Seminars in oncology
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Seminars in oncology · Dec 2009
ReviewClinical trial experience with temsirolimus in patients with advanced renal cell carcinoma.
Clinical trials have validated the importance of mammalian target of rapamycin (mTOR) as a therapeutic target in patients with advanced renal cell carcinoma (RCC). The TORC1 complex controls translation of key proteins involved in cell proliferation and regulates the expression and stability of hypoxia-inducible factor (HIF)-1alpha. Temsirolimus, the first mTOR inhibitor approved for treatment of advanced RCC, has demonstrated significantly longer overall survival (hazard ratio for death, 0.73; 95% confidence interval, 0.58-0.92, P = .008) and progression-free survival (P <.001) compared with interferon alfa (IFN) for patients with poor prognostic features. ⋯ Although development of symptomatic pneumonitis is rare, monitoring is recommended. Temsirolimus is now considered an important first-line treatment option for patients with advanced RCC and multiple factors predictive of short survival. Current trials are investigating the use of temsirolimus in sequence or in combination with other targeted agents to further improve outcomes.
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Seminars in oncology · Aug 2009
Review Randomized Controlled TrialShould intra-cerebrospinal fluid prophylaxis be part of initial therapy for patients with non-Hodgkin lymphoma: what we know, and how we can find out more.
Central nervous system (CNS) involvement is a serious complication of non-Hodgkin lymphoma (NHL), with an extremely poor outcome. In most cases, relapse in the CNS manifests as leptomeningeal disease. The relatively short interval between the initial diagnosis of NHL and CNS involvement implies that seeding of the cerebrospinal fluid occurs early in the natural history of the disease and suggests a role for CNS prophylaxis during initial treatment. ⋯ Risk factors for CNS relapse in patients with aggressive NHL have been identified and may help define a subpopulation of patients for whom CNS prophylaxis is justified. Because of variation in current practice and a paucity of high-quality evidence, well-designed and controlled trials are needed to assess the benefits of prophylactic treatment in such a population. This article reviews the current role of CNS prophylaxis in patients with NHL and discusses issues in the conception, design, and execution of a clinical trial to elucidate the role of CNS prophylaxis in patients with aggressive NHL.
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Seminars in oncology · Aug 2009
Understanding the origins of gliomas and developing novel therapies: cerebrospinal fluid and subventricular zone interplay.
Glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, carries a poor prognosis, with median survival generally less than 1 year. Although initial therapy often eradicates the bulk of the tumor, disease recurrence, usually within 2 cm of the original tumor, is almost inevitable. This may be due to a failure of current therapies to eradicate viable chemotherapy- and radiotherapy-resistant neoplastic progenitor cells, which may then repopulate tumors. ⋯ Therapeutic targeting of SVZ stem cell populations via cerebrospinal fluid (CSF)-directed therapy may provide a means for limiting tumor recurrence. This approach has proved successful in the treatment of medulloblastoma, another brain tumor thought to be derived from stem cells. We discuss the rationale and design considerations for a clinical trial to evaluate the efficacy of CSF-directed therapy for preventing GBM recurrence.
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Seminars in oncology · Apr 2008
ReviewPreclinical investigations with epothilones in breast cancer models.
The epothilones constitute a novel class of microtubule inhibitors that act like the taxanes by hyperstabilizing tubulin polymerization, thus disrupting functioning of the mitotic spindle. Natural epothilones produced by myxobacteria, and second- or third-generation partially or fully synthesized analogs, have been explored as cancer chemotherapy agents to replace or follow the taxanes. ⋯ Comparable antitumor activity has been demonstrated against nude mouse xenografts of paclitaxel-sensitive and -resistant breast cancer lines. Additionally, some analogs have reduced toxicity or increased water solubility that may permit oral administration, while others with enhanced tissue penetration show promise in animal models of breast cancer brain or bone metastasis and may provide benefits in patients with poor-prognosis advanced breast cancer.
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Seminars in oncology · Dec 2007
ReviewRandomized adjuvant therapy trials in melanoma: surgical and systemic.
The utility of adjuvant surgical procedures in the management of primary melanomas has been evaluated in a large number of phase III randomized trials. These trials have shown that wide margins, elective lymph node dissection, sentinel lymph node (SLN) biopsy, and prophylactic isolated limb perfusion (ILP) do not improve survival but may improve locoregional control. Based on the claim of providing a survival benefit, these surgical procedures cannot be considered standard of care in the routine management of primary melanoma. ⋯ Interferon (IFN) has an effect on relapse-free survival but not on overall survival. Thus its impact is judged by many to be too small to be considered standard of care. The population of patients that can benefit from IFN needs to be better defined by identifying new biomarkers by genomic and proteomic studies, which are ongoing.