Seminars in oncology
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Seminars in oncology · Aug 1998
ReviewEpidemiology of anthracycline cardiotoxicity in children and adults.
Anthracyclines, potent cytotoxic agents used to treat a broad spectrum of malignancies, are limited in their use by an attendant risk of cardiotoxicity. Malignancies affect all age ranges, and anthracyclines are used in all age ranges, thereby exposing a broad population of patients to the development of heart disease. For some treated patients, anthracyclines affect cardiac muscle, resulting in cardiomyopathy. ⋯ Patients with an early presentation of depressed left ventricular contractility are likely to show progression of cardiac disease with time. In addition, female gender appears to affect early and late cardiotoxicity in both adults and children, although this risk factor has been described predominantly in the survivors of childhood cancer. Thus, although anthracycline chemotherapy has improved overall survivorship of patients with cancer, there is a significant risk of cardiotoxicity associated with this class of drugs.
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Seminars in oncology · Jun 1998
ReviewDocetaxel in the management of advanced non-small cell lung cancer.
Following encouraging phase I trials in non-small cell lung cancer, the semisynthetic taxoid docetaxel has been extensively studied in the phase 11 setting, most commonly using a dose of 100 mg/m2 every 3 weeks. Major objective response rates range from 21% to 38% in previously untreated patients. ⋯ However, the median survival durations achieved do not clearly exceed those with docetaxel monotherapy. Based on preclinical evidence of synergy, docetaxel also has been combined with vinorelbine and, using prophylactic granulocyte colony-stimulating factor, it has been possible to escalate the doses of both drugs to single-agent phase II dose intensity.
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Lung cancer continues to be the leading cause of cancer-related death in both men and women. According to the American Cancer Society, 160,400 people are predicted to die from this disease in 1997. Approximately 20% to 25% of lung cancer cases are classified as small cell lung cancer (SCLC). ⋯ In particular, it is hoped that the availability of new non-cross-resistant chemotherapeutic agents such as topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a topoisomerase I inhibitor, will expand the treatment options. Because results from preclinical studies and phase I trials suggested that topotecan has activity in SCLC, the efficacy of this agent is currently being assessed in phase II and III clinical trials. Results from these trials, summarized here, suggest that topotecan may be a valuable alternative in the treatment of SCLC.
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Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a derivative of the topoisomerase I inhibitor camptothecin, was approved by the Food and Drug Administration in May 1996 for the salvage treatment of ovarian cancer. It has shown promising clinical activity in a variety of solid tumors, including cervical cancer. Phase II and III trials in patients with cisplatin-resistant ovarian cancer have been conducted using a regimen of a single 30-minute intravenous topotecan infusion (1.5 mg/m2/d) for 5 days, repeated every 21 days. ⋯ Myelosuppression is the major dose-limiting toxicity associated with topotecan. In general, the severity of myelosuppression shows a positive correlation to the magnitude of exposure to topotecan. Support with granulocyte colony-stimulating factor may partially ameliorate myelosuppressive effects.
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Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a camptothecin analog, is a novel and specific inhibitor of the nuclear enzyme topoisomerase I. In preclinical studies, topotecan demonstrated significant in vitro activity in a variety of solid tumor explants derived from colorectal, breast, ovarian, renal cell, non-small cell lung cancer, and gastrointestinal sources. Notable activity was also demonstrated in vivo in a wide range of animal tumor models. ⋯ Myelosuppression was the major dose-limiting toxicity across all schedules, and nonhematologic toxicities were generally mild. Data from phase I studies have provided valuable information about antitumor responses, maximum tolerated doses, and dose-limiting toxicities associated with different dosing schedules. Based on this information, there was substantial enthusiasm for further evaluating topotecan in a wide range of cancer patients in phase II studies.