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Diagnosis and Management of Mycosis FungoidesMycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly symptomatic progressive skin lesions, including patches, plaques, tumors, and erytheroderma, and has a poorer prognosis at later stages. Diagnosis remains difficult owing to MF’s nonspecific skin presentation and identification of the optimal treatment strategy is challenging given the paucity of controlled trials and numerous and emerging treatment options. Management includes topical therapy with the addition of systemic therapy for patients with later-stage disease including tumors; erythroderma; and nodal, visceral, or blood involvement. Topical therapies include mechlorethamine (nitrogen mustard), carmustine (BCNU), steroids, bexarotene gel (Targretin Gel), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy. Systemic therapies include interferon, retinoids, oral bexarotene (Targretin), denileukin diftitox (Ontak), vorinostat (Zolinza), extracorporeal photochemotherapy (photopheresis), and cytotoxic chemotherapy. Herein, we outline clinically relevant aspects of MF, including clinical presentation, pathology, diagnosis, and staging. We describe in detail existing and emerging therapeutics and offer specific recommendations for management of each stage of MF.
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PORTable Indications in Non–Small-Cell Lung CarcinomaDrs. Kelsey, Marks, and Wilson open their excellent review article by asking “Where do we stand?” with respect to postoperative radiation therapy (PORT) for non–small-cell lung cancer (NSCLC).[1] Frankly, PORT has not exactly been standing tall for the past decade-leaning, crouching, or perhaps squatting might be a better verb.
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Are We Approaching a Fourth Generation of Therapies for Metastatic Kidney Cancer?Drs. Rini and Bukowski do an excellent job of updating and commenting on the rapidly evolving field of therapy for metastatic renal cell carcinoma (RCC).
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An Odd But Synergistic Couple: Immunotherapy Combined With RadiotherapyRadiation therapy (RT) and immunotherapy of cancer both date back more than 100 years, and yet, because radiation was often considered immunosuppressive, there had been little enthusiasm for combining them until recently. Immunotherapy has an established role in the treatment of some cancers-superficial bladder cancer treated with bacillus Calmette-Guérin (BCG), renal cell carcinoma and melanoma treated with interferon and interluekin (IL)-2 (Proleukin), and breast cancer and lymphoma treated with monoclonal antibodies such as trastuzumab (Herceptin) and rituximab (Rituxan), which partly function through antibody-dependent cellular cytotoxicity.
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An Odd But Synergistic Couple: Immunotherapy Combined With RadiotherapyRadiation therapy (RT) and immunotherapy of cancer both date back more than 100 years, and yet, because radiation was often considered immunosuppressive, there had been little enthusiasm for combining them until recently. Immunotherapy has an established role in the treatment of some cancers-superficial bladder cancer treated with bacillus Calmette-Guérin (BCG), renal cell carcinoma and melanoma treated with interferon and interluekin (IL)-2 (Proleukin), and breast cancer and lymphoma treated with monoclonal antibodies such as trastuzumab (Herceptin) and rituximab (Rituxan), which partly function through antibody-dependent cellular cytotoxicity.
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Radiation Therapy Options in Small-Cell Lung CancerThis video reviews options for radiation therapy in the treatment of small-cell lung cancer, including dosing frequency and use of thoracic and cranial irradiation in extensive-stage disease.
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Something Old, Something New: Options for Treating Relapsed Mantle Cell LymphomaDr. Ruan and colleagues provide an excellent summary of available treatment options, as well as new drugs on the horizon, for the management of relapsed mantle cell lymphoma (MCL). As the authors emphasize, treatment of relapsed MCL is strongly influenced by the patient’s first-line therapy and needs to be individualized based on both patient and disease characteristics.
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Something Old, Something New: Options for Treating Relapsed Mantle Cell LymphomaDr. Ruan and colleagues provide an excellent summary of available treatment options, as well as new drugs on the horizon, for the management of relapsed mantle cell lymphoma (MCL). As the authors emphasize, treatment of relapsed MCL is strongly influenced by the patient’s first-line therapy and needs to be individualized based on both patient and disease characteristics.
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The Future of NSCLC: Molecular Profiles Guiding Treatment DecisionsThe authors of "ALK-Targeted Therapy for Lung Cancer: Ready for Prime Time," in this issue of ONCOLOGY, address the newest developments in the field of targeted therapies for advanced non–small-cell lung cancer (NSCLC).
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Radioimmunotherapy: An Underutilized AlternativeTositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.
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Building on the Promise of RadioimmunotherapyTositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.
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The Future of Immunotherapy in Prostate CancerThere has been a resurgence of interest in developing noncytotoxic immune therapies for patients with either hormone-naive biochemically relapsed post-primary therapy or castrate metastatic prostate cancer. The rationale for developing an immunotherapeutic approach has been based on the overexpression and underglycosylation of a wide variety of altered "self" molecules including prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as targets for immune recognition and attack. In addition, such a strategy could theoretically make use of the patient's immune system to fight the tumor particularly if their disease is of reasonably low volume. A variety of immunotherapeutic approaches have been explored through phase I, II, and now phase III trials demonstrating that immunologic tolerance could be broken, as evidenced by the development of high-titer antibodies and T-cell responses specific for the tumor. What appears to be revolutionizing the immunotherapy field is the combination of vaccines with cytokines or immune modulators, which not only potentiate immune reactivity in vivo but foster dramatic antitumor responses. This review explores the challenges now faced in establishing a role for immune therapies for prostate cancer treatment.
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Managing the Patient With Borderline Resectable Lung CancerDespite recent therapeutic advances, lung cancer continues to be one of the leading causes of cancer-related mortality. Of the various histologic subtypes, non–small-cell lung cancer (NSCLC) is the most common-accounting for approximately 85% of all lung cancers-and will be the focus of this article. In general, the treatment of lung cancer may include surgery, radiation therapy, systemic therapy (eg, chemotherapy with or without targeted therapy), or a combination of the above. Surgery continues to offer the best chance of long-term cure. The initial treatment of stage I and II NSCLC usually entails surgical resection, whereas stage IV disease is primarily treated with systemic agents, in light of the lack of curative potential with surgery and/or radiation therapy alone. It is locally advanced NSCLC, including stage IIIA and IIIB disease, that continues to pose a therapeutic dilemma, given its heterogeneous nature.
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Wealth of Riches in RCC Treatment: How Do We Avoid 'Devaluing the Dollar'?The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.
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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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Commentary on Abstract #1890In medically suitable patients with stage III (locally advanced) non–small-cell lung cancer, the use of cisplatin (Platinol)-based chemotherapy as induction therapy prior to definitive local therapy has been shown to improve survival (J Natl Cancer Inst 86:673-680, 1994; Ann Intern Med 125:723-729, 1996). This is true regardless of whether the local treatment modality used is surgery or thoracic irradiation. However, because cisplatin therapy is particularly toxic, there is interest in studying other agents in the induction setting. Given its activity in non–small-cell lung cancer, docetaxel (Taxotere) is one logical agent to investigate.
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Do Oncogenic Drivers Exist in Squamous Cell Carcinoma of the Lung?The Cancer Genome Atlas provides us with our first thorough insight into the genetic heterogeneity of squamous cell carcinoma of the lung; whether these findings will translate into personalized squamous cell lung cancer therapy is yet to be determined.
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Do Oncogenic Drivers Exist in Squamous Cell Carcinoma of the Lung?The Cancer Genome Atlas provides us with our first thorough insight into the genetic heterogeneity of squamous cell carcinoma of the lung; whether these findings will translate into personalized squamous cell lung cancer therapy is yet to be determined.
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Do Oncogenic Drivers Exist in Squamous Cell Carcinoma of the Lung?The Cancer Genome Atlas provides us with our first thorough insight into the genetic heterogeneity of squamous cell carcinoma of the lung; whether these findings will translate into personalized squamous cell lung cancer therapy is yet to be determined.
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Management of a Patient With Stage IIIA (N2) NSCLCThe appropriate treatment of patients with stage IIIA (N2) non–small-cell lung cancer (NSCLC) is unclear. With this case report and review, we address the history, assessment, and management of a 67-year-old patient with this diagnosis, and then discuss the challenges in managing N2 disease, as well as the roles of systemic therapy, surgery, and postoperative radiation therapy.
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Older multiple myeloma patients show active response to novel agentsFully 88% of older adults with newly diagnosed multiple myeloma have at least a very good partial response when treated with low-dose autologous stem cell transplantation that is preceded by bortezomib-containing induction therapy and followed by lenalidomide-containing consolidation and maintenance therapy, according to trial results from the University of Turin in Italy.
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Histologic Subtype in NSCLC: Does It Matter?Since the publication of a meta-analysis in 1995 that demonstrated a modest survival benefit compared to best supportive care, platinum-based chemotherapy became the cornerstone of therapy in the first-line setting in advanced-stage non–small-cell lung cancer (NSCLC) for patients with good performance status.[1] A recent meta-analysis of 16 randomized trials including 2,714 patients demonstrated an advantage of chemotherapy over best supportive care with an absolute improvement in survival of 9% at 12 months.[2]
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Doublet Chemo Proves Superior to Single-agent Therapy in Older Patients with Advanced Non-small-cell Lung CancerData from French trial should inform treatment decisions in the majority of lung cancer patients aged 70 and up.
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Toxicities in RTOG Combined-Modality Trials for Inoperable Non–Small-Cell Lung CancerInoperable non–small-cell lung cancer has become the domain of combined-modality treatment based on several recent, large, phase III studies. Results of Radiation Therapy Oncology Group (RTOG) phase II studies have
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Rationale and Dose-Finding Studies of the Combination of Irinotecan and a Taxane on a Weekly ScheduleCisplatin (Platinol)-based chemotherapy has been the standard systemic therapy for both non-small-cell and small-cell lung cancer for the past 2 decades, though the efficacy and benefit remain modest. Recently, several novel
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Blood and Marrow Transplantation in Relapsed or Refractory Non-Hodgkin’s LymphomaIt was not until 1995 that a phase III randomized trial demonstrated that autologous stem cell transplants (ASCT) improve the progression-free and overall survival of patients with relapsed refractory diffuse aggressive non-Hodgkin’s lymphoma. Investigators are now focusing on improving the clinical benefit of transplants. The relative contributions made by more intensive preparative regimens, purging, concomitant immunotherapy, and the timing of transplants are under study. Also, as transplant trials shift from relapsed disease to initial therapy, anticipated benefits must be balanced against both short-term and long-term toxicities.[ONCOLOGY 12(Suppl 8):56-62, 1998]
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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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Irinotecan in Combination With Radiation Therapy for Small-Cell and Non-Small-Cell Lung CancerLung cancer is the leading cause of cancer-related death in the United States. There was rapid progress in the treatment of lung cancer during past decades, but local control and survival rates are still poor.
