Seminars in oncology
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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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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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Seminars in oncology · Dec 1997
Clinical TrialSeven-week continuous-infusion paclitaxel with concurrent radiotherapy for locally advanced head and neck squamous cell cancer: a phase I study.
The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7-week total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with standard curative radiotherapy (RT) for previously untreated, locally advanced head and neck squamous cell cancers. Eligible patients have squamous cell cancers of the head and neck with expected 5-year survival rates of < or =25%; a good performance status; adequate hematologic, hepatic, and renal functions; and no distant metastases. All patients receive 70 Gy megavoltage RT in 7 weeks (2 Gy/d x 5 d/wk). ⋯ This therapy is feasible and has been well tolerated through current dose levels with no dose-limiting toxicity. There is a suggestion of biologic activity evidenced by the anemia and the possibility of alteration in cell-cycle distributions. Dose escalation is ongoing.
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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 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.