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AGS-003 to Be Tested With Sunitinib as RCC TreatmentA trial (NCT01582672) that will pair a targeted treatment with a vaccine therapy for firstline treatment of renal cell carcinoma (RCC) is recruiting at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute.
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ASCO 2016: Natural Killer Cell-Based Therapies in Blood CancersAs part of our coverage of the annual ASCO conference, we spoke with Dr. Veronika Bachanova on the role of NK cell therapy in hematologic malignancies.
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Adjuvant Therapy for Non-Small Cell Lung Cancer: Impact of Recent Clinical Trials on Community PracticeNon-small cell lung cancer (NSCLC) is diagnosed at an early stage, when it is amenable to surgical resection in approximately 20% to 25% of cases.
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Cytoreductive Nephrectomy, Immunotherapy-Based Systemic Therapy Induce Benefit in mRCCA pooled analysis compared survival among patients with metastatic renal cell carcinoma treated with cytoreductive nephrectomy and either targeted therapy or immunotherapy regimens utilizing checkpoint inhibitors.
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Should maintenance therapy serve as the standard of care in metastatic non-small-cell lung cancer?Patients with incurable NSCLC are less likely to progress to second-linetherapy with the right maintenance regimen. But maintenance therapyalso means committing patients to continuous treatment without anybreaks or chances to recover from adverse events.
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R-CHOP is standard of care for advanced DLBCL patientsRituximab (Rituxan) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard induction therapy for patients with advanced-stage diffuse large B-cell lymphoma, including both elderly and younger patients.
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Results of High-Dose Therapy and Autologous Stem Cell Transplant in Patients With Stage IV Hodgkin’s Disease: The Impact of Disease Status and Prior RadiotherapyAbout 20%-50% of patients with stage IV Hodgkin’s disease may suffer a relapse after initial chemotherapy-induced remission. Consolidative radiotherapy has been used in combination with chemotherapy to reduce relapse at areas of initial bulky disease; however, no survival benefit has been shown in the few randomized studies.
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Immune Recovery Appears Possible in AIDS PatientsGENEVA--Highly active antiretroviral therapy (HAART), usually including a protease inhibitor, can suppress human immunodeficiency virus (HIV) so much that the immune system actually begins to heal, according to work presented at the 12th World Conference on AIDS. In patients who respond well to HAART, CD4+ and CD8+ cell counts move toward normal, and the risk of opportunistic infections decreases (see Oncology News International, August, 1998, pp 1 and 20).
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Diagnostic Dilemma: GI DiseaseA 68-year-old man with a history of small-cell lung cancer with bony metastases was admitted with diarrhea. The patient had completed chemotherapy one week earlier with cisplatin and etoposide, along with radiation therapy, and irinotecan (Camptosar). The patient was found to be neutropenic.
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Hearing Loss in Pediatric Cancer Survivors Treated With CisplatinCisplatin is effective in treating several types of childhood cancers (eg, CNS tumors, osteosarcoma, hepatoblastoma, neuroblastoma, germ cell tumors). It is the most ototoxic drug used clinically, and hearing loss is a well-recognized toxicity of cisplatin therapy.
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Targeted Therapy for Metastatic Renal Cell Carcinoma: A Home Run or a Work in Progress?Recent advances in the understanding of the biology of renal cell carcinoma (RCC) have been translated into clinical treatment options in metastatic disease.
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Current Clinical Trials of Molecularly Targeted Agents in Children With Cancer, Part 2A number of molecularly targeted agents directed at critical cell survival and cell proliferation pathways have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while simultaneously diminishing acute and long-term toxic effects. Systematic evaluations of targeted agents are essential to achieving continued improvements in outcome for children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these and other agents in pediatric populations.
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Current Clinical Trials of Molecularly Targeted Agents in Children With Cancer, Part 2A number of molecularly targeted agents directed at critical cell survival and cell proliferation pathways have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while simultaneously diminishing acute and long-term toxic effects. Systematic evaluations of targeted agents are essential to achieving continued improvements in outcome for children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these and other agents in pediatric populations.
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Current Clinical Trials of Molecularly Targeted Agents in Children With Cancer, Part 2A number of molecularly targeted agents directed at critical cell survival and cell proliferation pathways have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while simultaneously diminishing acute and long-term toxic effects. Systematic evaluations of targeted agents are essential to achieving continued improvements in outcome for children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these and other agents in pediatric populations.
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Current Clinical Trials of Molecularly Targeted Agents in Children With Cancer, Part 2A number of molecularly targeted agents directed at critical cell survival and cell proliferation pathways have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while simultaneously diminishing acute and long-term toxic effects. Systematic evaluations of targeted agents are essential to achieving continued improvements in outcome for children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these and other agents in pediatric populations.
Latest:
Current Clinical Trials of Molecularly Targeted Agents in Children With Cancer, Part 2A number of molecularly targeted agents directed at critical cell survival and cell proliferation pathways have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while simultaneously diminishing acute and long-term toxic effects. Systematic evaluations of targeted agents are essential to achieving continued improvements in outcome for children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these and other agents in pediatric populations.
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Locally Advanced, Unresectable Non–Small-Cell Lung CancerA significant proportion of patients with non-small cell lung cancer (NSCLC) present with locally advanced, unresectable disease. For the most part, fit patients with this diagnosis are treated with combined-modality therapy. Relatively few are rendered resectable. Over the past two decades, combination chemotherapy and radiation, preferably concurrent chemoradiation, has emerged as the standard of care. However, survival gains have been offset, to some extent, by local, normal-tissue, in-field toxicity, particularly esophagitis and pneumonitis.
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Targeted Therapy in Squamous Cell Cancers of the Head and NeckThe 5-year survival of patients with locally advanced squamous cell cancers of the head and neck is still less than 30%. Treatment of these cancers involves significant functional impairment, diminished quality of life, and considerable time and expense. Local recurrence and distant metastases are still fairly common, and the development of second primary cancers has a significant impact on survival in patients with initial early-stage disease. Despite the success of combination chemoradiation in locally advanced head and neck cancers, these facts stress the need for improved treatment of this disease.
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Cancer Management Chapter 20: Melanoma and other skin cancersSkin cancer is the single most common form of cancer, accounting for more than 75% of all cancer diagnoses. More than 1 million cases of squamous cell and basal cell carcinomas are diagnosed annually, with a lifetime risk of more than one in five. The vast majority of skin cancers can be cured with surgery alone. Resection is the mainstay of therapy, even for skin cancer involving regional lymph nodes or, in some cases, more distant metastatic sites.
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BMT for Severe Autoimmune Diseases: An Idea Whose Time Has ComeStudies of hematopoietic stem-cell transplantation as a treatment for severe autoimmune diseases (SADS) are currently in progress. Dr. Burt thoroughly reviews the rationale for these studies. It includes: (1) preclinical studies showing that marrow transplantation is an effective therapy in animal models of autoimmune disease; (2) observations of the effect of stem-cell grafts on SADS in patients transplanted for other indications; and (3) improvements in the safety of the transplant procedure.
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Multidisciplinary Approach to Potentially Curable Non-Small Cell Carcinoma of the LungIn recent years, the treatment of many patients with non-small-cell lung cancer (NSCLC) has evolved into a multidisciplinary effort combining the talents of medical oncologists, radiation oncologists, and thoracic surgeons. Prospective, randomized trials have demonstrated improved survival rates in patients with locally advanced disease who are treated with cisplatin (Platinol)-based induction chemotherapy prior to radiation therapy[1,2] or surgery.[3,4] However, interpretation of these and other studies and application of the findings to the management of an individual patient require a thorough understanding of prognostic factors and staging.
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BRAF inhibition may enhance immunotherapy in melanomaA preclinical study provides the rationale for combining BRAF-targeted therapy with immunotherapy agents in patients with BRAF mutations. These mutations activate the MAPK signaling pathway, which leads to increased oncogenic potential. The researchers showed that in BRAF-mutant melanoma cell lines, a selective BRAF inhibitor (PLX4720) blocked the MAPK pathway and increased tumor antigen expression without affecting T-cell function.
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Commentary (Slavin): Nonmyeloablative Preparative Regimens for Allogeneic Hematopoietic TransplantationChamplin and colleagues haveelegantly summarized the conceptof nonmyeloablativestem cell transplantation (NST),stressing the importance of this newlyemerging procedure for the treatmentof patients with life-threateningmalignant hematologic and nonhematologicdiseases. This review doesnot include a description of the safetyand efficacy of NST for the treatmentof many life-threateningnonmalignant diseases for which noalternative therapy exists. This categoryencompasses a long list of geneticdisorders, diseases caused by adeficiency of stem cell products, andsyndromes associated with immunedeficiency. However, discussion ofthese illnesses is beyond the scopeof this review, which focuses oncancer.
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Hematopoietic Stem Cell Transplantation for Non-Hodgkin’s LymphomaHigh-dose myeloablative therapy with autologous or allogeneicstem cell rescue is an effective treatment strategy for non-Hodgkin’slymphoma (NHL), but NHL is much less likely to stay in remission afteran autologous transplant than after an allogeneic transplant. Thebenefit of undergoing an autologous transplant earlier in the course ofthe disease, especially for patients who present with intermediate orhigh scores on the International Prognostic Index of risk factors, is stillunclear. The addition of immunotherapy, biologic modifiers, andantibody therapy such as rituximab (Rituxan) or radiolabeled antibodyto the autologous transplant are approaches undergoing evaluation.Historically, there has been a high regimen-related mortality rateassociated with myeloablative allogeneic transplant that has made thisapproach a less appealing option for therapy. The use of nonmyeloablativeallogeneic transplants as treatment for NHL is less well studiedand remains to be defined.
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New Questions About Transplantation in Multiple MyelomaMultiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions—for example, tandem autologous transplants—we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.
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New Questions About Transplantation in Multiple Myeloma: Review 1Multiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions—for example, tandem autologous transplants—we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.
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New Questions About Transplantation in Multiple Myeloma: Review 2Multiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions—for example, tandem autologous transplants—we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.
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New Questions About Transplantation in Multiple Myeloma: Review 2Multiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions—for example, tandem autologous transplants—we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.
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Further Thoughts on a Rare EntityPrimary neuroendocrine neoplasms of the lung represent a clinical spectrum of tumors ranging from the relatively benign and slow-growing typical carcinoid to the highly aggressive small-cell lung carcinoma. The rarity of carcinoids has made the role of radiation therapy in their management controversial. This review considers the results of published studies to generate treatment recommendations and identify areas for future research. Surgery remains the standard of care for medically operable disease. Histology plays the most important role in determining the role of adjuvant radiation. Resected typical carcinoids likely do not require adjuvant therapy irrespective of nodal status. Resected atypical carcinoids and large-cell neuroendocrine carcinomas have a significant risk of local failure, for which adjuvant radiation likely improves local control. Definitive radiation is warranted in unresectable disease. Palliative radiation for symptomatic lesions has demonstrated efficacy for all histologies. Collaborative group trials are warranted.
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Pulmonary Carcinoid Tumors: The Need for Tailored AssessmentPrimary neuroendocrine neoplasms of the lung represent a clinical spectrum of tumors ranging from the relatively benign and slow-growing typical carcinoid to the highly aggressive small-cell lung carcinoma. The rarity of carcinoids has made the role of radiation therapy in their management controversial. This review considers the results of published studies to generate treatment recommendations and identify areas for future research. Surgery remains the standard of care for medically operable disease. Histology plays the most important role in determining the role of adjuvant radiation. Resected typical carcinoids likely do not require adjuvant therapy irrespective of nodal status. Resected atypical carcinoids and large-cell neuroendocrine carcinomas have a significant risk of local failure, for which adjuvant radiation likely improves local control. Definitive radiation is warranted in unresectable disease. Palliative radiation for symptomatic lesions has demonstrated efficacy for all histologies. Collaborative group trials are warranted.
