Seminars in oncology
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Seminars in oncology · Oct 2001
ReviewCardiotoxicity in signal transduction therapeutics: erbB2 antibodies and the heart.
Cardiotoxicity is a common and potentially devastating side effect of antineoplastic drug therapy. This empiric observation is seen as paradoxical given that the cardiomyocyte is considered to be a terminally differentiated cell. Despite the fact that these cells do not divide after birth, adult cardiomyocytes may become "innocent bystander" targets of anticancer drugs designed to interfere with cell signaling pathways in rapidly proliferating cells. ⋯ The results obtained in these experiments support a direct action of trastuzumab on human cardiomyocytes. In addition, these data provide insight regarding potential molecular mechanisms. Most importantly, these data draw attention to the inherent risk of cardiotoxicity associated with a newly emerging class of antineoplastic drugs that interfere with signal transduction pathways.
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Seminars in oncology · Oct 2001
ReviewImatinib mesylate: clinical results in Philadelphia chromosome-positive leukemias.
Targeted cancer therapy has long been sought by the oncology community as a potentially better approach than currently available therapies. One targeted therapy that has shown great success is the tyrosine kinase inhibitor imatinib mesylate (formerly STI571, [Gleevec]; Novartis Pharmaceuticals Corp, East Hanover, NJ) which was recently approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Basic scientific investigation into the molecular causes and pathogenesis of CML and encouraging preclinical investigations on the mechanism of action of imatinib mesylate led to the initiation of phase I clinical trials. ⋯ Furthermore, 21% of patients in accelerated-phase CML and 13.5% of patients in blastic-phase CML (patient populations with typically poor prognosis before the advent of imatinib mesylate) achieved major cytogenetic responses. Results from ongoing studies will determine the durability of these responses and will evaluate ways to optimize treatment in advanced-stage patients using imatinib mesylate in combination with other therapies. Additional trials are planned to investigate the efficacy of imatinib mesylate to treat a variety of solid tumors whose pathogenesis is driven by the other tyrosine kinase targets, c-Kit and platelet-derived growth factor receptor.
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Although the initial indications of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) therapy are for refractory central nervous system malignancies (anaplastic astrocytoma in the United States and Europe, glioblastoma multiforme in Europe), a number of clinical trials are planned or ongoing to evaluate the efficacy and safety of temozolomide in newly diagnosed glioma, oligodendroglioma, pediatric glioma, brain metastases, metastatic melanoma, and other systemic tumors. Also under investigation are modifications to the temozolomide dosing schedule, other routes of administration, and treatment regimens that include temozolomide in combination with other chemotherapeutic and biologic agents. Temozolomide has the potential to be a useful agent in the treatment of a variety of cancers.
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Seminars in oncology · Aug 2001
ReviewEuropean perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has shown high clinical antitumor activity in several tumor types, including ovarian, breast, and lung carcinoma. Preclinical studies have shown that paclitaxel has an additive effect when combined with platinum compounds. Early clinical trials confirmed these data and established the dose range for both drugs. ⋯ In this trial, paclitaxel/cisplatin is delivered before etoposide/cisplatin and concurrent radiotherapy followed by surgery in locally advanced non-small cell lung cancer. Preclinical studies underline the radiosensitizing effect of paclitaxel, and many clinical studies are being conducted with radiotherapy in association with paclitaxel alone or in combination with platinum compounds. The use of paclitaxel in regimens without platinum and in triplet combinations is also being studied, and the optimal manner in which to administer this active agent clearly is of interest.
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Seminars in oncology · Aug 2001
ReviewNew cytotoxic agents and schedules for advanced breast cancer.
Cytotoxic chemotherapy is important for treatment of women with hormone-insensitive or hormone-refractory advanced breast cancer. A variety of agents are effective, alone or in combination. ⋯ Finally, the combination of chemotherapy with novel biological agents may improve outcomes for women with certain types of breast cancer. The growing availability of such biological therapies given in combination with chemotherapy may mean better survival in the future for women with advanced breast cancer.