypofunction and associated complications in head and neck cancer therapy, mainly in radiation therapy. The discussion will include quality of life issues as well as current advances in cancer therapy to reduce xerostomia and salivary gland hypofunction.

  11. Recent Advances in Combined Modality Therapy

    PubMed Central

    Nyati, Mukesh K.; Morgan, Meredith A.; Lawrence, Theodore S.

    2010-01-01

    Combined modality therapy emerged from preclinical data showing that carefully chosen drugs could enhance the sensitivity of tumor cells to radiation while having nonoverlapping toxicities. Recent advances in molecular biology involving the identification of cellular receptors, enzymes, and pathways involved in tumor growth and immortality have resulted in the development of biologically targeted drugs. This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy. PMID:20413642

  12. Cancer Therapy Evaluation Program | Office of Cancer Genomics

    Cancer.gov

    The Cancer Therapy Evaluation Program (CTEP) seeks to improve the lives of cancer patients by finding better treatments, control mechanisms, and cures for cancer. CTEP funds a national program of cancer research, sponsoring clinical trials to evaluate new anti-cancer agents.

  13. T Cell Receptor Gene Therapy for Cancer

    PubMed Central

    Schmitt, Thomas M.; Ragnarsson, Gunnar B.

    2009-01-01

    Abstract T cell-based adoptive immunotherapy has been shown to be a promising treatment for various types of cancer. However, adoptive T cell therapy currently requires the custom isolation and characterization of tumor-specific T cells from each patient—a process that can be not only difficult and time-consuming but also often fails to yield high-avidity T cells, which together have limited the broad application of this approach as a clinical treatment. Employing T cell receptor (TCR) gene therapy as a component of adoptive T cell therapy strategies can overcome many of these obstacles, allowing autologous T cells with a defined specificity to be generated in a much shorter time period. Initial studies using this approach have been hampered by a number of technical difficulties resulting in low TCR expression and acquisition of potentially problematic specificities due to mispairing of introduced TCR chains with endogenous TCR chains. The last several years have seen substantial progress in our understanding of the multiple facets of TCR gene therapy that will have to be properly orchestrated for this strategy to succeed. Here we outline the challenges of TCR gene therapy and the advances that have been made toward realizing the promise of this approach. PMID:19702439

  14. Radiation therapy for breast cancer: Literature review.

    PubMed

    Balaji, Karunakaran; Subramanian, Balaji; Yadav, Poonam; Anu Radha, Chandrasekaran; Ramasubramanian, Velayudham

    2016-01-01

    Concave shape with variable size target volume makes treatment planning for the breast/chest wall a challenge. Conventional techniques used for the breast/chest wall cancer treatment provided better sparing of organs at risk (OARs), with poor conformity and uniformity to the target volume. Advanced technologies such as intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) improve the target coverage at the cost of higher low dose volumes to OARs. Novel hybrid techniques present promising results in breast/chest wall irradiation in terms of target coverage as well as OARs sparing. Several published data compared these technologies for the benefit of the breast/chest wall with or without nodal volumes. The aim of this article is to review relevant data and identify the scope for further research in developing optimal treatment plan for breast/chest wall cancer treatment. PMID:27545009

  15. Radiation therapy for breast cancer: Literature review.

    PubMed

    Balaji, Karunakaran; Subramanian, Balaji; Yadav, Poonam; Anu Radha, Chandrasekaran; Ramasubramanian, Velayudham

    2016-01-01

    Concave shape with variable size target volume makes treatment planning for the breast/chest wall a challenge. Conventional techniques used for the breast/chest wall cancer treatment provided better sparing of organs at risk (OARs), with poor conformity and uniformity to the target volume. Advanced technologies such as intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) improve the target coverage at the cost of higher low dose volumes to OARs. Novel hybrid techniques present promising results in breast/chest wall irradiation in terms of target coverage as well as OARs sparing. Several published data compared these technologies for the benefit of the breast/chest wall with or without nodal volumes. The aim of this article is to review relevant data and identify the scope for further research in developing optimal treatment plan for breast/chest wall cancer treatment.

  16. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.

    PubMed

    Bramhall, S R; Schulz, J; Nemunaitis, J; Brown, P D; Baillet, M; Buckels, J A C

    2002-07-15

    Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified. PMID

  17. Imaging techniques for prostate cancer: implications for focal therapy

    PubMed Central

    Turkbey, Baris; Pinto, Peter A.; Choyke, Peter L.

    2012-01-01

    The multifocal nature of prostate cancer has necessitated whole-gland therapy in the past; however, since the widespread use of PSA screening, patients frequently present with less-advanced disease. Many men with localized disease wish to avoid the adverse effects of whole-gland therapy; therefore, focal therapy for prostate cancer is being considered as a treatment option. For focal treatment to be viable, accurate imaging is required for diagnosis, staging, and monitoring of treatment. Developments in MRI and PET have brought more attention to prostate imaging and the possibility of improving the accuracy of focal therapy. In this Review, we discuss the advantages and disadvantages of conventional methods for imaging the prostate, new developments for targeted imaging, and the possible role of image-guided biopsy and therapy for localized prostate cancer. PMID:19352394

  18. Precision Therapy for Lung Cancer: Tyrosine Kinase Inhibitors and Beyond.

    PubMed

    Rajan, Arun; Schrump, David S

    2015-01-01

    For patients with advanced cancers there has been a concerted effort to transition from a generic treatment paradigm to one based on tumor-specific biologic, and patient-specific clinical characteristics. This approach, known as precision therapy has been made possible owing to widespread availability and a reduction in the cost of cutting-edge technologies that are used to study the genomic, proteomic, and metabolic attributes of individual tumors. This review traces the evolution of precision therapy for lung cancer from the identification of molecular subsets of the disease to the development and approval of tyrosine kinase, as well as immune checkpoint inhibitors for lung cancer therapy. Challenges of the precision therapy era including the emergence of acquired resistance, identification of untargetable mutations, and the effect on clinical trial design are discussed. We conclude by highlighting newer applications for the concept of precision therapy. PMID:26074108

  19. Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

    PubMed Central

    Mavroudi, Maria; Zarogoulidis, Paul; Porpodis, Konstantinos; Kioumis, Ioannis; Lampaki, Sofia; Yarmus, Lonny; Malecki, Raf; Zarogoulidis, Konstantinos; Malecki, Marek

    2014-01-01

    Introduction Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The statistics speak for themselves with the grim reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem cells’ guided gene therapy. Review of therapeutic strategies in preclinical and clinical trials Stem cells have the unique potential for self renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells only. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for

  20. [A Case of Luminal-HER2 Advanced Breast Cancer with Liver Metastasis Showed Pathological Complete Response to the Therapy with Pertuzumab plus Trastuzumab plus Docetaxel].

    PubMed

    Hamaoka, Asako; Matsuda, Takayuki; Konishi, Eiichi; Taguchi, Tetsuya

    2016-09-01

    A 56-year-old woman noticed a mass on her left breast and visited our hospital. An irregular mass of 3 cm with associated axillary lymphadenopathy was detected under the nipple of the left breast. After further evaluations, the diagnosis was an invasive ductal carcinoma(scirrhous carcinoma)ofLuminal -HER2 type with liver metastases(cT4bN1M1, Stage IV). Treatment was initiated with a combination ofpertuzumab, trastuzumab, and docetaxel(PTD). The primary tumor showed a clinical complete response, and the liver metastases and the axillary lymph node metastases showed a partial response. Docetaxel was excluded after the 8th cycle because the patient experienced severe edema. After 15 cycles of therapy, the primary tumor was resected, and pathological examination revealed a pathological complete response ofthe primary lesion. Thus, PTD combination therapy is effective for Stage IV metastatic breast cancer ofthe Luminal-HER2 type. PMID:27628551

  1. Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

    PubMed

    Witherby, Sabrina; Rizack, Tina; Sakr, Bachir J; Legare, Robert D; Sikov, William M

    2016-01-01

    Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

  2. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  3. Advances in stem cell therapy.

    PubMed

    Pérez López, Silvia; Otero Hernández, Jesús

    2012-01-01

    Since the beginning of stem cell biology, considerable effort has been focused in the translation of scientific insights into new therapies. Cell-based assays represent a new strategy for organ and tissue repair in several pathologies. Moreover, alternative treatment strategies are urgently needed due to donor organ shortage that costs many lives every year and results in lifelong immunosuppression. At the moment, only the use of hematopoietic stem cells is considered as the standard for the treatment of malignant and genetic bone marrow disorders, being all other stem cell applications highly experimental. The present chapter tries to summarize some ongoing approaches of stem cell regenerative medicine and also introduces recent findings from published studies and trials conducted in various tissues such as skeletal muscle, liver and lung.

  4. The Long-HER Study: Clinical and Molecular Analysis of Patients with HER2+ Advanced Breast Cancer Who Become Long-Term Survivors with Trastuzumab-Based Therapy

    PubMed Central

    Gámez-Pozo, Angelo; Pérez Carrión, Ramón M.; Manso, Luis; Crespo, Carmen; Mendiola, Cesar; López-Vacas, Rocío; Berges-Soria, Julia; López, Isabel Álvarez; Margeli, Mireia; Calero, Juan L. Bayo; Farre, Xavier González; Santaballa, Ana; Ciruelos, Eva M.; Afonso, Ruth; Lao, Juan; Catalán, Gustavo; Gallego, José V. Álvarez; López, José Miramón; Bofill, Francisco J. Salvador; Borrego, Manuel Ruiz; Espinosa, Enrique; Vara, Juan A. Fresno; Zamora, Pilar

    2014-01-01

    Background Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment. Methods Data were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples. Results 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. Conclusions Trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a

  5. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  6. Pancreatic Cancer: Progress in Systemic Therapy

    PubMed Central

    Perkhofer, Lukas; Ettrich, Thomas J.; Seufferlein, Thomas

    2014-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths in the Western world. Due to lack of specific symptoms and no accessible precursor lesions, primary diagnosis is commonly delayed, resulting in the identification of only 15-20% of patients with potentially curable disease. The major limiting factor is an already locally advanced or metastatic disease at the time of diagnosis. Consequently, systemic therapy forms the backbone of treatment strategy for the majority of patients. Summary A deeper understanding of the molecular characteristics of pancreatic cancer has led to the identification of several potential therapeutic targets. A variety of targeted therapies are currently under clinical evaluation as single agents or in combination with chemotherapy for PDAC. This review highlights the current state of chemotherapy in pancreatic cancer and provides an outlook on its future perspectives. Key Message This review focuses on the current chemotherapy regimens for the systemic treatment of PDAC. Practical Implications Various neoadjuvant approaches have been explored, including chemoradiation, chemotherapy followed by chemoradiation or intensified chemotherapy without defining a standard of care so far. The standard of care is gemcitabine or 5-fluorouracil. The oral fluoropyrimidine S-1 may be a promising new agent in this setting. For first-line treatment of metastatic pancreatic cancer, no targeted therapy has yet demonstrated clinical benefit apart from the combination of the tyrosine kinase inhibitor erlotinib plus gemcitabine. Recently, novel chemotherapeutic regimens such as FOLFIRINOX and gemcitabine plus nanoparticle albumin-bound paclitaxel have been introduced. Both combinations have proved to be superior to the standard gemcitabine regimen. For second-line treatment the combination of 5-fluorouracil/leucovorin and oxaliplatin yields improved results compared to best supportive care. PMID:26672477

  7. Chemotherapy for Advanced Non-small Cell Lung Cancer.

    PubMed

    Dietrich, Martin F; Gerber, David E

    2016-01-01

    Non-small cell lung cancer has seen an unprecedented augmentation of therapeutic options over the last couple of years. Improved understanding of molecular drivers and the role of the immune system in cancer therapy have brought new drugs to the armamentarium. Despite these advances, cytotoxic chemotherapy remains a substantial part of therapy for most patients in locally advanced and metastatic stage. Initially thought to be a chemotherapy-resistant entity, meta-analyses in the mid-1990s demonstrated modest efficacy of platinum-based therapy. Further combination trials demonstrated enhanced efficacy for several regimen in first and second lines, including the introduction of antimetabolites, taxanes, and anti-angiogenic agents. Maintenance chemotherapy has been another novel, successful approach for management of metastatic disease. Herein, we summarize the current concepts of chemotherapy, its applicability to the different histologies, and novel concepts of therapy. PMID:27535392

  8. Genetically Engineered Immunotherapy for Advanced Cancer

    Cancer.gov

    In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer

  9. Types of Cancer Treatment: Hormone Therapy

    Cancer.gov

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  10. Bile Duct (Cholangiocarcinoma) Cancer: Radiation Therapy

    MedlinePlus

    ... form of radiation for bile duct cancer. External beam radiation therapy (EBRT) This type of radiation therapy ... determine the correct angles for aiming the radiation beams and the proper dose of radiation. The treatment ...

  11. Extended Adjuvant Therapy for Breast Cancer

    Cancer.gov

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  12. Combination Therapy for Advanced Kaposi Sarcoma

    Cancer.gov

    In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

  13. Advances in cancer pain from bone metastasis

    PubMed Central

    Zhu, Xiao-Cui; Zhang, Jia-Li; Ge, Chen-Tao; Yu, Yuan-Yang; Wang, Pan; Yuan, Ti-Fei; Fu, Cai-Yun

    2015-01-01

    With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out how to improve the life quality of patients with cancer has become increasingly prominent. Pain, especially bone pain, is the most common symptom in malignancy patients, which seriously affects the life quality of patients with cancer. The research of cancer pain has a breakthrough due to the development of the animal models of cancer pain in recent years, such as the animal models of mouse femur, humerus, calcaneus, and rat tibia. The establishment of several kinds of animal models related to cancer pain provides a new platform in vivo to investigate the molecular mechanisms of cancer pain. In this review, we focus on the advances of cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the drug treatment of cancer pain in the animal models. PMID:26316696

  14. The influence of hormone therapies on colon and rectal cancer.

    PubMed

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels; Løkkegaard, Ellen; Kjær, Susanne Krüger

    2016-05-01

    Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0.83, 0.72-0.96 and 0.89, 0.80-1.00), compared to never users. Transdermal estrogen-only therapy implied more protection than oral administration, while no significant influence was found of regimen, progestin type, nor of tibolone. The benefit of HT was stronger for long-term hormone users; and hormone users were at lower risk of advanced stage of colorectal cancer, which seems supportive for a causal association between hormone therapy and colorectal cancer. PMID:26758900

  15. Molecular profiling of childhood cancer: Biomarkers and novel therapies

    PubMed Central

    Saletta, Federica; Wadham, Carol; Ziegler, David S.; Marshall, Glenn M.; Haber, Michelle; McCowage, Geoffrey; Norris, Murray D.; Byrne, Jennifer A.

    2014-01-01

    Background Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. Scope of review This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. Major conclusions There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. General significance The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations. PMID:26675306

  16. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials. What does statistical proof mean. How can we consider a quality of life endpoint in the adjuvant setting. Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine.

  17. Single-agent maintenance therapy for advanced non-small cell lung cancer (NSCLC): a systematic review and Bayesian network meta-analysis of 26 randomized controlled trials

    PubMed Central

    Zeng, Xiaoning; Ma, Yuan

    2016-01-01

    Background The benefit of maintenance therapy has been confirmed in patients with non-progressing non-small cell lung cancer (NSCLC) after first-line therapy by many trials and meta-analyses. However, since few head-to-head trials between different regimens have been reported, clinicians still have little guidance on how to select the most efficacious single-agent regimen. Hence, we present a network meta-analysis to assess the comparative treatment efficacy of several single-agent maintenance therapy regimens for stage III/IV NSCLC. Methods A comprehensive literature search of public databases and conference proceedings was performed. Randomized clinical trials (RCTs) meeting the eligible criteria were integrated into a Bayesian network meta-analysis. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). Results A total of 26 trials covering 7,839 patients were identified, of which 24 trials were included in the OS analysis, while 23 trials were included in the PFS analysis. Switch-racotumomab-alum vaccine and switch-pemetrexed were identified as the most efficacious regimens based on OS (HR, 0.64; 95% CrI, 0.45–0.92) and PFS (HR, 0.54; 95% CrI, 0.26–1.04) separately. According to the rank order based on OS, switch-racotumomab-alum vaccine had the highest probability as the most effective regimen (52%), while switch-pemetrexed ranked first (34%) based on PFS. Conclusions Several single-agent maintenance therapy regimens can prolong OS and PFS for stage III/IV NSCLC. Switch-racotumomab-alum vaccine maintenance therapy may be the most optimal regimen, but should be confirmed by additional evidence. PMID:27781159

  18. Emerging therapies in gastrointestinal cancers

    PubMed Central

    Nautiyal, Jyoti; Rishi, Arun K; Majumdar, Adhip PN

    2006-01-01

    Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancers. Therefore, interference with the activation of these growth factor receptors represents a promising strategy for development of novel and selective anticancer therapies. Indeed, a number of inhibitors that target either EGFR or HER-2, with the exception of a few that target both; have been developed for treatment of epithelial cancers. Since most solid tumors express different ErbB receptors and/or their ligands, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. Here we describe the significance of an ErbB family of receptors in epithelial cancers, and summarize different available therapeutics targeting these receptors. It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide variety of epithelial cancers. PMID:17167831

  19. Progress and controversies: Radiation therapy for prostate cancer.

    PubMed

    Martin, Neil E; D'Amico, Anthony V

    2014-01-01

    Radiation therapy remains a standard treatment option for men with localized prostate cancer. Alone or in combination with androgen-deprivation therapy, it represents a curative treatment and has been shown to prolong survival in selected populations. In this article, the authors review recent advances in prostate radiation-treatment techniques, photon versus proton radiation, modification of treatment fractionation, and brachytherapy-all focusing on disease control and the impact on morbidity. Also discussed are refinements in the risk stratification of men with prostate cancer and how these are better for matching patients to appropriate treatment, particularly around combined androgen-deprivation therapy. Many of these advances have cost and treatment burden implications, which have significant repercussions given the prevalence of prostate cancer. The discussion includes approaches to improve value and future directions for research. PMID:25234700

  20. Methionine enkephalin, its role in immunoregulation and cancer therapy.

    PubMed

    Zhao, Dingliang; Plotnikoff, Nicolas; Griffin, Noreen; Song, Tao; Shan, Fengping

    2016-08-01

    Methionine enkephalin (MENK), an endogenous neuropeptide has a crucial role in both neuroendocrine and immune systems. MENK is believed to have an immunoregulatory activity to have cancer biotherapy activity by binding to the opioid receptors on immune and cancer cells. Clinical trial studies in cancer patients have shown that MENK activates immune cells directly and by inhibiting regulatory T-cells (Tregs). MENK may also change the tumor microenvironment by binding to opioid receptor on or in cancer cells. All of these mechanisms of action have biologic significance and potential for use in cancer immunotherapy. Furthermore, they reveal a relationship between the endocrine and immune systems. Due to the apparent role of MENK in cancer therapy we reviewed herein, the research undertaken with MENK in recent years; which has advanced our understanding of the role MENK has in cancer progression and its relationship to immunity, supporting MENK as a new strategy for cancer immunotherapy.

  1. Major clinical research advances in gynecologic cancer in 2014.

    PubMed

    Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

    2015-04-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

  2. Endoluminal Therapy in Colorectal Cancer.

    PubMed

    Kelley, Katherine A; Tsikitis, V Liana

    2016-09-01

    Appropriate endoscopic resection for colorectal polyps can present a challenge to endoscopists, as these lesions may harbor malignancy. With recent advances in endoscopy, however, we are now entering an exciting frontier of endoscopic therapy for gastrointestinal lesions. These techniques include endoluminal mucosal resection and endoscopic submucosal dissection, which may be utilized on several colonic lesions. This article will discuss these principle endoscopic techniques, their outcomes, and briefly highlight their influence on endoscopic interventions, including transanal endoscopic microsurgery and natural orifice transluminal endoscopic surgery. PMID:27582646

  3. Clinical utility of ramucirumab in advanced gastric cancer.

    PubMed

    Chan, Matthew Mk; Sjoquist, Katrin M; Zalcberg, John R

    2015-01-01

    Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF) pathway including anti-VEGF antibody therapy (eg, bevacizumab), inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib), and inhibitors of vascular endothelial growth factor receptors (VEGFRs) (eg, ramucirumab). Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer.

  4. Bacterial proteins and peptides in cancer therapy

    PubMed Central

    Chakrabarty, Ananda M; Bernardes, Nuno; Fialho, Arsenio M

    2014-01-01

    Cancer is one of the most deadly diseases worldwide. In the last three decades many efforts have been made focused on understanding how cancer grows and responds to drugs. The dominant drug-development paradigm has been the “one drug, one target.” Based on that, the two main targeted therapies developed to combat cancer include the use of tyrosine kinase inhibitors and monoclonal antibodies. Development of drug resistance and side effects represent the major limiting factors for their use in cancer treatment. Nowadays, a new paradigm for cancer drug discovery is emerging wherein multi-targeted approaches gain ground in cancer therapy. Therefore, to overcome resistance to therapy, it is clear that a new generation of drugs is urgently needed. Here, regarding the concept of multi-targeted therapy, we discuss the challenges of using bacterial proteins and peptides as a new generation of effective anti-cancer drugs. PMID:24875003

  5. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  6. Percutaneous ablation therapies of inoperable pancreatic cancer: a systematic review

    PubMed Central

    Ierardi, Anna Maria; Lucchina, Natalie; Bacuzzi, Alessandro; Marco, De Chiara; Bracchi, Elena; Cocozza, Eugenio; Dionigi, Gianlorenzo; Tsetis, Dimitrios; Floridi, Chiara; Carrafiello, Gianpaolo

    2015-01-01

    Initial studies about ablation therapies of the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Development of techniques with high quality imaging used as guidance improve outcomes reducing complications. Moreover, only few experiences of percutaneous pancreatic ablations are reported. They are performed by very skilled operators in highly specialized centers. This review presents the current status of percutaneous local ablative therapies in the treatment of advanced pancreatic cancer. PMID:26424487

  7. Nanotechnology for breast cancer therapy.

    PubMed

    Tanaka, Takemi; Decuzzi, Paolo; Cristofanilli, Massimo; Sakamoto, Jason H; Tasciotti, Ennio; Robertson, Fredika M; Ferrari, Mauro

    2009-02-01

    Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of 'resistance' to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists-in the clinic, the pharmaceutical and the basic biological laboratory-and nanotechnologists-engineers, physicists, chemists and mathematicians-optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other 'environmental' divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may

  8. Image-guided focal therapy for prostate cancer

    PubMed Central

    Sankineni, Sandeep; Wood, Bradford J.; Rais-Bahrami, Soroush; Diaz, Annerleim Walton; Hoang, Anthony N.; Pinto, Peter A.; Choyke, Peter L.; Türkbey, Barış

    2014-01-01

    The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now starting to emerge—potentially achieving equivalent oncologic efficacy while avoiding the side effects of conventional radical surgery. The purpose of this article is to review the existing literature regarding the basis of various focal therapy techniques such as cryotherapy, microwave, laser, and high intensity focused ultrasound, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer. PMID:25205025

  9. Radiation therapy of esophageal cancer

    SciTech Connect

    Hancock, S.L.; Glatstein, E.

    1984-06-01

    Radiation therapy has been used extensively in the management of patients with cancer of the esophagus. It has demonstrated an ability to cure a small minority of patients. Cure is likely to be limited to patients who have lesions less than 5 cm in length and have minimal, if any, involvement of lymph nodes. Esophagectomy is likely to cure a similar, small percentage of patients with the same presentation of minimal disease but has a substantial acute postoperative mortality rate and greater morbidity than irradiation. Combining surgery and either preoperative or postoperative irradiation may cure a small percentage of patients beyond the number cured with either modality alone. Radiation has demonstrated benefit as an adjuvant to surgery following the resection of minimal disease. However, radiation alone has never been compared directly with surgery for the highly select, minimal lesions managed by surgery. Radiation provides good palliation of dysphagia in the majority of patients, and roughly one third may have adequate swallowing for the duration of their illness when ''radical'' doses have been employed. Surgical bypass procedures have greater acute morbidity but appear to provide more reliable, prolonged palliation of dysphagia. Several approaches to improving the efficacy of irradiation are currently under investigation. These approahces include fractionation schedules, radiosensitizers, neutron-beam therapy, and helium-ion therapy.

  10. Recent advances in the rational design of silica-based nanoparticles for gene therapy.

    PubMed

    Niut, Yuting; Popatt, Amirali; Yu, Meihua; Karmakar, Surajit; Gu, Wenyi; Yu, Chengzhong

    2012-10-01

    Gene therapy has attracted much attention in modern society and provides a promising approach for treating genetic disorders, diseases and cancers. Safe and effective vectors are vital tools to deliver genetic molecules to cells. This review summarizes recent advances in the rational design of silica-based nanoparticles and their applications in gene therapy. An overview of different types of genetic agents available for gene therapy is provided. The engineering of various silica nanoparticles is described, which can be used as versatile complexation tools for genetic agents and advanced gene therapy. Several challenges are raised and future research directions in the area of gene therapy using silica-based nanoparticles are proposed.

  11. Oncolytic virus therapy for cancer.

    PubMed

    Goldufsky, Joe; Sivendran, Shanthi; Harcharik, Sara; Pan, Michael; Bernardo, Sebastian; Stern, Richard H; Friedlander, Philip; Ruby, Carl E; Saenger, Yvonne; Kaufman, Howard L

    2013-01-01

    The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers.

  12. Oncolytic virus therapy for cancer

    PubMed Central

    Goldufsky, Joe; Sivendran, Shanthi; Harcharik, Sara; Pan, Michael; Bernardo, Sebastian; Stern, Richard H; Friedlander, Philip; Ruby, Carl E; Saenger, Yvonne; Kaufman, Howard L

    2013-01-01

    The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers. PMID:27512656

  13. Oxaliplatin, Fluorouracil, Erlotinib Hydrochloride, and Radiation Therapy Before Surgery and Erlotinib Hydrochloride After Surgery in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

    ClinicalTrials.gov

    2015-07-27

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage II Esophageal Cancer; Stage II Gastric Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer

  14. Systemic Therapy for Advanced Soft Tissue Sarcoma.

    PubMed

    Sheng, Jennifer Y; Movva, Sujana

    2016-10-01

    Soft tissue sarcomas are rare tumors that present with distant metastasis in up to 10% of patients. Survival has improved significantly because of advancements in histologic classification and improved management approaches. Older agents such as doxorubicin, ifosfamide, gemcitabine, and paclitaxel continue to demonstrate objective response rates from 18% to 25%. Newer agents such as trabectedin, eribulin, aldoxorubicin, and olaratumab have demonstrated improvements in progression-free survival, overall survival, or toxicity profiles. Future studies on treatment of advanced soft tissue sarcoma will continue to concentrate on reducing toxicity, personalization of therapy, and targeting novel pathways. PMID:27542647

  15. Virotherapy: cancer gene therapy at last?

    PubMed Central

    Bilsland, Alan E.; Spiliopoulou, Pavlina; Evans, T. R. Jeffry

    2016-01-01

    For decades, effective cancer gene therapy has been a tantalising prospect; for a therapeutic modality potentially able to elicit highly effective and selective responses, definitive efficacy outcomes have often seemed out of reach. However, steady progress in vector development and accumulated experience from previous clinical studies has finally led the field to its first licensed therapy. Following a pivotal phase III trial, Imlygic (talimogene laherparepvec/T-Vec) received US approval as a treatment for cutaneous and subcutaneous melanoma in October 2015, followed several weeks later by its European authorisation. These represent the first approvals for an oncolytic virotherapy. Imlygic is an advanced-generation herpesvirus-based vector optimised for oncolytic and immunomodulatory activities. Many other oncolytic agents currently remain in development, providing hope that current success will be followed by other diverse vectors that may ultimately come to constitute a new class of clinical anti-cancer agents. In this review, we discuss some of the key oncolytic viral agents developed in the adenovirus and herpesvirus classes, and the prospects for further enhancing their efficacy by combining them with novel immunotherapeutic approaches. PMID:27635234

  16. Virotherapy: cancer gene therapy at last?

    PubMed Central

    Bilsland, Alan E.; Spiliopoulou, Pavlina; Evans, T. R. Jeffry

    2016-01-01

    For decades, effective cancer gene therapy has been a tantalising prospect; for a therapeutic modality potentially able to elicit highly effective and selective responses, definitive efficacy outcomes have often seemed out of reach. However, steady progress in vector development and accumulated experience from previous clinical studies has finally led the field to its first licensed therapy. Following a pivotal phase III trial, Imlygic (talimogene laherparepvec/T-Vec) received US approval as a treatment for cutaneous and subcutaneous melanoma in October 2015, followed several weeks later by its European authorisation. These represent the first approvals for an oncolytic virotherapy. Imlygic is an advanced-generation herpesvirus-based vector optimised for oncolytic and immunomodulatory activities. Many other oncolytic agents currently remain in development, providing hope that current success will be followed by other diverse vectors that may ultimately come to constitute a new class of clinical anti-cancer agents. In this review, we discuss some of the key oncolytic viral agents developed in the adenovirus and herpesvirus classes, and the prospects for further enhancing their efficacy by combining them with novel immunotherapeutic approaches.

  17. Targeted therapy using nanotechnology: focus on cancer

    PubMed Central

    Sanna, Vanna; Pala, Nicolino; Sechi, Mario

    2014-01-01

    Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication. PMID:24531078

  18. Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain.

    PubMed

    Banz, Kurt; Bischoff, Helge; Brunner, Matthias; Chouaid, Christos; de Castro Carpeño, Javier; de Marinis, Filippo; Grossi, Francesco; Vergnenègre, Alain; Walzer, Stefan

    2011-12-01

    Objective of this indirect economic comparison was to estimate and compare management costs of grade 3/4 adverse events (AEs) reported for first-line erlotinib or pemetrexed maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC). The economic analysis was performed for Germany, France, Italy and Spain. Types and incidences of reported grade 3/4 AEs observed with erlotinib or pemetrexed maintenance therapy were retrieved from two recently published placebo-controlled trials. Country-specific estimates on standard treatment algorithms and incremental medical resource utilization associated with each of the reported grade 3/4 AEs have been obtained from clinical oncologists practicing in the four countries and co-authoring this article. The resource use items were subsequently assigned country-specific tariffs to estimate total per-patients costs associated with the AE profiles of the two compared maintenance regimens. For the economic analysis a customized economic spreadsheet model was employed. Our comparison shows lower total average per-patient AE management costs for erlotinib than for pemetrexed maintenance therapy in all four studied countries. Total estimated cost savings per patient in favour of erlotinib amount to € 121, € 237, € 106, and € 119 for Germany, France, Italy and Spain, respectively. These AE cost savings for erlotinib when compared to pemetrexed represent a decrease by 80%, 71%, 94%, and 82%, respectively. The study also discovered considerable differences in AE management costs across countries which are primarily due to differences in clinician's estimates of hospitalization referral rates. Erlotinib maintenance therapy in patients with advanced NSCLC causes lower AE management costs than pemetrexed maintenance therapy indicating a potentially superior tolerability profile. PMID:21592611

  19. Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial

    PubMed Central

    Brundage, Michael; Sydes, Matthew R.; Parulekar, Wendy R.; Warde, Padraig; Cowan, Richard; Bezjak, Andrea; Kirkbride, Peter; Parliament, Matthew; Moynihan, Clare; Bahary, Jean-Paul; Parmar, Mahesh K.B.; Sanders, Karen; Chen, Bingshu E.; Mason, Malcolm D.

    2015-01-01

    Purpose The NCIC CTG PR3/MRC PR07 randomized phase III trial compared androgen-deprivation therapy (ADT) alone versus ADT with radiotherapy (RT) for patients with locally advanced prostate cancer. This article reports the health-related quality-of-life (HRQOL) outcomes of this trial. Patients and Methods A total of 1,205 patients were randomly allocated to either ADT alone or ADT with RT. HRQOL was assessed at baseline and every 6 months thereafter using the European Organisation for Research and Treatment of Cancer Core Questionnaire and a prostate cancer–specific checklist or the Functional Assessment of Cancer Therapy–Prostate questionnaire. Mean changes from baseline scores for five function domains and nine symptom domains were analyzed as those most relevant to ADT and RT. The proportions of patients with improved, stable, or worsened HRQOL scores according to instrument-specific minimal important differences were calculated. Results Baseline questionnaires were completed by 1,028 patients (88%). At 6 months, RT had a statistically significant impact on mean score for bowel symptoms (P = .02), diarrhea (P < .001), urinary function (P = .003), and erectile dysfunction (P = .008); by 3 years, however, there were no significant between-group differences in any domain. Generalized linear mixed modeling revealed no significant between-arm differences in any of the function scales but showed significant deterioration in both arms over time for Functional Assessment of Cancer Therapy–Prostate total score, treatment outcome index, and physical and functional well-being. Conclusion The addition of RT to ADT for patients with locally advanced prostate cancer significantly improved overall survival and had only modest and transient negative impact on relevant domains of HRQOL. PMID:26014295

  20. Assessing the Role of Volumetric Modulated Arc Therapy (VMAT) Relative to IMRT and Helical Tomotherapy in the Management of Localized, Locally Advanced, and Post-Operative Prostate Cancer

    SciTech Connect

    Davidson, Melanie T.M.; Blake, Samuel J.; Batchelar, Deidre L.; Cheung, Patrick; Mah, Katherine

    2011-08-01

    Purpose: To quantify differences in treatment delivery efficiency and dosimetry between step-and-shoot intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) for prostate treatment. Methods and Materials: Twenty-five prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated for: prostate alone (n = 5), prostate + seminal vesicles (n = 5), prostate + seminal vesicles + pelvic lymph nodes (n = 5), prostate bed (n = 5), and prostate bed + pelvic lymph nodes (n = 5). Target coverage, dose homogeneity, integral dose, monitor units (MU), and sparing of organs at risk (OAR) were compared across techniques. Time required to deliver each plan was measured. Results: The dosimetric quality of IMRT, VMAT, and HT plans were comparable for target coverage (planning target volume V95%, clinical target volume V100% all >98.7%) and sparing of organs at risk (OAR) for all treatment groups. Although HT resulted in a slightly higher integral dose and mean doses to the OAR, it yielded a lower maximum dose to all OAR examined. VMAT resulted in reductions in treatment times over IMRT (mean = 75%) and HT (mean = 70%). VMAT required 15-38% fewer monitor units than IMRT over all treatment volumes, with the reduction per fraction ranging from 100-423 MU from the smallest to largest volumes. Conclusions: VMAT improves efficiency of delivery for equivalent dosimetric quality as IMRT and HT across various prostate cancer treatment volumes in the intact and postoperative settings.

  1. Current and emerging therapies in unresectable and recurrent gastric cancer

    PubMed Central

    Jou, Erin; Rajdev, Lakshmi

    2016-01-01

    Gastric cancer is one of the most lethal cancers worldwide despite many advances and options in therapy. As it is often diagnosed at an advanced stage, prognosis is poor with a median overall survival of less than twelve months. Chemotherapy remains the mainstay of treatment for these patients but it confers only a moderate survival advantage. There remains a need for new targeted treatment options and a way to better define patient populations who will benefit from these agents. In the past few years, there has been a better understanding of the biology, molecular profiling, and heterogeneity of gastric cancer. Our increased knowledge has led to the identification of gastric cancer subtypes and to the development of new targeted therapeutic agents. There are now two new targeted agents, trastuzumab and ramucirumab, that have recently been approved for the treatment of advanced and metastatic gastric cancer. There are also many other actively investigated targets, including epidermal growth factor receptor, the phosphatadylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, c-Met, poly ADP-ribose polymerase, and immune checkpoint inhibition. In this review, we discuss the current management of advanced gastric cancer as well as emerging targeted therapies and immunotherapy. PMID:27239108

  2. Photodynamic therapy (PDT) for lung cancer

    NASA Astrophysics Data System (ADS)

    Moghissi, K.; Dixon, Kate

    2005-11-01

    The Yorkshire Laser Centre has been engaged in Photodynamic Therapy (PDT) since 1990. In this article we present our experience highlighting the lesson learnt. 280 bronchoscopic PDT treatments have been carried out in 160 patients divided in 2 groups. Group A: (Nr 144) with advanced inoperable disease and Group E (Nr 16) with early stage cancer. PDT method was intravenous administration of 2mg/kg bw of Photofrin followed by bronchoscopic illumination of 630nm laser light. There was no procedure-related mortality. A total of 9 cases of photosensitivity (skin burn) occurred in the series (5.6% of patients). Every patient in both groups expressed their total satisfaction to treatment. Group A: Symptom relief was achieved in all. This was matched by improvement in significant bronchial opening (58.1%). Survival was 9.6 months (mean).This was greater in patients with better performance status and lower stage of disease. Group E: Every patient had a complete response to treatment. Survival in this group was 75.4 months (mean). We conclude that bronchoscopic PDT is indicated in both advanced and early stage lung cancer. In the former it provides symptomatic relief in all and survival benefit in some; in the latter it achieves long survival and potential cure.

  3. Advancing breast cancer survivorship among African-American women.

    PubMed

    Coughlin, Steven S; Yoo, Wonsuk; Whitehead, Mary S; Smith, Selina A

    2015-09-01

    Advances have occurred in breast cancer survivorship but, for many African-American women, challenges and gaps in relevant information remain. This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African-American women. For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African-American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African-American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. There is a need for a better understanding of breast cancer survivorship among African-American women. Additional evaluations of interventions for improving the quality of life and survival of African-American breast cancer survivors are desirable. PMID:26303657

  4. Complementary therapies for cancer-related symptoms.

    PubMed

    Deng, Gary; Cassileth, Barrie R; Yeung, K Simon

    2004-01-01

    Relief of cancer-related symptoms is essential in the supportive and palliative care of cancer patients. Complementary therapies such as acupuncture, mind-body techniques, and massage therapy can help when conventional treatment does not bring satisfactory relief or causes undesirable side effects. Controlled clinical trials show that acupuncture and hypnotherapy can reduce pain and nausea. Meditation, relaxation therapy, music therapy, and massage mitigate anxiety and distress. Pilot studies suggest that complementary therapies may treat xerostomia, hot flashes, and fatigue. Botanicals or dietary supplements are popular but often problematic. Concurrent use of herbal products with mainstream medical treatment should be discouraged.

  5. Antivascular Therapy for Epithelial Ovarian Cancer

    PubMed Central

    Duhoux, Francois P.; Machiels, Jean-Pascal

    2010-01-01

    Ovarian cancer is the fifth largest cancer killer in women. Improved understanding of the molecular pathways implicated in the pathogenesis of ovarian cancer has led to the investigation of novel targeted therapies. Ovarian cancer is characterized by an imbalance between pro- and antiangiogenic factors in favor of angiogenesis activation. Various antivascular strategies are currently under investigation in ovarian cancer. They can schematically be divided into antiangiogenic and vascular-disrupting therapies. This paper provides a comprehensive review of these new treatments targeting the tumor vasculature in this disease. Promising activities have been detected in phase II trials, and results of phase III clinical trials are awaited eagerly. PMID:20072701

  6. Proton therapy for pancreatic cancer

    PubMed Central

    Nichols, Romaine C; Huh, Soon; Li, Zuofeng; Rutenberg, Michael

    2015-01-01

    Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy. PMID:26380057

  7. [Proteasome inhibitors in cancer therapy].

    PubMed

    Romaniuk, Wioletta; Ołdziej, Agnieszka Ewa; Zińczuk, Justyna; Kłoczko, Janusz

    2015-01-01

    Proteasomes are multisubunit enzyme complexes. They contain three enzymatic active sites which are termed chymotrypsin-like, trypsin-like, and caspase-like. The elementary function of the proteasomes is degradation of damaged proteins. Proteasome inhibition leads to accumulation of damaged protein, which leads to caspase activation and cell death. This relationship is used in cancer therapy. Bortezomib is the first proteasome inhibitor approved by the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma. Carfilzomib belongs to the second generation of drugs, which was approved by the US FDA in 2012. Currently in the study phase there are four new inhibitors: ixazomib (MLN9780/MLN2238), delanzomib (CEP-18770), oprozomib (ONX0912/PR-047) and marizomib (NPI-0052). PMID:27259216

  8. Economic analysis of a phase III clinical trial evaluating the addition of total androgen suppression to radiation versus radiation alone for locally advanced prostate cancer (Radiation Therapy Oncology Group protocol 86-10)

    SciTech Connect

    Konski, Andre . E-mail: a_konski@fccc.edu; Sherman, Eric; Krahn, Murray; Bremner, Karen; Beck, J. Robert; Watkins-Bruner, Deborah; Pilepich, Michael

    2005-11-01

    Purpose: To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer, using a Monte Carlo simulation of a Markov Model. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT) alone or RT plus total androgen suppression (RTHormones) 2 months before and during RT for the treatment of locally advanced prostate cancer. A Markov model was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis took a payer's perspective. Transition probabilities from one state of health (i.e., with no disease progression or with hormone-responsive metastatic disease) to another were calculated from published rates pertaining to RTOG 86-10. Patients remained in one state of health for 1 year. Utility values for each health state and treatment were obtained from the literature. Distributions were sampled at random from the treatment utilities according to a second-order Monte Carlo simulation technique. Results: The mean expected cost for the RT-only treatments was $29,240 (range, $29,138-$29,403). The mean effectiveness for the RT-only treatment was 5.48 quality-adjusted life years (QALYs) (range, 5.47-5.50). The mean expected cost for RTHormones was $31,286 (range, $31,058-$31,555). The mean effectiveness was 6.43 QALYs (range, 6.42-6.44). Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at $2,153/QALY. Cost-effectiveness acceptability curve analysis resulted in a >80% probability that RTHormones is cost-effective. Conclusions: Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range.

  9. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  10. Pharmacogenomics: Biomarker-Directed Therapy for Bladder Cancer.

    PubMed

    Jones, Robert T; Felsenstein, Kenneth M; Theodorescu, Dan

    2016-02-01

    The clinical management of bladder cancer has seen little change over the last three decades and there is pressing need to identify more effective treatments for advanced disease. Low clinical use of neoadjuvant therapies stems from historical limitations in the ability to predict patients most likely to respond to combination chemotherapies. This article focuses on recent molecular and genetic studies, highlighting promising clinical trials and retrospective studies, and discusses emerging trials that use predictive biomarkers to match patients with therapies to which they are most likely to respond. The implementation of predictive genomic and molecular biomarkers will revolutionize urologic oncology and the clinical management of bladder cancer.

  11. Grand challenges in bioengineered nanorobotics for cancer therapy.

    PubMed

    Lenaghan, Scott C; Wang, Yongzhong; Xi, Ning; Fukuda, Toshio; Tarn, Tzyhjong; Hamel, William R; Zhang, Mingjun

    2013-03-01

    One of the grand challenges currently facing engineering, life sciences, and medicine is the development of fully functional nanorobots capable of sensing, decision making, and actuation. These nanorobots may aid in cancer therapy, site-specific drug delivery, circulating diagnostics, advanced surgery, and tissue repair. In this paper, we will discuss, from a bioinspired perspective, the challenges currently facing nanorobotics, including core design, propulsion and power generation, sensing, actuation, control, decision making, and system integration. Using strategies inspired from microorganisms, we will discuss a potential bioengineered nanorobot for cancer therapy.

  12. Biomedical nanomaterials for imaging-guided cancer therapy

    NASA Astrophysics Data System (ADS)

    Huang, Yuran; He, Sha; Cao, Weipeng; Cai, Kaiyong; Liang, Xing-Jie

    2012-09-01

    To date, even though various kinds of nanomaterials have been evaluated over the years in order to develop effective cancer therapy, there is still significant challenges in the improvement of the capabilities of nano-carriers. Developing a new theranostic nanomedicine platform for imaging-guided, visualized cancer therapy is currently a promising way to enhance therapeutic efficiency and reduce side effects. Firstly, conventional imaging technologies are reviewed with their advantages and disadvantages, respectively. Then, advanced biomedical materials for multimodal imaging are illustrated in detail, including representative examples for various dual-modalities and triple-modalities. Besides conventional cancer treatment (chemotherapy, radiotherapy), current biomaterials are also summarized for novel cancer therapy based on hyperthermia, photothermal, photodynamic effects, and clinical imaging-guided surgery. In conclusion, biomedical materials for imaging-guided therapy are becoming one of the mainstream treatments for cancer in the future. It is hoped that this review might provide new impetus to understand nanotechnology and nanomaterials employed for imaging-guided cancer therapy.

  13. Intelligent Nanoparticles for Advanced Drug Delivery in Cancer Treatment

    PubMed Central

    Spencer, David S.; Puranik, Amey S.; Peppas, Nicholas A.

    2015-01-01

    Treatment of cancer using nanoparticle-based approaches relies on the rational design of carriers with respect to size, charge, and surface properties. Polymer-based nanomaterials, inorganic materials such as gold, iron oxide, and silica as well as carbon based materials such as carbon nanotubes and graphene are being explored extensively for cancer therapy. The challenges associated with the delivery of these nanoparticles depend greatly on the type of cancer and stage of development. This review highlights design considerations to develop nanoparticle-based approaches for overcoming physiological hurdles in cancer treatment, as well as emerging research in engineering advanced delivery systems for the treatment of primary, metastatic, and multidrug resistant cancers. A growing understanding of cancer biology will continue to foster development of intelligent nanoparticle-based therapeutics that take into account diverse physiological contexts of changing disease states to improve treatment outcomes. PMID:25621200

  14. Phase I/II study of bortezomib in combination with carboplatin and bevacizumab as first line therapy in patients with advanced non-small cell lung cancer (NSCLC)

    PubMed Central

    Piperdi, Bilal; Walsh, William V; Bradley, Kendra; Zhou, Zheng; Bathini, Venu; Hanrahan-Boshes, Meredith; Hutchinson, Lloyd; Perez-Soler, Roman

    2013-01-01

    Purpose To establish the maximum tolerated dose (MTD) of weekly bortezomib in combination with fixed standard doses of carboplatin and bevacizumab and to estimate the efficacy (response rate and progression free survival) and safety of combination therapy with carboplatin, bortezomib and bevacizumab as first line therapy in patients with advanced NSCLC. Experimental Design Patients were assigned to three dose levels of weekly bortezomib with the fixed standard doses of carboplatin (AUC 6) and bevacizumab (15 mg/kg) q 3 wks using a standard phase I design. Bortezomib doses were 1.3 mg/m21.6 mg/m2 and 1.8 mg/m2 weekly on D1 and D8 of q 3wk cycle. A maximum of six cycles was administered. Patients with complete, partial response (PR) or stable disease were continued on single agent bevacizumab (15 mg/kg q 3 wks) as maintenance therapy. In phase II, either level III or MTD was administered to evaluate the efficacy and safety of the combination in first line treatment of advanced NSCLC. Results 16 patients were enrolled (3, 4 and 9 pts in dose level I, II and III respectively). There was no pre-defined dose limiting toxicity in cycle 1 in all 16 patients. The recommended phase II dose is bortezomib 1.8 mg/m2 weekly on day 1 and day 8 in combination with carboplatin AUC of 6 and bevacizumab 15 mg/kg on every 21 day cycle. Total of 9 patients were treated at the recommended phase II dose level. The most common treatment related grade 3/4 toxicities during the subsequent cycles were thrombocytopenia (58%), lymphopenia (25%), neutropenia (12%) and diarrhea (25%). The grade 1/2 neuropathy was seen in 7 out of 16 pts (44%). The response rate, PFS and OS in all patients were 37.5% (95%CI 13.8% - 61.2%), 5.0 months (m) (95%CI: 3.1-8.4), 9.9 m (95% CI: 8.2-14.1) and the 9 patients in phase II portion are 44% (95%CI 15.3% - 77.3%), 5.5 m (95%CI: 3.1-12.2) and 10.9 months (95%CI: 8.0-14.1). Conclusion The recommended phase II dose for this combination is: carboplatin AUC 6

  15. Applicability of RNA interference in cancer therapy: Current status.

    PubMed

    Maduri, S

    2015-01-01

    Cancer is a manifestation of dysregulated gene function arising from a complex interplay of oncogenes and tumor suppressor genes present in our body. Cancer has been constantly chased using various therapies but all in vain as most of them are highly effective only in the early stages of cancer. Recently, RNA interference (RNAi) therapy, a comparatively new entrant is evolving as a promising player in the battle against cancer due to its post-transcriptional gene silencing ability. The most alluring feature of this non-invasive technology lies in its utility in the cancer detection and the cancer treatment at any stage. Once this technology is fully exploited it can bring a whole new era of therapeutics capable of curing cancer at any stage mainly due to its ability to target the vital processes required for cell proliferation such as response to growth factors, nutrient uptake/synthesis, and energy generation. This therapy can also be used to treat stage IV cancer, the most difficult to treat till date, by virtue of its metastasis inhibiting capability. Recent research has also proved that cancer can even be prevented by proper modulation of physiological RNAi pathways and researchers have found that many nutrients, which are a part of routine diet, can effectively modulate these pathways and prevent cancer. Even after having all these advantages the potential of RNAi therapy could not be fully tapped earlier, due to many limitations associated with the administration of RNAi based therapeutics. However, recent advancements in this direction, such as the development of small interfering RNA (siRNA) tolerant to nucleases and the development of non-viral vectors such as cationic liposomes and nanoparticles, can overcome this obstacle and facilitate the clinical use of RNAi based therapeutics in the treatment of cancer. The present review focuses on the current status of RNAi therapeutics and explores their potential as future diagnostics and therapeutics against

  16. Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study.

    PubMed

    Tan, A R; Johannes, H; Rastogi, P; Jacobs, S A; Robidoux, A; Flynn, P J; Thirlwell, M P; Fehrenbacher, L; Stella, P J; Goel, R; Julian, T B; Provencher, L; Bury, M J; Bhatt, K; Geyer, C E; Swain, S M; Mamounas, E P; Wolmark, N

    2015-01-01

    This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA-C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.

  17. Polymeric Nanoparticles for Cancer Photodynamic Therapy.

    PubMed

    Conte, Claudia; Maiolino, Sara; Pellosi, Diogo Silva; Miro, Agnese; Ungaro, Francesca; Quaglia, Fabiana

    2016-01-01

    In chemotherapy a fine balance between therapeutic and toxic effects needs to be found for each patient, adapting standard combination protocols each time. Nanotherapeutics has been introduced into clinical practice for treating tumors with the aim of improving the therapeutic outcome of conventional therapies and of alleviating their toxicity and overcoming multidrug resistance. Photodynamic therapy (PDT) is a clinically approved, minimally invasive procedure emerging in cancer treatment. It involves the administration of a photosensitizer (PS) which, under light irradiation and in the presence of molecular oxygen, produces cytotoxic species. Unfortunately, most PSs lack specificity for tumor cells and are poorly soluble in aqueous media, where they can form aggregates with low photoactivity. Nanotechnological approaches in PDT (nanoPDT) can offer a valid option to deliver PSs in the body and to solve at least some of these issues. Currently, polymeric nanoparticles (NPs) are emerging as nanoPDT system because their features (size, surface properties, and release rate) can be readily manipulated by selecting appropriate materials in a vast range of possible candidates commercially available and by synthesizing novel tailor-made materials. Delivery of PSs through NPs offers a great opportunity to overcome PDT drawbacks based on the concept that a nanocarrier can drive therapeutic concentrations of PS to the tumor cells without generating any harmful effect in non-target tissues. Furthermore, carriers for nanoPDT can surmount solubility issues and the tendency of PS to aggregate, which can severely affect photophysical, chemical, and biological properties. Finally, multimodal NPs carrying different drugs/bioactive species with complementary mechanisms of cancer cell killing and incorporating an imaging agent can be developed. In the following, we describe the principles of PDT use in cancer and the pillars of rational design of nanoPDT carriers dictated by tumor and

  18. Silicon nanostructures for cancer diagnosis and therapy.

    PubMed

    Peng, Fei; Cao, Zhaohui; Ji, Xiaoyuan; Chu, Binbin; Su, Yuanyuan; He, Yao

    2015-01-01

    The emergence of nanotechnology suggests new and exciting opportunities for early diagnosis and therapy of cancer. During the recent years, silicon-based nanomaterials featuring unique properties have received great attention, showing high promise for myriad biological and biomedical applications. In this review, we will particularly summarize latest representative achievements on the development of silicon nanostructures as a powerful platform for cancer early diagnosis and therapy. First, we introduce the silicon nanomaterial-based biosensors for detecting cancer markers (e.g., proteins, tumor-suppressor genes and telomerase activity, among others) with high sensitivity and selectivity under molecular level. Then, we summarize in vitro and in vivo applications of silicon nanostructures as efficient nanoagents for cancer therapy. Finally, we discuss the future perspective of silicon nanostructures for cancer diagnosis and therapy.

  19. Multidrug Resistance Proteins (MRPs) and Cancer Therapy.

    PubMed

    Zhang, Yun-Kai; Wang, Yi-Jun; Gupta, Pranav; Chen, Zhe-Sheng

    2015-07-01

    The ATP-binding cassette (ABC) transporters are members of a protein superfamily that are known to translocate various substrates across membranes, including metabolic products, lipids and sterols, and xenobiotic drugs. Multidrug resistance proteins (MRPs) belong to the subfamily C in the ABC transporter superfamily. MRPs have been implicated in mediating multidrug resistance by actively extruding chemotherapeutic substrates. Moreover, some MRPs are known to be essential in physiological excretory or regulatory pathways. The importance of MRPs in cancer therapy is also implied by their clinical insights. Modulating the function of MRPs to re-sensitize chemotherapeutic agents in cancer therapy shows great promise in cancer therapy; thus, multiple MRP inhibitors have been developed recently. This review article summarizes the structure, distribution, and physiological as well as pharmacological function of MRP1-MRP9 in cancer chemotherapy. Several novel modulators targeting MRPs in cancer therapy are also discussed. PMID:25840885

  20. Multidrug Resistance Proteins (MRPs) and Cancer Therapy.

    PubMed

    Zhang, Yun-Kai; Wang, Yi-Jun; Gupta, Pranav; Chen, Zhe-Sheng

    2015-07-01

    The ATP-binding cassette (ABC) transporters are members of a protein superfamily that are known to translocate various substrates across membranes, including metabolic products, lipids and sterols, and xenobiotic drugs. Multidrug resistance proteins (MRPs) belong to the subfamily C in the ABC transporter superfamily. MRPs have been implicated in mediating multidrug resistance by actively extruding chemotherapeutic substrates. Moreover, some MRPs are known to be essential in physiological excretory or regulatory pathways. The importance of MRPs in cancer therapy is also implied by their clinical insights. Modulating the function of MRPs to re-sensitize chemotherapeutic agents in cancer therapy shows great promise in cancer therapy; thus, multiple MRP inhibitors have been developed recently. This review article summarizes the structure, distribution, and physiological as well as pharmacological function of MRP1-MRP9 in cancer chemotherapy. Several novel modulators targeting MRPs in cancer therapy are also discussed.

  1. Cancer stem cells, cancer cell plasticity and radiation therapy.

    PubMed

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.

  2. Cancer Stem Cells, Cancer Cell Plasticity and Radiation Therapy

    PubMed Central

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    Summary Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. PMID:25025713

  3. Focus Issue: Cell biology meets cancer therapy.

    PubMed

    Gough, Nancy R

    2016-02-16

    Cells are the targets of anticancer therapy, whether the therapy is directed at the tumor cells themselves or the cells of the immune system. Articles in this issue and in the 2015 Science Signaling archives provide insights into what makes a cell responsive to therapy and how understanding the cellular processes affected by the drugs (including endosomal trafficking and response to proteotoxic stress) can lead to personalized cancer therapies, thereby minimizing side effects and ineffective treatment strategies.

  4. [Pharmacological therapy of cancer anorexia-cachexia].

    PubMed

    Cardona, D

    2006-05-01

    Anorexia is one of the most common symptoms of patients with advanced cancer and it presents as loss of appetite due to satiety. On the other hand, cachexia is described in those patients with unwanted weight loss. Cancerous processes produce an energy unbalance by decreased food intake and increased catabolism, resulting in a clearly negative balance. Several factors determining cachexia are observed, from metabolic unbalances produced by tumoral products and endocrine impairments or the inflammatory response produced by cytokines, all of them leading to higher lipolysis, loss of muscle protein, and anorexia. Besides, causes of anorexia are multiple, from chemotherapy agents, radiotherapy, or immunotherapy, which may produce different degrees of nausea, vomiting, diarrhea, and also leading to impairments of taste and smell, to obstruction of the digestive tract, pain, depression, constipation, etc. From the knowledge of the different mechanisms producing the anorexia-cachexia syndrome, hypercaloric diets for artificial nutrition have been studied with varying success, and different drugs with a positive effect on appetite gain such as progestogens, steroids, and with lesser clinical evidence cannabinoids, cyproheptadine, mirtazapine (antidepressant), and olanzapine (antipsychotic). Other drugs have been studied because of their anti-inflammatory properties, anti-cytokine, such as melatonin, polyunsaturated omega-3 fatty acids, pentoxifylline, and thalidomide; with the exception of the latter, clinical data are still scant for daily usage. Similarly happens with testosterone-derived anabolic drugs or with metabolism inhibitors such as hydrazine sulfate. With no doubt, progestogens, especially megestrol, and corticosteroids will be first-line therapies for anorexia-cachexia syndrome to stimulate the appetite and increase weight (megestrol), and have an effect on quality of life improvement and comfort in patients with advanced cancer.

  5. Mesenchymal stem cell: a new horizon in cancer gene therapy.

    PubMed

    Mohammadi, M; Jaafari, M R; Mirzaei, H R; Mirzaei, H

    2016-09-01

    Cancer is one of the main problems in public health worldwide. Despite rapid advances in the diagnosis and treatment of cancer, the efficacy of current treatment strategies is still limited. There are promising new results in animal models whereby mesenchymal stem cells (MSCs) can be used as vehicles for targeted therapies. The use of MSCs as therapeutic biological vehicles in cell therapy has several advantages, including immune-silence, tumor tropism, easy and rapid isolation, ex vivo expansion, multilineage differentiation and the capacity to deliver a number of therapeutic agents. Some studies have shown that the microenvironment of the tumor provides a preferential niche for homing and survival of MSCs. Here, we have highlighted various applications of MSCs in cancer gene therapy. PMID:27650780

  6. Targeting copper in cancer therapy: 'Copper That Cancer'.

    PubMed

    Denoyer, Delphine; Masaldan, Shashank; La Fontaine, Sharon; Cater, Michael A

    2015-11-01

    Copper is an essential micronutrient involved in fundamental life processes that are conserved throughout all forms of life. The ability of copper to catalyze oxidation-reduction (redox) reactions, which can inadvertently lead to the production of reactive oxygen species (ROS), necessitates the tight homeostatic regulation of copper within the body. Many cancer types exhibit increased intratumoral copper and/or altered systemic copper distribution. The realization that copper serves as a limiting factor for multiple aspects of tumor progression, including growth, angiogenesis and metastasis, has prompted the development of copper-specific chelators as therapies to inhibit these processes. Another therapeutic approach utilizes specific ionophores that deliver copper to cells to increase intracellular copper levels. The therapeutic window between normal and cancerous cells when intracellular copper is forcibly increased, is the premise for the development of copper-ionophores endowed with anticancer properties. Also under investigation is the use of copper to replace platinum in coordination complexes currently used as mainstream chemotherapies. In comparison to platinum-based drugs, these promising copper coordination complexes may be more potent anticancer agents, with reduced toxicity toward normal cells and they may potentially circumvent the chemoresistance associated with recurrent platinum treatment. In addition, cancerous cells can adapt their copper homeostatic mechanisms to acquire resistance to conventional platinum-based drugs and certain copper coordination complexes can re-sensitize cancer cells to these drugs. This review will outline the biological importance of copper and copper homeostasis in mammalian cells, followed by a discussion of our current understanding of copper dysregulation in cancer, and the recent therapeutic advances using copper coordination complexes as anticancer agents.

  7. HER2-targeted therapies in breast cancer

    PubMed Central

    Nahta, Rita

    2013-01-01

    HER2 was acknowledged as an important therapeutic target in breast cancer more than twenty-five years ago. Subsequently, significant basic science and translational discoveries have resulted in the approval of four HER2-targeted therapies over the past fifteen years. This editorial discusses future challenges regarding selection and development of treatments for HER2-positive breast cancer, which can only be met by continuing to support research efforts into the basic mechanisms by which cancer cells escape targeted therapies. Identifying specific molecular mechanisms underlying the sensitivity or resistance to each HER2-targeted agent will ultimately allow individualized therapy for each patient. PMID:23565676

  8. Cardiotoxicity associated with targeted cancer therapies

    PubMed Central

    CHEN, ZI; AI, DI

    2016-01-01

    Compared with traditional chemotherapy, targeted cancer therapy is a novel strategy in which key molecules in signaling pathways involved in carcinogenesis and tumor spread are inhibited. Targeted cancer therapy has fewer adverse effects on normal cells and is considered to be the future of chemotherapy. However, targeted cancer therapy-induced cardiovascular toxicities are occasionally critical issues in patients who receive novel anticancer agents, such as trastuzumab, bevacizumab, sunitinib and imatinib. The aim of this review was to discuss these most commonly used drugs and associated incidence of cardiotoxicities, including left ventricular dysfunction, heart failure, hypertension and thromboembolic events, as well as summarize their respective molecular mechanisms of cardiovascular adverse effects. PMID:27123262

  9. Recent advances in neutron capture therapy (NCT)

    SciTech Connect

    Fairchild, R.G.

    1985-01-01

    The application of the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction to cancer radiotherapy (Neutron Capture therapy, or NCT) has intrigued investigators since the discovery of the neutron. This paper briefly summarizes data describing recently developed boronated compounds with evident tumor specificity and extended biological half-lives. The implication of these compounds to NCT is evaluated in terms of Therapeutic Gain (TG). The optimization of NCT using band-pass filtered beams is described, again in terms of TG, and irradiation times with these less intense beams are estimated. 24 refs., 3 figs., 3 tabs.

  10. Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

    ClinicalTrials.gov

    2014-04-21

    Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Therapy-related Toxicity

  11. The Ongoing History of Thermal Therapy for Cancer

    PubMed Central

    Glazer, Evan S.; Curley, Steven A.

    2011-01-01

    Through 5,000 years of practice, physicians, surgeons, clergy, or lay people have utilized thermal therapy to treat mass lesions now known as cancer. The methods have changed dramatically over this time span and certainly the techniques have improved the efficacy and safety, but fundamentally, hyperthermic therapy is usually a local or regional treatment for most cancer patients. Fortunately, hyperthermia used in combination with chemotherapy or ionizing radiation continues to improve outcomes. We will briefly describe the historic role of hyperthermia in cancer care as well as modern expectations based on technological advancements. In particular, we will focus on the role of hyperthermia for cancers that do not have other, more effective treatments. PMID:21377580

  12. Meditation as a complementary therapy in cancer.

    PubMed

    Tacón, Anna M

    2003-01-01

    The number of cancer patients seeking complementary therapies to deal with their disease has increased steadily in recent decades. Complementary therapies can be helpful to cancer patients because they address some of the pervasive psychosocial difficulties associated with this disease. One mind-body technique is meditation. While programs using meditation have been developed for specific health populations, such as heart disease and addictions, an equivalent, well-established program for cancer patients is lacking. This article reviews the literature and proposes a complementary meditation program designed specifically for use with cancer patients.

  13. Recent advances in chemotherapy for advanced gastric cancer.

    PubMed

    Kim, Jong Gwang; Chung, Ho Young; Yu, Wansik

    2010-07-15

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the choice of optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration, with a median survival of approximately 7-11 mo and survival at 2 years rarely more than 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, several molecular targeting agents are now under evaluation in international randomized studies, and trastuzumab, an anti-HER2 monoclonal antibody, has shown antitumor activity against HER-2 positive AGC. However, this benefit is limited to only about 20% of patients with AGC (patients with HER-2 positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of predictive and prognostic molecular markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

  14. Frontiers in Suicide Gene Therapy of Cancer

    PubMed Central

    Malecki, Marek

    2012-01-01

    The National Cancer Institute (NCI) and the American Cancer Society (ACS) predict that 1,638,910 men and women will be diagnosed with cancer in the USA in 2012. Nearly 577,190 patients will die of cancer of all sites this year. Patients undergoing current systemic therapies will suffer multiple side effects from nausea to infertility. Potential parents, when diagnosed with cancer, will have to deposit oocytes or sperm prior to starting systemic radiation or chemo-therapy for the future genetic testing and in vitro fertilization, while trying to avoid risks of iatrogenic mutations in their germ cells. Otherwise, children of parents treated with systemic therapies, will be at high risk of developing genetic disorders. According to these predictions, this year will carry another, very poor therapeutic record again. The ultimate goal of cancer therapy is the complete elimination of all cancer cells, while leaving all healthy cells unharmed. One of the most promising therapeutic strategies in this regard is cancer suicide gene therapy (CSGT), which is rapidly progressing into new frontiers. The therapeutic success, in CSGT, is primarily contingent upon precision in delivery of the therapeutic transgenes to the cancer cells only. This is addressed by discovering and targeting unique or / and over-expressed biomarkers displayed on the cancer cells and cancer stem cells. Specificity of cancer therapeutic effects is further enhanced by designing the DNA constructs, which put the therapeutic genes under the control of the cancer cell specific promoters. The delivery of the suicidal genes to the cancer cells involves viral, as well as synthetic vectors, which are guided by cancer specific antibodies and ligands. The delivery options also include engineered stem cells with tropisms towards cancers. Main mechanisms inducing cancer cells’ deaths include: transgenic expression of thymidine kinases, cytosine deaminases, intracellular antibodies, telomeraseses, caspases, DNases

  15. CROI 2016: Advances in Antiretroviral Therapy.

    PubMed

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa. PMID:27398863

  16. Nanoscience and Nanotechnology: From Energy Applications to Advanced Medical Therapies

    ScienceCinema

    Tijana Rajh

    2016-07-12

    Dr. Rajh will present a general talk on nanotechnology – an overview of why nanotechnology is important and how it is useful in various fields. The specific focus will be on Solar energy conversion, environmental applications and advanced medical therapies. She has broad expertise in synthesis and characterization of nanomaterials that are used in nanotechnology including novel hybrid systems connecting semiconductors to biological molecules like DNA and antibodies. This technology could lead to new gene therapy procedures, cancer treatments and other medical applications. She will also discuss technologies made possible by organizing small semiconductor particles called quantum dots, materials that exhibit a rich variety of phenomena that are size and shape dependent. Development of these new materials that harnesses the unique properties of materials at the 1-100 nanometer scale resulted in the new field of nanotechnology that currently affects many applications in technological and medical fields.

  17. Progress in neutron capture therapy for cancer

    SciTech Connect

    Allen, B.J.; Harrington, B.V. ); Moore, D.E. )

    1992-01-01

    Prognosis for some cancers is good, but for others, few patients will survive 12 months. This latter group of cancers is characterised by a proclivity to disseminate malignant cells in the host organ. In some cases systemic metastases occur, but in other cases, failure to achieve local control results in death. First among these cancers are the high grade brain tumours, astrocytoma 3,4 and glioblastoma multiforme. Local control of these tumors should lead to cure. Other cancers melanoma metastatic to the brain, for which a useful palliative therapy is not yet available, and pancreatic cancer for which localised control at an early stage could bring about improved prognosis. Patients with these cancers have little grounds for hope. Our primary objective is to reverse this situation with Neutron Capture Therapy (NCT). The purpose of this fourth symposium is to hasten the day whereby patients with these cancers can reasonably hope for substantial remissions.

  18. Progress in neutron capture therapy for cancer

    SciTech Connect

    Allen, B.J.; Harrington, B.V.; Moore, D.E.

    1992-09-01

    Prognosis for some cancers is good, but for others, few patients will survive 12 months. This latter group of cancers is characterised by a proclivity to disseminate malignant cells in the host organ. In some cases systemic metastases occur, but in other cases, failure to achieve local control results in death. First among these cancers are the high grade brain tumours, astrocytoma 3,4 and glioblastoma multiforme. Local control of these tumors should lead to cure. Other cancers melanoma metastatic to the brain, for which a useful palliative therapy is not yet available, and pancreatic cancer for which localised control at an early stage could bring about improved prognosis. Patients with these cancers have little grounds for hope. Our primary objective is to reverse this situation with Neutron Capture Therapy (NCT). The purpose of this fourth symposium is to hasten the day whereby patients with these cancers can reasonably hope for substantial remissions.

  19. Nanotherapy for Cancer: Targeting and Multifunctionality in the Future of Cancer Therapies

    PubMed Central

    2015-01-01

    Cancer continues to be a prevalent and lethal disease, despite advances in tumor biology research and chemotherapy development. Major obstacles in cancer treatment arise from tumor heterogeneity, drug resistance, and systemic toxicities. Nanoscale delivery systems, or nanotherapies, are increasing in importance as vehicles for antineoplastic agents because of their potential for targeting and multifunctionality. We discuss the current field of cancer therapy and potential strategies for addressing obstacles in cancer treatment with nanotherapies. Specifically, we review the strategies for rationally designing nanoparticles for targeted, multimodal delivery of therapeutic agents. PMID:25984571

  20. Missed Radiation Therapy and Cancer Recurrence

    Cancer.gov

    Patients who miss radiation therapy sessions during cancer treatment have an increased risk of their disease returning, even if they eventually complete their course of radiation treatment, according to a new study.

  1. Local Therapy Indications in the Management of Patients with Oligometastatic Non-Small Cell Lung Cancer.

    PubMed

    Miller, Douglas A; Krasna, Mark J

    2016-07-01

    Advances in surgical, radiation, and interventional radiology therapies carry a reduction in morbidity associated with therapy. Aggressive management of patients with oligometastatic non-small cell lung cancer offers the potential for improved disease-free survival and quality of life compared with traditional systemic therapy alone. PMID:27261919

  2. Long-term follow-up of cancer patients treated with gene therapy medicinal products.

    PubMed

    Galli, Maria Cristina

    2012-06-01

    European Union requirements are discussed for the long-term follow-up of advanced therapy medicinal products, as well as how they can be applied to cancer patients treated with gene therapy medicinal products in the context of clinical trials, as described in a specific guideline issued by Gene Therapy Working Party at the European Medicine Agency.

  3. Integrated Molecular Profiling in Advanced Cancers Trial

    ClinicalTrials.gov

    2016-08-19

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  4. [Induction chemotherapy for locally advanced cervical cancer].

    PubMed

    Morkhov, K Yu; Nechushkina, V M; Kuznetsov, V V

    2015-01-01

    The main methods of treatment for cervical cancer are surgery, radiotherapy or their combination. During past two decades chemotherapy are increasingly being used not only in patients with disseminated forms of this disease but also in patients undergoing chemoradiotherapy or as induction therapy. Possibilities of adjuvant chemotherapy for cervical cancer are being studied. According to A.D.Kaprin and V.V. Starinskiy in 2013 in Russia, 32% of patients with newly diagnosed cervical cancer underwent only radiation therapy, 32%--combined or complex treatment, 27.3%--only surgery, and just 8.7%--chemoradiotherapy. PMID:26087600

  5. Personalized Therapy of Small Cell Lung Cancer.

    PubMed

    Schneider, Bryan J; Kalemkerian, Gregory P

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive, poorly differentiated neuroendocrine carcinoma with distinct clinical, pathological and molecular characteristics. Despite robust responses to initial chemotherapy and radiation, the prognosis of patients with SCLC remains poor with an overall 5-year survival rate of less than 10 %. Despite the fact that numerous molecularly targeted approaches have thus far failed to demonstrate clinical utility in SCLC, further advances will rely on better definition of the biological pathways that drive survival, proliferation and metastasis. Recent next-generation, molecular profiling studies have identified many new therapeutic targets in SCLC, as well as extreme genomic instability which explains the high degree of resistance. A wide variety of anti-angiogenic agents, growth factor inhibitors, pro-apoptotic agents, and epigenetic modulators have been evaluated in SCLC and many studies of these strategies are on-going. Perhaps the most promising approaches involve agents targeting cancer stem cell pathways and immunomodulatory drugs that interfere with the PD1 and CTLA-4 pathways. SCLC offers many barriers to the development of successful therapy, including limited tumor samples, inadequate preclinical models, high mutational burden, and aggressive tumor growth which impairs functional status and hampers enrollment on clinical trials. PMID:26703804

  6. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  7. Prostate Cancer Stem Cells: Research Advances.

    PubMed

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  8. Electrospun nanofibers for cancer diagnosis and therapy.

    PubMed

    Chen, Zhou; Chen, Zhaofeng; Zhang, Aili; Hu, Jiaming; Wang, Xinmei; Yang, Zhaogang

    2016-06-24

    The advent of nanotechnology has provided unprecedented opportunities for nanomedicine. Electrospun nanofibers have some astounding features such as high loading capacity, extremely large surface area and porosity, high encapsulation efficiency, ease of modification, combination of diverse therapies, low cost and great benefits. These remarkable structure-dependent properties have far reaching application potential in cancer diagnosis and therapy such as ultra-sensitive sensing systems for point-of-care cancer detection, targeted cancer cell capture, and functional and smart anticancer drug delivery systems. This review summarizes the principal mechanism of electrospun nanofibers and a variety of modified electrospun nanofibers, illustrates their application in biosensors for cancer detection, and enumerates their application in implantable drug delivery for cancer therapy. PMID:27048889

  9. Changing strategies for target therapy in gastric cancer

    PubMed Central

    Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer. PMID:26811656

  10. Molecular targeted therapy for the treatment of gastric cancer.

    PubMed

    Xu, Wenting; Yang, Zhen; Lu, Nonghua

    2016-01-04

    Despite the global decline in the incidence and mortality of gastric cancer, it remains one of the most common malignant tumors of the digestive system. Although surgical resection is the preferred treatment for gastric cancer, chemotherapy is the preferred treatment for recurrent and advanced gastric cancer patients who are not candidates for reoperation. The short overall survival and lack of a standard chemotherapy regimen make it important to identify novel treatment modalities for gastric cancer. Within the field of tumor biology, molecular targeted therapy has attracted substantial attention to improve the specificity of anti-cancer efficacy and significantly reduce non-selective resistance and toxicity. Multiple clinical studies have confirmed that molecular targeted therapy acts on various mechanisms of gastric cancer, such as the regulation of epidermal growth factor, angiogenesis, immuno-checkpoint blockade, the cell cycle, cell apoptosis, key enzymes, c-Met, mTOR signaling and insulin-like growth factor receptors, to exert a stronger anti-tumor effect. An in-depth understanding of the mechanisms that underlie molecular targeted therapies will provide new insights into gastric cancer treatment.

  11. Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

    PubMed

    Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

    2016-11-01

    The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc.

  12. Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

    PubMed Central

    Blumenthal, Gideon M.; Karuri, Stella W.; Zhang, Hui; Zhang, Lijun; Khozin, Sean; Kazandjian, Dickran; Tang, Shenghui; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2015-01-01

    Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect. PMID:25667291

  13. Gene therapy for cancer: from the laboratory to the patient.

    PubMed

    Kouraklis, G

    2000-06-01

    Gene therapy is a new form of therapeutic intervention with applications in many areas of medical treatment. There are still many technical difficulties to be overcome, but recent advances in the molecular and cellular biology of gene transfer have made it likely that gene therapy will soon start to play an increasing role in clinical practice and particularly in the treatment of cancer. The first clinical gene transfer in an approved protocol took place exactly 10 years ago, and it was for the transfer of gene-marked immune cells into patients with advanced cancer. Now there are 218 active clinical protocols in the United States, and they have involved over 2000 patients worldwide. Among the conditions and diseases for which gene transfer is being tried as treatment, cancer comes first with 130 clinical trials. Fundamental research in the mechanisms of cancer and the development of molecular biology tools are crucial for the success of the treatments in the future. The identification of tumor rejection antigens from a variety of cancers and the immune response that is defective in cancer patients are important topics for future studies. The evaluation of gene therapy combinations involving use of tumor suppressor genes and constructs that inactivate oncogenes is also another important area for future research. The future improvement of present viruses as well as the use of new viral vectors will likely expand the applicability and efficacy of gene therapy. During the next decade technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful clinical practice of gene therapy.

  14. Pharmacogenetics and pharmacogenomics as tools in cancer therapy.

    PubMed

    Rodríguez-Vicente, Ana E; Lumbreras, Eva; Hernández, Jesus M; Martín, Miguel; Calles, Antonio; Otín, Carlos López; Algarra, Salvador Martín; Páez, David; Taron, Miquel

    2016-03-01

    Pharmacogenetics and pharmacogenomics (PGx) are rapidly growing fields that aim to elucidate the genetic basis for the interindividual differences in drug response. PGx approaches have been applied to many anticancer drugs in an effort to identify relevant inherited or acquired genetic variations that may predict patient response to chemotherapy and targeted therapies. In this article, we discuss the advances in the field of cancer pharmacogenetics and pharmacogenomics, driven by the recent technological advances and new revolutionary massive sequencing technologies and their application to elucidate the genetic bases for interindividual drug response and the development of biomarkers able to personalize drug treatments. Specifically, we present recent progress in breast cancer molecular classifiers, cell-free circulating DNA as a prognostic and predictive biomarker in cancer, patient-derived tumor xenograft models, chronic lymphocytic leukemia genomic landscape, and current pharmacogenetic advances in colorectal cancer. This review is based on the lectures presented by the speakers of the symposium "Pharmacogenetics and Pharmacogenomics as Tools in Cancer Therapy" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF), held in Madrid (Spain) on April 21, 2015.

  15. Photodynamic therapy for the treatment of non-small cell lung cancer.

    PubMed

    Simone, Charles B; Friedberg, Joseph S; Glatstein, Eli; Stevenson, James P; Sterman, Daniel H; Hahn, Stephen M; Cengel, Keith A

    2012-02-01

    Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described.

  16. Adjuvant therapy in breast cancer and venous thromboembolism.

    PubMed

    Mandalà, Mario; Tondini, Carlo

    2012-10-01

    Breast cancer patients are considered to be at relatively low risk of developing a TEE. The highest incidence of VTE events occurs in metastatic breast cancer patients likely due to extension of disease, immobility for pathologic bone fractures, cancer cachexia and venous compression by the tumour mass. Although thrombosis is less common in patients with early stage cancer compared to those with more advanced disease, it does occur and is clinically challenging. The adjuvant setting is of particular interest in order to assess the specific thrombogenic potential of systemic chemotherapy, because of the low tumor burden with only microscopic tumor foci at the time of treatment administration. This review summarizes risk factors, incidence and strategies to avoid VTE in breast cancer patients receiving adjuvant therapy.

  17. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil; Thompson, Lora M.; Yue, Binglin; Stevens, Craig W.; Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee; Kim, Sungjune; Chiappori, Alberto

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  18. Major clinical research advances in gynecologic cancer in 2014.

    PubMed

    Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

    2015-04-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review. PMID:25872896

  19. Testosterone Replacement Therapy and Prostate Cancer Incidence

    PubMed Central

    2015-01-01

    While early studies demonstrated a positive association between testosterone and prostate cancer, evidence on the nature of the relationship has evolved with time and newer data. Studies examining links between baseline testosterone levels as well as testosterone therapy and incident prostate cancer, reveal a more complex relationship. Moreover, investigators have reported their initial experiences with supplementing testosterone in men with a history of both treated and untreated prostate cancer. PMID:26770932

  20. Nausea and vomiting in advanced cancer.

    PubMed

    Gordon, Pamela; LeGrand, Susan B; Walsh, Declan

    2014-01-01

    Nausea and vomiting are very common symptoms in cancer both treatment and non-treatment related. Many complications of advanced cancer such as gastroparesis, bowel and outlet obstructions, and brain tumors may have nausea and vomiting or either symptom alone. In a non-obstructed situation, nausea may be more difficult to manage and is more objectionable to patients. There is little research on management of these symptoms except the literature on chemotherapy induced nausea where guidelines exist. This article will review the etiologies of nausea and vomiting in advanced cancer and the medications which have been used to treat them. An etiology based protocol to approach the symptom is outlined.

  1. Bacteria in cancer therapy: a novel experimental strategy.

    PubMed

    Patyar, S; Joshi, R; Byrav, D S Prasad; Prakash, A; Medhi, B; Das, B K

    2010-03-23

    Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful results in vivo yet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment.

  2. Dance as a therapy for cancer prevention.

    PubMed

    Aktas, Gurbuz; Ogce, Filiz

    2005-01-01

    Even though the field of medicine has developed tremendously, the wide variety of cancer is still among chronic and life threatening disease today. Therefore, the specialists constantly research and try every possible way to find cure or preventive ways to stop its further development. For this reason, studies concerning the chronic disease such as cancer have been spread to many different fields. In this regard, many other alternative ways besides medicine, are used in prevention of cancer. Nutritional therapy, herbal therapy, sportive activities, art therapy, music therapy, dance therapy, imagery, yoga and acupuncture can be given as examples. Among these, dance/movement therapy which deals with individuals physical, emotional, cognitive as well as social integration is widely used as a popular form of physical activity. The physical benefits of dance therapy as exercise are well documented. Studies have shown that physical activity is known to increase special neurotransmitter substances in the brain (endorphins), which create a state of well-being. And total body movement such as dance enhances the functions of other body systems, such as circulatory, respiratory, skeletal, and muscular systems. Regarding its unique connection to the field of medicine, many researches have been undertaken on the effects of dance/movement therapy in special settings with physical problems such as amputations, traumatic brain injury, and stroke, chronic illnesses such as anorexia, bulimia, cancer, Alzheimer's disease, cystic fibrosis, heart disease, diabetes, asthma, AIDS, and arthritis. Today dance/movement therapy is a well recognized form of complementary therapy used in hospitals as well as at the comprehensive clinical cancer centres. PMID:16236009

  3. [Adjuvant drug therapies for breast cancer].

    PubMed

    Huovinen, Riikka; Auvinen, Päivi; Mattson, Johanna; Joensuu, Heikki

    2015-01-01

    Most breast cancers are hormone receptor positive and exhibit a slow growth pattern. Based on biological properties, breast cancers are divided into four different biological subtypes. Furthermore, these subtypes are indicative of the risk of recurrence, which is also influenced by the size of the tumor and extension to lymph nodes. Postoperative adjuvant drug therapy is chosen on the basis of the biological type. Chemotherapy can be used in all subtypes. Hormonal therapies are used exclusively for the treatment of hormone receptor positive breast cancer. Trastuzumab antibody belongs to the treatment of the HER2 positive subtype. PMID:26245052

  4. Ovarian cancer: emerging molecular-targeted therapies

    PubMed Central

    Sourbier, Carole

    2012-01-01

    With about 22,000 new cases estimated in 2012 in the US and 15,500 related deaths, ovarian cancer is a heterogeneous and aggressive disease. Even though most of patients are sensitive to chemotherapy treatment following surgery, recurring disease is almost always lethal, and only about 30% of the women affected will be cured. Thanks to a better understanding of the molecular mechanisms underlying ovarian cancer malignancy, new therapeutic options with molecular-targeted agents have become available. This review discusses the rationale behind molecular-targeted therapies and examines how newly identified molecular targets may enhance personalized therapies for ovarian cancer patients. PMID:22807625

  5. Counseling Intervention in Cancer Therapy.

    ERIC Educational Resources Information Center

    Pusateri-Vlach, Nancy F.; Moracco, John C.

    1981-01-01

    Recounts the history of cancer treatment to illustrate the long-standing tradition of a holistic approach to the investigation and treatment of cancer, discusses the growing emphasis on holistic cancer treatment and the importance of counseling in such treatment. (Author)

  6. Stereotactic body radiation therapy for lung cancer: achievements and perspectives.

    PubMed

    Hiraoka, Masahiro; Matsuo, Yukinori; Takayama, Kenji

    2010-09-01

    Stereotactic body radiation therapy is a new treatment modality where narrow beams from several directions focus on the target while sparing the adjacent normal tissues with high accuracy. This technique basically derived from that of radiosurgery for intracranial lesions allows us to deliver high dose to the target leading to high control of the tumor without causing significant cytotoxicities associated with the treatment. Early-stage non-small cell lung cancers are regarded as most appropriate malignancies for this modality and accordingly have most intensively been investigated. With many encouraging outcomes in retrospective studies, several prospective clinical trials have been started world-wide. Japan Clinical Oncology Group protocol 0403 is a phase II trial of stereotactic body radiation therapy for T1N0M0 non-small cell lung cancer including both inoperable and operable patients. The results for operable patients are to be disclosed this year after 3 years of follow-up. It is highly probable that stereotactic body radiation therapy can be a standard treatment modality for inoperable patients for early-stage non-small cell lung cancer. The role of stereotactic body radiation therapy for operable patients is expected to be clarified by the outcomes of coming clinical trials. Tremendous advance in stereotactic body radiation therapy is expected when four-dimensional radiation therapy coping with tumor movement is realized. Among several approaches, tumor tracking appears most ideal. The new image-guided radiotherapy system which has the capability of tumor tracking has been developed in Japan.

  7. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    PubMed Central

    Berman, Abigail T.; St. James, Sara; Rengan, Ramesh

    2015-01-01

    Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning. PMID:26147335

  8. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions.

    PubMed

    Berman, Abigail T; James, Sara St; Rengan, Ramesh

    2015-01-01

    Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning. PMID:26147335

  9. Optimizing systemic therapy for bladder cancer.

    PubMed

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  10. Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

    PubMed Central

    Nomura, Takeo; Mimata, Hiromitsu

    2012-01-01

    A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with cancer control. Several techniques of focal therapy have potential for isolated ablation of a tumor focus with sparing of uninvolved surround tissue demonstrating excellent short-term cancer control and a favorable patient's quality of life. However, to date, tissue ablation has mostly used for near-whole prostate gland ablation without taking advantage of accompanying the technological capabilities. The available ablative technologies include cryotherapy, high-intensity focused ultrasound (HIFU), and vascular-targeted photodynamic therapy (VTP). Despite the interest in focal therapy, this technology has not yet been a well-established procedure nor provided sufficient data, because of the lack of randomized trial comparing the efficacy and morbidity of the standard treatment options. In this paper we briefly summarize the recent data regarding focal therapy for prostate cancer and these new therapeutic modalities. PMID:22593764

  11. Theranostic Imaging of Cancer Gene Therapy.

    PubMed

    Sekar, Thillai V; Paulmurugan, Ramasamy

    2016-01-01

    Gene-directed enzyme prodrug therapy (GDEPT) is a promising therapeutic approach for treating cancers of various phenotypes. This strategy is independent of various other chemotherapeutic drugs used for treating cancers where the drugs are mainly designed to target endogenous cellular mechanisms, which are different in various cancer subtypes. In GDEPT an external enzyme, which is different from the cellular proteins, is expressed to convert the injected prodrug in to a toxic metabolite, that normally kill cancer cells express this protein. Theranostic imaging is an approach used to directly monitor the expression of these gene therapy enzymes while evaluating therapeutic effect. We recently developed a dual-GDEPT system where we combined mutant human herpes simplex thymidine kinase (HSV1sr39TK) and E. coli nitroreductase (NTR) enzyme, to improve therapeutic efficiency of cancer gene therapy by simultaneously injecting two prodrugs at a lower dose. In this approach we use two different prodrugs such as ganciclovir (GCV) and CB1954 to target two different cellular mechanisms to kill cancer cells. The developed dual GDEPT system was highly efficacious than that of either of the system used independently. In this chapter, we describe the complete protocol involved for in vitro and in vivo imaging of therapeutic cancer gene therapy evaluation. PMID:27424910

  12. [Development of ultrasonic cancer therapy using ultrasound sensitive liposome].

    PubMed

    Suzuki, Ryo; Oda, Yusuke; Utoguchi, Naoki; Maruyama, Kazuo

    2010-12-01

    Ultrasound (US) has been utilized as a useful tool for diagnosis and therapy. US mediated drug and gene delivery is paid to attention as a non-invasive system. The combination of US and microbubbles generated microjet stream by inducing disruption of bubbles and resulted in enhancing permeability of cell membrane. This phenomenon has been utilized as driving force for drug and gene delivery. Recently, we developed ultrasound sensitive liposome [Bubble liposome (BL)] containing perfluoropropane gas. US combined with BL could effectively transfer gene in vivo compared to conventional cationic liposomes. Using this method, we succeeded to obtain a therapeutic effect in cancer gene therapy with Interleukin-12 corded plasmid DNA. Therefore, it is expected that US combined with BL might be a useful non-viral vector system. From this result, the fusion of liposomal and ultrasound technologies would be important for establishment of advanced cancer therapy.

  13. Cancer Nanomedicine: From Targeted Delivery to Combination Therapy

    PubMed Central

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-01-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of a variety of diseases, including cancer. The unique properties of nanoparticles, such as large surface-to volume ratio, small size, the ability to encapsulate a variety of drugs, and tunable surface chemistry, gives them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make nanoparticles a mode of treatment potentially superior to conventional cancer therapies. This article highlights the most recent developments in cancer treatment using nanoparticles as drug-delivery vehicles, including promising opportunities in targeted and combination therapy. PMID:25656384

  14. Recent advances in immuno-oncology and its application to urological cancers.

    PubMed

    Mataraza, Jennifer M; Gotwals, Philip

    2016-10-01

    Recent advances in immuno-oncology have the potential to transform the practice of medical oncology. Antibodies directed against negative regulators of T-cell function (checkpoint inhibitors), engineered cell therapies and innate immune stimulators, such as oncolytic viruses, are effective in a wide range of cancers. Immune'based therapies have had a clinically meaningful impact on the treatment of advanced melanoma, and the lessons regarding use of single agents and combinations in melanoma may be applicable to the treatment of urological cancers. Checkpoint inhibitors, cytokine therapy and therapeutic vaccines are already showing promise in urothelial bladder cancer, renal cell carcinoma and prostate cancer. Critical areas of future immuno-oncology research include the prospective identification of patients who will respond to current immune-based cancer therapies and the identification of new therapeutic agents that promote immune priming in tumours, and increase the rate of durable clinical responses.

  15. Pancreatic cancer: systemic combination therapies for a heterogeneous disease.

    PubMed

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo

    2014-01-01

    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  16. Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

    SciTech Connect

    Harima, Yoko; Ikeda, Koshi; Utsunomiya, Keita; Komemushi, Atsushi; Kanno, Shohei; Shiga, Toshiko; Tanigawa, Noboru

    2013-12-01

    Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.

  17. Nanoarchitectonics in cancer therapy and imaging diagnosis.

    PubMed

    Pandey, Abhijeet P; Girase, Nayandip M; Patil, Mahendra D; Patil, Pravin O; Patil, Dilip A; Deshmukh, Prashant K

    2014-01-01

    Nanoarchitectonics has gained remarkable importance due to the fabrication of various recent nanostructures with the capability of being used in biomedical science, particularly in cancer diagnosis and treatment. These nanosized structures possess unique physical and optical properties that can be exploited for cancer therapeutics, and so nanoarchitectonics is popularly known as nanomedicine. The goal of this review is to discuss the latest findings in nanostructures research including nanocrystals, nanotubes, nanoshells, nanopillars, nanoballs, nanoflowers, nanorods, nanocontainers, nanobelts, nanocages, nanodiscs, nanodots, nanoprisms, nanoplates, nanorings, nanocubes, nanobranches, nanospheres, nanorattles, nanostars, nanotrees, nanowires, nanowalls, nanodiamonds, nanosheets, layered nanostructures, quantum dots, mesoporous nanostructures etc. in the field of cancer therapy and imaging. This review further highlights brief information about use of radionuclide in cancer. Lastly, different nanoformulations that are available in the market or are under clinical trials for cancer therapy and imaging are discussed. PMID:24730301

  18. Nanoarchitectonics in cancer therapy and imaging diagnosis.

    PubMed

    Pandey, Abhijeet P; Girase, Nayandip M; Patil, Mahendra D; Patil, Pravin O; Patil, Dilip A; Deshmukh, Prashant K

    2014-01-01

    Nanoarchitectonics has gained remarkable importance due to the fabrication of various recent nanostructures with the capability of being used in biomedical science, particularly in cancer diagnosis and treatment. These nanosized structures possess unique physical and optical properties that can be exploited for cancer therapeutics, and so nanoarchitectonics is popularly known as nanomedicine. The goal of this review is to discuss the latest findings in nanostructures research including nanocrystals, nanotubes, nanoshells, nanopillars, nanoballs, nanoflowers, nanorods, nanocontainers, nanobelts, nanocages, nanodiscs, nanodots, nanoprisms, nanoplates, nanorings, nanocubes, nanobranches, nanospheres, nanorattles, nanostars, nanotrees, nanowires, nanowalls, nanodiamonds, nanosheets, layered nanostructures, quantum dots, mesoporous nanostructures etc. in the field of cancer therapy and imaging. This review further highlights brief information about use of radionuclide in cancer. Lastly, different nanoformulations that are available in the market or are under clinical trials for cancer therapy and imaging are discussed.

  19. Reactive oxygen species in redox cancer therapy.

    PubMed

    Tong, Lingying; Chuang, Chia-Chen; Wu, Shiyong; Zuo, Li

    2015-10-10

    The role of reactive oxygen species (ROS) in cancer cells has been intensively studied for the past two decades. Cancer cells mostly have higher basal ROS levels than their normal counterparts. The induction of ROS has been shown to be associated with cancer development, metastasis, progression, and survival. Various therapeutic approaches targeting intracellular ROS levels have yielded mixed results. As widely accepted dietary supplements, antioxidants demonstrate both ROS scavenging ability and anti-cancer characteristics. However, antioxidants may not always be safe to use since excessive intake of antioxidants could lead to serious health concerns. In this review, we have evaluated the production and scavenging systems of ROS in cells, as well as the beneficial and harmful roles of ROS in cancer cells. We also examine the effect of antioxidants in cancer treatment, the effect of combined treatment of antioxidants with traditional cancer therapies, and the side effects of excessive antioxidant intake.

  20. Fifty years of systemic therapy for breast cancer: from one size fits all to tailored therapy.

    PubMed

    Burstein, Harold J

    2014-01-01

    Breast cancer treatment has evolved dramatically in the past 50 years. In addition to innovations in medical therapy-including widespread use of endocrine treatments, chemotherapy, and anti-HER2 agents-medical advances in genetic testing, imaging, and screening have revolutionized care. As profound as these changes in medical treatment have been, however, they are matched by a cultural transformation in the way society understands, discusses, and cares about breast cancer. Breast cancer has evolved from an unnamed affliction to a disease that is regularly featured on the front page of the newspapers, and is discussed in countless forums in traditional and social media. Clinical specialization in breast cancer among oncologists has given patients access to dedicated specialists around the country. These transformations will be highlighted through the analysis of a patient, Rachel Carson, who died 50 years ago from breast cancer.

  1. Advances in cryoablation for pancreatic cancer

    PubMed Central

    Luo, Xiao-Mei; Niu, Li-Zhi; Chen, Ji-Bing; Xu, Ke-Cheng

    2016-01-01

    Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer. PMID:26811625

  2. Avoiding obsolescence in advanced prostate cancer management: a guide for urologists.

    PubMed

    Shore, Neal D; Karsh, Lawrence; Gomella, Leonard G; Keane, Thomas E; Concepcion, Raoul S; Crawford, E David

    2015-02-01

    Prostate cancer is one of the most common cancers diagnosed in men in the USA and 20–30% of men treated for localised prostate cancer will fail therapy and develop advanced prostate cancer. More drugs have been approved for the treatment of advanced prostate cancer in the past 3 years than in the past three decades, and each drug has its own mechanism of action and, often, unique monitoring requirements. As the treatment landscape for men with advanced prostate cancer is undergoing significant expansion, the roles of both oncologists and urologists are shifting, and the decision for the urologist to treat vs refer requires early assessment to identify which patients are candidates for these novel treatments and the monitoring of patients for tolerability, response, and potential side-effects. Given these rapid changes, the authors of this review met in January 2013 and again in April 2013 to discuss the current challenges facing urologists in adopting these new treatments into their own practices. Here, we provide a brief overview of advanced prostate cancer medical therapies approved in the past decade, the necessary monitoring procedures and early detection methods needed to safely and effectively manage patients receiving these therapies, and our recommendations for applying these new therapies within different models of urology practice, such that urologists can remain an integral component of their patient's care once he has transitioned into advanced prostate cancer

  3. Avoiding obsolescence in advanced prostate cancer management: a guide for urologists.

    PubMed

    Shore, Neal D; Karsh, Lawrence; Gomella, Leonard G; Keane, Thomas E; Concepcion, Raoul S; Crawford, E David

    2015-02-01

    Prostate cancer is one of the most common cancers diagnosed in men in the USA and 20–30% of men treated for localised prostate cancer will fail therapy and develop advanced prostate cancer. More drugs have been approved for the treatment of advanced prostate cancer in the past 3 years than in the past three decades, and each drug has its own mechanism of action and, often, unique monitoring requirements. As the treatment landscape for men with advanced prostate cancer is undergoing significant expansion, the roles of both oncologists and urologists are shifting, and the decision for the urologist to treat vs refer requires early assessment to identify which patients are candidates for these novel treatments and the monitoring of patients for tolerability, response, and potential side-effects. Given these rapid changes, the authors of this review met in January 2013 and again in April 2013 to discuss the current challenges facing urologists in adopting these new treatments into their own practices. Here, we provide a brief overview of advanced prostate cancer medical therapies approved in the past decade, the necessary monitoring procedures and early detection methods needed to safely and effectively manage patients receiving these therapies, and our recommendations for applying these new therapies within different models of urology practice, such that urologists can remain an integral component of their patient's care once he has transitioned into advanced prostate cancer PMID:25756134

  4. Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

    ClinicalTrials.gov

    2011-07-14

    Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

  5. Palbociclib for Advanced Breast Cancer

    Cancer.gov

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  6. Ganetespib radiosensitization for liver cancer therapy

    PubMed Central

    Chettiar, Sivarajan T.; Malek, Reem; Annadanam, Anvesh; Nugent, Katriana M.; Kato, Yoshinori; Wang, Hailun; Cades, Jessica A.; Taparra, Kekoa; Belcaid, Zineb; Ballew, Matthew; Manmiller, Sarah; Proia, David; Lim, Michael; Anders, Robert A.; Herman, Joseph M.; Tran, Phuoc T.

    2016-01-01

    ABSTRACT Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33–1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies. PMID:26980196

  7. The curability of advanced cancers with chemotherapy.

    PubMed

    Boh-Seng, Y

    1981-07-01

    The tremendous progress that has been made in the chemotherapy of malignant diseases since the early 1950's has enabled the cure of a significant number of cancers such as chloriocarcinoma, Burkitt's lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, the acute leukaemias, testicular carcinoma, and many childhood cancers such as rhabdomyosarcoma, Wilm's tumor, Ewing's sarcoma, ovarian cancer, and retinoblastoma. As a result, the mortality from cancers has dropped by 15% for persons under the age of 45 years and even more for those under 30 years of age. Many other metastatic cancers can now be successfully controlled with chemotherapy and, ultimately, more will be added to the growing list of curable cancers. The chemotherapeutic agents responsible for the cures of some cancers include asparaginase, actinomycin D, Adriamycin, bleomycin, cisplatin, cyclophosphamide, cytosine arabinoside, 5-fluorouracil, 6-mercaptopurine, methotrexate, nitrogen mustard, prednisone, procarbazine, and vincristine. The discovery of new effective drugs such as AMSA and anthracenedione promises to improve the success rates obtained with present therapy. Chemotherapy is indicated for every patient who has metastatic cancer, since virtually every patient can receive some palliation from such therapy, while for some patients chemotherapy holds the promise of prolongation of life or even cure.

  8. Advances in Stem Cell Therapy for Leukemia.

    PubMed

    Tian, Hong; Qu, Qi; Liu, Liming; Wu, Depei

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective post remission treatment for leukemia, resulting in lower relapse rates than alternative therapies. However, it is limited by the lack of suitable human leukocyte antigen (HLA) matched donors and high rates of transplant-related morbidity and mortality. Cord blood transplantation (CBT) and haploidentical SCT (haplo-SCT) expand the potential donor pool but are also associated with major complications. Co-infusion of third-party donor stem cells with a CBT/haplo-SCT, which is called "dual transplantation," has been reported to improve the outcome of HSCT by accelerating hematopoietic reconstitution and reducing the incidence of graft-versus-host disease (GVHD). In addition, infusion of HLA-mismatched donor granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells after chemotherapy, the so called "microtransplantation", has been shown to promote the graft-versus-leukemia effect and hasten hematopoietic recovery without amplifying GVHD. Herein, we review recent advances in stem cell therapy for leukemia with a specific focus on dual transplantation and microtransplantation.

  9. Impact of Incidental Irradiation on Clinically Uninvolved Nodal Regions in Patients With Advanced Non-Small-Cell Lung Cancer Treated With Involved-Field Radiation Therapy: Does Incidental Irradiation Contribute to the Low Incidence of Elective Nodal Failure?

    SciTech Connect

    Kimura, Tomoki; Togami, Taro; Nishiyama, Yoshihiro; Ohkawa, Motoomi; Takashima, Hitoshi

    2010-06-01

    Purpose: To evaluate the incidental irradiation dose to elective nodal regions in the treatment of advanced non-small-cell lung cancer with involved-field radiation therapy (IF-RT) and the pattern of elective nodal failure (ENF). Methods and Materials: Fifty patients with advanced non-small-cell lung cancer, who received IF-RT at Kagawa University were enrolled. To evaluate the dose of incidental irradiation, we delineated nodal regions with a Japanese map and the American Thoracic Society map (levels 1-11) in each patient retrospectively and calculated the dose parameters such as mean dose, D95, and V95 (40 Gy as the prescribed dose of elective nodal irradiation). Results: Using the Japanese map, the median mean dose was more than 40 Gy in most of the nodal regions, except at levels 1, 3, and 7. In particular, each dosimetric parameter of level 1 was significantly lower than those at other levels, and each dosimetric parameter of levels 10 to 11 ipsilateral (11I) was significantly higher than those in other nodal regions. Using the American Thoracic Society map, basically, the results were similar to those of the Japanese map. ENF was observed in 4 patients (8%), five nodal regions, and no mean dose to the nodal region exceeded 40 Gy. On the Japanese map, each parameter of these five nodal region was significantly lower than those of the other nodal regions. Conclusions: These results show that a high dose of incidental irradiation may contribute to the low incidence of ENF in patients who have received IF-RT.

  10. Planning analysis for locally advanced lung cancer: dosimetric and efficiency comparisons between intensity-modulated radiotherapy (IMRT), single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT)

    PubMed Central

    2011-01-01

    Purpose To analyze the differences between the intensity-modulated radiotherapy (IMRT), single/partial-arc volumetric modulated arc therapy (SA/PA-VMAT) techniques in treatment planning for locally advanced lung cancer. Materials and methods 12 patients were retrospectively studied. In each patient's case, several parameters were analyzed based on the dose-volume histograms (DVH) of the IMRT, SA/PA-VMAT plans respectively. Also, each plan was delivered to a phantom for time comparison. Results The SA-VMAT plans showed the superior target dose coverage, although the minimum/mean/maximum doses to the target were similar. For the total and contralateral lungs, the higher V5/10, lower V20/30 and mean lung dose (MLD) were observed in the SA/PA-VMAT plans (p < 0.05, respectively). The PA-VMAT technique improves the dose sparing (V20, V30 and MLD) of the controlateral lung more notably, comparing to those parameters of the IMRT and SA-VMAT plans respectively. The delivered monitor units (MUs) and treatment times were reduced significantly with VMAT plans, especially PA-VMAT plans (for MUs: mean 458.3 vs. 439.2 vs. 435.7 MUs, p < 0.05 and for treatment time: mean 13.7 vs. 10.6 vs. 6.4 minutes, p < 0.01). Conclusions The SA-VMAT technique achieves highly conformal dose distribution to the target. Comparing to the IMRT plans, the higher V5/10, lower V20/30 and MLD were observed in the total and contralateral lungs in the VMAT plans, especially in the PA-VMAT plans. The SA/PA-VMAT plans also reduced treatment time with more efficient dose delivering. But the clinical benefit of the VMAT technique for locally advanced lung cancer needs further investigations. PMID:22014217

  11. Adoptive Cellular Therapy (ACT) for Cancer Treatment.

    PubMed

    Yang, Fan; Jin, Hao; Wang, Jian; Sun, Qian; Yan, Cihui; Wei, Feng; Ren, Xiubao

    2016-01-01

    Adoptive cellular therapy (ACT) with various lymphocytes or antigen-presenting cells is one stone in the pillar of cancer immunotherapy, which relies on the tumor-specific T cell. The transfusion of bulk T-cell population into patients is an effective treatment for regression of cancer. In this chapter, we summarize the development of various strategies in ACT for cancer immunotherapy and discuss some of the latest progress and obstacles in technical, safety, and even regulatory aspects to translate these technologies to the clinic. ACT is becoming a potentially powerful approach to cancer treatment. Further experiments and clinical trials are needed to optimize this strategy.

  12. Estrogen therapy in gynecological cancer survivors.

    PubMed

    Guidozzi, F

    2013-12-01

    Treatment of gynecological cancer has significant impact on a woman's quality of life because it commonly includes removal of the uterus and ovaries, both being the core of a woman's femininity, whilst irradiation and chemotherapy, be they as primary therapy or when indicated as postoperative adjuvant therapy, will lead to ablation of ovarian function if the ovaries had not been removed. This will lead to an acute onset of menopausal symptoms, which may be more debilitating than those occurring as a result of natural aging, and of which hot flushes, night sweats, insomnia, mood swings, vaginal dryness, decreased libido, malaise and a general feeling of apathy are the most common. About 25% of gynecological cancers will occur in pre- and perimenopausal women, a large percentage of whom will become menopausal as a result of their treatment. There are also the gynecological cancer survivors who are not rendered menopausal as a result of the treatment strategy but who will become menopausal because of natural aging. Concern among the medical attendants of these women is whether use of estrogen therapy or estrogen and progestogens for their menopausal symptoms will reactivate tumor deposits and therefore increase the rate of recurrence and, as a result, decrease overall survival among these women. Yet the data that are available do not support this concern. There are eight retrospective studies and only one randomized study that have analyzed outcome in endometrial cancer survivors who used hormone therapy after their surgery, whilst, among ovarian cancer survivors, there are four retrospective studies and one randomized study. The studies do suffer from small numbers and, although the studies pertaining to endometrial cancer analyze mostly women with early-stage disease, a number of the studies in both the endometrial and ovarian cancer survivors do have a sizeable follow-up. These studies seem to support that estrogen therapy after the treatment for gynecological

  13. Bioengineering Strategies for Designing Targeted Cancer Therapies

    PubMed Central

    Wen, Xuejun

    2014-01-01

    The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

  14. Cancer survivorship: cardiotoxic therapy in the adult cancer patient; cardiac outcomes with recommendations for patient management.

    PubMed

    Steingart, Richard M; Yadav, Nandini; Manrique, Carlos; Carver, Joseph R; Liu, Jennifer

    2013-12-01

    Many types of cancer are now curable or, if not cured, becoming a chronic illness. In 2012, it was estimated that there were more than 13,500,000 cancer survivors in the United States. Late outcomes of these survivors are increasingly related to cardiovascular disease, either as a consequence of the direct effects of cancer therapy or its adverse effects on traditional cardiac risk factors (eg, obesity, hypertension, dyslipidemia, and diabetes mellitus). This article describes the therapies that have led to advances in cancer survival and the acute and chronic cardiovascular toxicities associated with these therapies. Recommendations are made for the surveillance and management of cancer survivors. Published guidelines on the subject of cardio-oncology are reviewed in light of clinical experience caring for these patients. To supplement this cancer-related knowledge base, appropriateness criteria and guidelines for cardiac care in the general population were extrapolated to cancer survivors. The result is a series of recommendations for surveillance and management of cardiovascular disease in cancer survivors. PMID:24331191

  15. Immune-based therapies for childhood cancer.

    PubMed

    Mackall, Crystal L; Merchant, Melinda S; Fry, Terry J

    2014-12-01

    After decades of research, immunotherapies for cancer are demonstrating increasing success. These agents can amplify existent antitumour immunity or induce durable antitumour immune responses in a wide array of cancers. The spectrum of immunotherapeutics is broad, spanning monoclonal antibodies and their derivatives, tumour vaccines, and adoptive therapies using T cells and natural killer cells. Only a small number of immunotherapies have been tested in paediatric cancers, but impressive antitumour effects have already been observed. Mononclonal antibodies targeting GD2 that induce antibody-dependent cell-mediated cytotoxicity improve survival in high-risk neuroblastoma. Bi-specific monoclonal antibodies that simultaneously target CD19 and activate T cells can induce remission in acute B-cell lymphoblastic leukaemia (B-ALL) and adoptive immunotherapy using T cells genetically engineered to express chimeric antigen receptors targeting CD19 induce impressive responses in B-ALL. Efforts are underway to generate and test new immunotherapies in a wider array of paediatric cancers. Major challenges include a need to identify immunotherapy targets on the most lethal childhood cancers, to expand availability of technology-intense platforms, such as adoptive cell therapy, to optimize management of novel toxicities associated with this new class of cancer therapies and to determine how best to incorporate these therapies into standard treatment paradigms.

  16. Gene Therapies for Cancer: Strategies, Challenges and Successes

    PubMed Central

    DAS, SWADESH K.; MENEZES, MITCHELL E.; BHATIA, SHILPA; WANG, XIANG-YANG; EMDAD, LUNI; SARKAR, DEVANAND; FISHER, PAUL B.

    2015-01-01

    Gene therapy, which involves replacement of a defective gene with a functional, healthy copy of that gene, is a potentially beneficial cancer treatment approach particularly over chemotherapy, which often lacks selectivity and can cause non-specific toxicity. Despite significant progress pre-clinically with respect to both enhanced targeting and expression in a tumor-selective manner several hurdles still prevent success in the clinic, including non-specific expression, low-efficiency delivery and biosafety. Various innovative genetic approaches are under development to reconstruct vectors/transgenes to make them safer and more effective. Utilizing cutting-edge delivery technologies, gene expression can now be targeted in a tissue- and organ-specific manner. With these advances, gene therapy is poised to become amenable for routine cancer therapy with potential to elevate this methodology as a first line therapy for neoplastic diseases. This review discusses recent advances in gene therapy and their impact on a pre-clinical and clinical level. PMID:25196387

  17. Targeted therapies in gastric cancer and future perspectives

    PubMed Central

    Yazici, Ozan; Sendur, M Ali Nahit; Ozdemir, Nuriye; Aksoy, Sercan

    2016-01-01

    Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed. PMID:26811601

  18. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

    PubMed

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

    Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

  19. [News and perspectives in the treatment of advanced gastric and colorectal cancers].

    PubMed

    Diciolla, A; Cristina, V; De Micheli, R; Digklia, A; Wagner, A D

    2015-05-20

    Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future.

  20. Advanced therapy medicinal products: current and future perspectives

    PubMed Central

    Hanna, Eve; Rémuzat, Cécile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Background Advanced therapy medicinal products (ATMPs) are innovative therapies that encompass gene therapy, somatic cell therapy, and tissue-engineered products. These therapies are expected to bring important health benefits, but also to substantially impact the pharmaceuticals budget. Objective The aim of this study was to characterise the ATMPs in development and discuss future implications in terms of market access. Methods Clinical trials were searched in the following databases: EudraCT (EU Drug Regulating Authorities Clinical Trials), ClinicalTrials.gov, and ICTRP (International Clinical Trials Registry Platform of the World Health Organization). Trials were classified by category of ATMP as defined by European regulation EC No. 1394/2007, as well as by development phase and disease area. Results The database search identified 939 clinical trials investigating ATMPs (85% ongoing, 15% completed). The majority of trials were in the early stages (Phase I, I/II: 64.3%, Phase II, II/III: 27.9%, Phase 3: 6.9%). Per category of ATMP, we identified 53.6% of trials for somatic cell therapies, 22.8% for tissue-engineered products, 22.4% for gene therapies, and 1.2% for combined products (incorporating a medical device). Disease areas included cancer (24.8%), cardiovascular diseases (19.4%), musculoskeletal (10.5%), immune system and inflammation (11.5%), neurology (9.1%), and others. Of the trials, 47.2% enrolled fewer than 25 patients. Due to the complexity and specificity of ATMPs, new clinical trial methodologies are being considered (e.g., small sample size, non-randomised trials, single-arm trials, surrogate endpoints, integrated protocols, and adaptive designs). Evidence generation post-launch will become unavoidable to address payers’ expectations. Conclusion ATMPs represent a fast-growing field of interest. Although most of the products are in an early development phase, the combined trial phase and the potential to cure severe chronic conditions suggest

  1. Biologic and immunologic therapy of ovarian cancer.

    PubMed

    Bookman, M A; Berek, J S

    1992-08-01

    Conventional cytotoxic chemotherapy fails to cure the majority of patients with advanced-stage ovarian cancer, in spite of encouraging initial antitumor responses. With the emergence of drug resistance in refractory tumors, new biologic and immunologic treatment strategies are needed. Small-volume residual peritoneal disease remains an attractive target for therapeutic trials; however, even in this optimal circumstance, few regimens have yet achieved a high frequency of pathologically confirmed complete remissions. Considerable progress has been made in understanding the impact of growth factors and their receptors on tumor growth regulation and modulation of response to chemotherapy. Better characterization of the antigens recognized by monoclonal antibodies, as well as sequencing of the antibodies themselves, has permitted the rational design of therapeutic reagents that take full advantage of molecular biology techniques for production and conjugation. Important limitations of preclinical models for prediction of host toxicity are recognized, and the reasons for treatment failure in situ, as well as strategies to prevent serious dose-limiting toxicities, are being explored. Further developments in cytokine biology, adoptive cellular therapy, monoclonal antibody conjugation, and molecular biology will continue to provide a growing array of reagents for critical evaluation.

  2. Gene therapy for cancer: regulatory considerations for approval

    PubMed Central

    Husain, S R; Han, J; Au, P; Shannon, K; Puri, R K

    2015-01-01

    The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells and the use of oncolytic viruses and bacteria have led to numerous clinical trials for cancer therapy, with several progressing to late-stage product development. At the time of this writing, no gene therapy product has been approved by the United States Food and Drug Administration (FDA). Some of the key scientific and regulatory issues include understanding of gene transfer vector biology, safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time. Because of the biological complexity of these products, the FDA encourages a flexible, data-driven approach for preclinical safety testing programs. The clinical trial design should be based on the unique features of gene therapy products, and should ensure the safety of enrolled subjects. This article focuses on regulatory considerations for gene therapy product development and also discusses guidance documents that have been published by the FDA. PMID:26584531

  3. Gene therapy for cancer: regulatory considerations for approval.

    PubMed

    Husain, S R; Han, J; Au, P; Shannon, K; Puri, R K

    2015-12-01

    The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells and the use of oncolytic viruses and bacteria have led to numerous clinical trials for cancer therapy, with several progressing to late-stage product development. At the time of this writing, no gene therapy product has been approved by the United States Food and Drug Administration (FDA). Some of the key scientific and regulatory issues include understanding of gene transfer vector biology, safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time. Because of the biological complexity of these products, the FDA encourages a flexible, data-driven approach for preclinical safety testing programs. The clinical trial design should be based on the unique features of gene therapy products, and should ensure the safety of enrolled subjects. This article focuses on regulatory considerations for gene therapy product development and also discusses guidance documents that have been published by the FDA.

  4. Advances in gastric cancer prevention.

    PubMed

    Giordano, Antonio; Cito, Letizia

    2012-09-10

    Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori (H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin (E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decision cannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled. PMID:23061031

  5. Role of radiation therapy in lung cancer management - a review.

    PubMed

    Shi, J-G; Shao, H-J; Jiang, F-E; Huang, Y-D

    2016-07-01

    Lung cancer is the leading cause of cancer death worldwide. Furthermore, more than 50% of lung cancer patients are found affected by distant metastases at the time of diagnosis. On the other hand, 20% of these patients are without regional spread and are good candidates for surgical operation. The remaining 30% represent an intermediate group whose tumors have metastasized up to regional lymph nodes. These remain 30% are the most appropriate candidates for radiation therapy. These patients are also called as "locally advanced lung cancer" or stage III lung cancer patients. In these patients strategy of combination therapy viz. radiation therapy in combination with chemotherapy is also tried by various groups in the recent past for this better management. However, long-term survival is still poor with a 5-year survival in 5-25% of patients. During the last decades, there has been a development in radiation strategies. The present review article focuses on different approaches to optimize radiotherapy for these patients. PMID:27466995

  6. [Systemic therapy of breast cancer: practice guideline].

    PubMed

    Horváth, Zsolt; Boér, Katalin; Dank, Magdolna; Kahán, Zsuzsanna; Kocsis, Judit; Kövér, Erika; Pajkos, Gábor; Pikó, Béla; Rubovszky, Gábor; Eckhardt, Sándor

    2016-09-01

    The article presents the practice guideline of systemic treatment of breast cancer and recommendations of the 3rd Hungarian Breast Cancer Consensus Conference. It reflects the recent international guidelines (ESMO, NCCN, ABC2, St Gallen's) irrespectively of the current financial opportunities. Here we follow the early - locally advanced - locally relapsed - metastatic breast cancer line for didactic considerations and we discuss the different subgroups of breast cancer based on hormone receptor and HER2 receptor status. Diagnosis and treatment options of rare clinical entities are summarised at the end of the paper. PMID:27579723

  7. Medullary Thyroid Cancer: Monitoring and Therapy

    PubMed Central

    Ball, Douglas W.

    2007-01-01

    This review summarizes clinical features and molecular pathogenesis of medullary thyroid cancer (MTC), and then focuses on current use of molecular, biochemical, and imaging disease markers as a basis for selection of appropriate therapy. Clinicians treating MTC patients face a series of challenges: 1) distinguishing MTC as early as possible from benign nodular disease and differentiated thyroid cancer (DTC) in order to choose appropriate initial surgery; 2) managing low-level residual cancer in otherwise asymptomatic individuals; and 3) treating progressive metastatic disease. Early clinical trials employing small molecules targeting Ret and/or VEGF receptors suggest that such approaches could be effective and well-tolerated. This review highlights early progress in targeted therapy of MTC, along with significant challenges in disease monitoring to appropriately select and evaluate patients being treated with these therapies. PMID:17673130

  8. Future of Bacterial Therapy of Cancer.

    PubMed

    Hoffman, Robert M

    2016-01-01

    Bacterial therapy of cancer has a centuries-long history and was first-line therapy at the hospital in New York City that would become Memorial Sloan-Kettering Cancer Center, under Dr. William B. Coley. However, after Coley's death in 1936, bacterial therapy of cancer ceased in the clinic until the present century. Clinical trials have been recently carried out for strains of the obligate anaerobe Clostridium novyi with the toxin gene deleted, and on an attenuated strain of Salmonella typhimurium (S. typhimurium), which is a facultative anaerobe that can grow in viable, as well as necrotic, areas of tumors, unlike Clostridium, which can only grow in the hypoxic areas. Our laboratory has developed the novel strain S. typhimurium A1-R that is effective against all tumor types in clinically-relevant mouse models, including patient-derived orthotopic xenograft (PDOX) mouse models. This chapter suggests future clinical applications for S. typhimurium A1-R.

  9. Induction therapy for lung cancer: sailing across the pillars of Hercules.

    PubMed

    Rocco, Gaetano; Morabito, Alessandro; Muto, Paolo

    2012-02-01

    In spite of numerous clinical trials, the jury is still out on the value of induction therapy for locally advanced lung cancer. We elected to address this topic from the multifaceted views of the clinicians often involved in lung cancer management and according the most recent views on locally advanced NSCLC. The concept of a prognostic stratification of N2 disease subsets, especially single vs multiple zone, has been introduced and this may lead to a new interpretation of locally advanced NSCLC. Ten crucial issues were identified that may have an impact on the approach to patients with locally advanced lung cancer in everyday practice.

  10. Strategies for advancing cancer nanomedicine

    NASA Astrophysics Data System (ADS)

    Chauhan, Vikash P.; Jain, Rakesh K.

    2013-11-01

    Cancer nanomedicines approved so far minimize toxicity, but their efficacy is often limited by physiological barriers posed by the tumour microenvironment. Here, we discuss how these barriers can be overcome through innovative nanomedicine design and through creative manipulation of the tumour microenvironment.

  11. Advanced endoscopic technologies for colorectal cancer screening

    PubMed Central

    Obstein, Keith L; Valdastri, Pietro

    2013-01-01

    Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621

  12. Novel Approaches in Anaplastic Thyroid Cancer Therapy

    PubMed Central

    Hsu, Kun-Tai; Yu, Xiao-Min; Audhya, Anjon W.; Jaume, Juan C.; Lloyd, Ricardo V.; Miyamoto, Shigeki; Prolla, Tomas A.

    2014-01-01

    Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future. PMID:25260367

  13. Targeted radionuclide therapies for pancreatic cancer.

    PubMed

    Shah, M; Da Silva, R; Gravekamp, C; Libutti, S K; Abraham, T; Dadachova, E

    2015-08-01

    Pancreatic malignancies, the fourth leading cause of cancer deaths, have an aggressive behavior with poor prognosis, resulting in a 5-year survival rate of only 4%. It is typically a silent malignancy until patients develop metastatic disease. Targeted radionuclide therapies of cancer such as radiolabeled peptides, which bind to the receptors overexpressed by cancer cells and radiolabeled antibodies to tumor-specific antigens provide a viable alternative to chemotherapy and external beam radiation of metastatic cancers. Multiple clinical trials of targeted radionuclide therapy of pancreatic cancer have been performed in the last decade and demonstrated safety and potential efficacy of radionuclide therapy for treatment of this formidable disease. Although a lot of progress has been made in treatment of pancreatic neuroendocrine tumors with radiolabeled (90)Y and (177)Lu somatostatin peptide analogs, pancreatic adenocarcinomas remain a major challenge. Novel approaches such as peptides and antibodies radiolabeled with alpha emitters, pre-targeting, bispecific antibodies and biological therapy based on the radioactive tumorlytic bacteria might offer a potential breakthrough in treatment of pancreatic adenocarcinomas.

  14. Targeting mitochondria metabolism for cancer therapy

    PubMed Central

    Weinberg, Samuel E; Chandel, Navdeep S

    2015-01-01

    Mitochondria have a well-recognized role in the production of ATP and the intermediates needed for macromolecule biosynthesis, such as nucleotides. Mitochondria also participate in the activation of signaling pathways. Overall, accumulating evidence now suggests that mitochondrial bioenergetics, biosynthesis and signaling are required for tumorigenesis. Thus, emerging studies have begun to demonstrate that mitochondrial metabolism is potentially a fruitful arena for cancer therapy. In this Perspective, we highlight recent developments in targeting mitochondrial meta