Seminars in oncology
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Seminars in oncology · Dec 1997
ReviewStereotactic radiosurgery and radiotherapy: new developments and new directions.
Stereotactic irradiation is a precise method for the delivery of focused radiation beams to small intracranial targets. Treatment can be administered in single or multiple fractions (radiosurgery or stereotactic radiotherapy, respectively). The technology has evolved rapidly because of advances in both hardware and software design. Clinical indications are unfolding through the prospective trial mechanism.
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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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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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Seminars in oncology · Dec 1997
ReviewTreatment of patients with upper gastrointestinal carcinomas.
Carcinomas of the stomach and esophagus are a major health problem worldwide. Cancer remains incurable when it is metastatic or unresectable, and new active agents are needed to improve the outcome for these patients. Three phase II studies of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are described here. ⋯ Toxicity with this combination has been moderate, and there have been no treatment-related deaths. With the reduced starting dose of 5-fluorouracil, the tolerance of this combination has improved substantially both in the inpatient and outpatient settings, resulting in a low frequency of grade 3 or 4 nonhematologic toxicity. Response has been higher in patients with squamous cell carcinoma.
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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.