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Radiation for Chemo-Sensitization: A Phase II Trial of Cetuximab and Docetaxel With Low-Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck CarcinomaThis study evaluates low dose radiotherapy in combination with docetaxel and cetuximab in patients with recurrent, unresectable squamous cell carcinoma of the head and neck initially treated with definitive chemo-radiation therapy.
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Radiation for Chemo-Sensitization: A Phase II Trial of Cetuximab and Docetaxel With Low-Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck CarcinomaThis study evaluates low dose radiotherapy in combination with docetaxel and cetuximab in patients with recurrent, unresectable squamous cell carcinoma of the head and neck initially treated with definitive chemo-radiation therapy.
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Radiation for Chemo-Sensitization: A Phase II Trial of Cetuximab and Docetaxel With Low-Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck CarcinomaThis study evaluates low dose radiotherapy in combination with docetaxel and cetuximab in patients with recurrent, unresectable squamous cell carcinoma of the head and neck initially treated with definitive chemo-radiation therapy.
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Radiation for Chemo-Sensitization: A Phase II Trial of Cetuximab and Docetaxel With Low-Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck CarcinomaThis study evaluates low dose radiotherapy in combination with docetaxel and cetuximab in patients with recurrent, unresectable squamous cell carcinoma of the head and neck initially treated with definitive chemo-radiation therapy.
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Radiation for Chemo-Sensitization: A Phase II Trial of Cetuximab and Docetaxel With Low-Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck CarcinomaThis study evaluates low dose radiotherapy in combination with docetaxel and cetuximab in patients with recurrent, unresectable squamous cell carcinoma of the head and neck initially treated with definitive chemo-radiation therapy.
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Investigators Seek Expanded Use of Checkpoint Inhibitors in RCCIn contrast to the wide array of available therapies in the metastatic setting of renal cell carcinoma, in patients with localized disease, the results of trials investigating adjuvant systemic therapy after nephrectomy have so far been underwhelming.
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Dendritic Cell Vaccines Offer Promising Signals as Glioblastoma TherapyImmunotherapy is rapidly emerging as a very attractive and novel therapeutic approach for cancer, including for glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults.
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Optimizing the Duration of Trastuzumab: A Fresh PerspectiveABSTRACT Prior to the introduction of trastuzumab, the first targeted anti-HER2 agent, in 1998, patients diagnosed with HER2-positive breast cancer felt like they were being handed a death sentence. Despite treatment with aggressive chemotherapy, their tumors recurred faster, more often spread to brain and liver, and were associated with higher rates of death than HER2-negative tumors. However, in the 1980s, cancer researchers and oncologists recognized that HER2 could be targeted by a small molecule that binds to the receptor on the cell surface and blocks the signal telling the cell to divide. This small molecule was called trastuzumab, and it eventually completely changed how HER2-positive breast cancer was treated. The drug was first approved in the metastatic setting, and then the results of 2 pivotal randomized control trials demonstrated that the administration of trastuzumab in the adjuvant setting decreased the risk of breast cancer recurrence by 50%. These trials showed trastuzumab to be unequivocally effective in the adjuvant setting and the HERA trial results led to the adoption of 1 year of adjuvant trastuzumab as the standard of care. Since that time, the field of anti–HER2-targeted therapy has exploded, with the development of multiple targeted agents for use in the advanced and up-front settings. Although trastuzumab significantly improves outcomes for women diagnosed with HER2-positive breast cancer and has few adverse effects (AEs), the disadvantages are that it requires intravenous administration every 3 weeks and can be associated with cardiac AEs. It is also expensive. Given all of these factors, the question of whether a duration of trastuzumab that is shorter than 1 year may be acceptable for some patients with early-stage HER2-positive breast cancer is an important and very relevant one. Here, we will review the studies that have examined this question and evaluate their results.
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Optimizing the Duration of Trastuzumab: A Fresh PerspectiveABSTRACT Prior to the introduction of trastuzumab, the first targeted anti-HER2 agent, in 1998, patients diagnosed with HER2-positive breast cancer felt like they were being handed a death sentence. Despite treatment with aggressive chemotherapy, their tumors recurred faster, more often spread to brain and liver, and were associated with higher rates of death than HER2-negative tumors. However, in the 1980s, cancer researchers and oncologists recognized that HER2 could be targeted by a small molecule that binds to the receptor on the cell surface and blocks the signal telling the cell to divide. This small molecule was called trastuzumab, and it eventually completely changed how HER2-positive breast cancer was treated. The drug was first approved in the metastatic setting, and then the results of 2 pivotal randomized control trials demonstrated that the administration of trastuzumab in the adjuvant setting decreased the risk of breast cancer recurrence by 50%. These trials showed trastuzumab to be unequivocally effective in the adjuvant setting and the HERA trial results led to the adoption of 1 year of adjuvant trastuzumab as the standard of care. Since that time, the field of anti–HER2-targeted therapy has exploded, with the development of multiple targeted agents for use in the advanced and up-front settings. Although trastuzumab significantly improves outcomes for women diagnosed with HER2-positive breast cancer and has few adverse effects (AEs), the disadvantages are that it requires intravenous administration every 3 weeks and can be associated with cardiac AEs. It is also expensive. Given all of these factors, the question of whether a duration of trastuzumab that is shorter than 1 year may be acceptable for some patients with early-stage HER2-positive breast cancer is an important and very relevant one. Here, we will review the studies that have examined this question and evaluate their results.
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Immunotherapy in Advanced Lung CancerABSTRACT Historically, platinum-based chemotherapy was the standard of care for metastatic lung cancer. However, since the success of immune checkpoint inhibitors (ICIs) in melanoma, PD-1/PD-L1 and CTLA-4 immune checkpoint pathways have been established as effective therapies to manage advanced non–small cell lung cancer (NSCLC) and extensive-stage (ES) small cell lung cancer (SCLC). Multiple large-scale randomized clinical trials have analyzed the effects of ICIs in NSCLC, and results of these trials have since translated to the approval of single-agent PD-1/PD-L1 inhibitors, and the combination of PD-1 inhibitors with platinum-based chemotherapy has become the new standard of care for patients with advanced NSCLC. Furthermore, in ES SCLC, in which chemotherapy or chemoradiation has been the standard of care for decades, 2 anti–PD-1/PD-L1 agents have been approved for use in the frontline setting for ES SCLC, in combination with chemotherapy. Despite progressive integration of immunotherapy into treatment regimens, there remains a need for reliable biomarkers to precisely determine therapy candidates.
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In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHLContamination of the peripheral blood stem-cell (PBSC) graft with lymphoma and residual disease remaining in the patient after high-dose therapy are two potential causes of relapse after autologous transplantation. Using a tumor-specific monoclonal antibody may be one way to purge the stem-cell graft in vivo and increase the efficacy of the preparative regimen. Rituximab (Rituxan) is an IgG1 kappa chimeric mouse/human antibody containing murine light- and heavy-chain variable regions and human gamma 1 heavy-chain and light-chain constant regions. The antibody reacts specifically with the CD20 antigen found on the surface of malignant and normal B-cells.
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The Addition of Rituximab to Combination Chemotherapy With Fludarabine, Cyclophosphamide, Mitoxantrone-Results of a Prospective Randomized Comparison by the German Low Grade Study GroupRituximab (Rituxan) has shown high activity in relapsed follicular lymphomas when given alone, and phase II studies indicate that its addition to chemotherapy may further improve response rates substantially. Because prospective randomized studies have not been available so far, the German Low Grade Study Group (GLSG) started a multicenter national trial in patients with relapsed or refractory follicular cell lymphoma (FCL) or mantle cell lymphoma (MCL). As patients were treated for first-line therapy with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone), the FCM (fludarabine [Fludara], cyclophosphamide, mitoxantrone [Novantrone]) combination was chosen for salvage chemotherapy.
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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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Cutaneous Side Effects of Multikinase Inhibitors Used in Renal Cell CancerParalleling the increasing use of multikinase inhibitors in the field of cancer therapy, patients and clinicians are confronted with frequently occurring cutaneous side effects associated with the use of these new drugs. Two such targeted agents, sunitinib (Sutent) and sorafenib (Nexavar), were recently approved by the US Food and Drug Administration to treat patients with metastatic renal cell cancer (RCC).
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Metastatic RCC: Moving Towards a Chronic DiseaseThe article by Posadas and Figlin on systemic therapy in advanced renal cell carcinoma (RCC) provides a very interesting and comprehensive review of our current knowledge concerning the treatment of RCC.
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Treatment of Acute Myelogenous LeukemiaThere have been significant advances in our understanding of the biology of acute myelogenous leukemia (AML), and to a lesser extent, in its treatment. Dr. Estey has provided an excellent overview of the current state of the clinical management of the disease. He has described both the standard therapeutic approaches, including allogeneic hematopoietic stem cell transplantation, as well as the role of investigational therapy. The present state of clinical research in AML is reviewed in some detail in the context of the broad clinical investigation of the disease at the M. D. Anderson Cancer Center. Dr. Estey makes a strong argument for the early consideration of investigational therapy, focusing on patients for whom "standard" therapy is demonstrably inadequate.
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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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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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Hematopoietic Stem Cell Transplantation in the Elderly: More Questions Than AnswersHematopoietic stem cell (HSC) transplantation may improve outcomes of patients with hematologic malignancies not curable with conventional therapies. In some clinical settings, transplantation represents the only curative option. The feasibility and efficacy of this approach in older patients are undefined, since this population has been excluded from nearly all clinical trials. Advances in supportive care, HSC harvesting, and safer conditioning regimens have made this therapy available to patients well into their 6th and 7th decades of life. Recent evidence suggests that elderly patients with good performance status and no comorbidities could, in fact, not only survive the transplant with reasonable risk, but also benefit in the same measure as younger patients.
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Evolving Role of Stem Cell Transplant in the ElderlyHematopoietic stem cell (HSC) transplantation may improve outcomes of patients with hematologic malignancies not curable with conventional therapies. In some clinical settings, transplantation represents the only curative option. The feasibility and efficacy of this approach in older patients are undefined, since this population has been excluded from nearly all clinical trials. Advances in supportive care, HSC harvesting, and safer conditioning regimens have made this therapy available to patients well into their 6th and 7th decades of life. Recent evidence suggests that elderly patients with good performance status and no comorbidities could, in fact, not only survive the transplant with reasonable risk, but also benefit in the same measure as younger patients.
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Is There a Role for Dose-Intensive Chemotherapy With Stem Cell Rescue in Breast Cancer?During the 1990s, perhaps no other therapy for women with breast cancer was more controversial than high-dose chemotherapy with autologous bone marrow and/or peripheral stem cell support. With encouraging results from late phase I and early phase II trials in the early to mid-1990s, high-dose chemotherapy was promoted by its many enthusiastic proponents as a potentially great leap forward for women with high-risk, node-positive or metastatic disease.
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Evolution of Combined Modality Therapy for Stage III Non–Small-Cell Lung CancerA number of randomized clinical trials and meta-analyses now support the conclusion that combined modality regimens that include cisplatin (Platinol)-based chemotherapy improve survival in stage III non–small-cell lung
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Evolution of Combined Modality Therapy for Stage III Non–Small-Cell Lung CancerA number of randomized clinical trials and meta-analyses now support the conclusion that combined modality regimens that include cisplatin (Platinol)-based chemotherapy improve survival in stage III non–small-cell lung
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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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Gemcitabine/Cisplatin as Induction Therapy for Stage IIIA N2 Non–Small-Cell Lung CancerBecause the majority of patients with stage IIIA N2 non–small-cell lung cancer (NSCLC) ultimately die of distant metastases, recent efforts to improve their intermediate- and long-term survival have focused on neoadjuvant
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Evolution of Combined Modality Therapy for Stage III Non–Small-Cell Lung CancerA number of randomized clinical trials and meta-analyses now support the conclusion that combined modality regimens that include cisplatin (Platinol)-based chemotherapy improve survival in stage III non–small-cell lung
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Current Role of Irinotecan in the Treatment of Non-Small-Cell Lung CancerLung cancer remains the primary cause of cancer-related death in both men and women in the United States. Chemotherapy has been shown to provide a survival benefit in patients with advanced non-small-cell lung cancer (NSCLC), and current regimens have produced median survivals of approximately 8 months and 1-year survival rates of 30% to 35% in patients with stage IIIB and IV disease. Nevertheless, there remains room for improvement. Irinotecan (CPT-11, Camptosar) has demonstrated efficacy in the treatment of small-cell lung cancer (SCLC). It also appears to have promising activity in advanced NSCLC, producing overall response rates of up to 32%. Combinations of irinotecan and cisplatin or carboplatin (Paraplatin) have resulted in overall response rates of 25% to 56% in phase II and III studies in patients with advanced disease, with median survivals ranging from 9 to 13 months and 1-year survival rates of 33% to 58%. Current irinotecan-based doublet and triplet regimens appear to produce promising response rates with manageable toxicities. In addition, irinotecan has demonstrated potential as a radiosensitizing agent and is currently being evaluated in several trials of combined-modality therapy in patients with locally advanced NSCLC. Early trials of irinotecan in combination with cisplatin or carboplatin along with radiation therapy have reported overall response rates of 60% to 67%. The approach appears to have potential and warrants further study. [ONCOLOGY 16:1153-1168, 2002]
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Paclitaxel and Carboplatin With Thoracic Radiation: Locally Advanced Non–Small-Cell Lung CancerCombined-modality approaches integrating carboplatin (Paraplatin) and low doses of weekly paclitaxel (Taxol) with thoracic radiation therapy for prolonging survival in patients with locally advanced non–small-cell lung cancer
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Radiation Therapy in the Management of Brain Metastases From Renal Cell CarcinomaBrain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.
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Concomitant Cisplatin, Vinorelbine, and Radiation in Advanced Chest MalignanciesNewer chemotherapy drugs have shown encouraging activity in advanced non-small-cell lung cancer. Based on these improved outcomes, as well as the high rate of distant relapse in patients with locally advanced disease, several recent studies have evaluated the use of systemic therapy in patients with earlier-stage disease.
