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
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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Seminars in oncology · Dec 1997
Clinical TrialConcurrent paclitaxel, carboplatin, and radiotherapy in advanced head and neck cancers: a phase II study--preliminary results.
Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. ⋯ Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.
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Surgery and radiation for advanced head and neck cancer are debilitating and associated with poor survival. If outpatient preoperative chemotherapy could be used such that smaller surgical resections are needed, organs might be preserved and patients' quality of life enhanced. Accordingly, we are conducting a phase I trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin in previously untreated patients with advanced head and neck cancer. ⋯ The dose-limiting toxicity that occurred at paclitaxel 265 mg/m2 comprised grade 3/4 neutropenia and thrombocytopenia with associated cumulative grade 2 neuropathy. The maximum tolerated dose of paclitaxel with the combination will be between 230 and 265 mg/m2. This combination has activity in head and neck cancer.
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Seminars in oncology · Dec 1997
Clinical TrialCombined-modality therapy for esophageal cancer: phase I trial of escalating doses of paclitaxel in combination with cisplatin, 5-fluorouracil, and high-dose radiation before esophagectomy.
Several recent reports support administering preoperative chemotherapy and radiotherapy to improve the outcome of patients with resectable esophageal malignancies. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), 5-fluorouracil (5-FU), and cisplatin are known radiosensitizers, and paclitaxel has demonstrated single-agent activity in patients with metastatic esophageal cancer. This study sought to define the maximum tolerated dose of paclitaxel given with 5-FU, cisplatin, and 60 Gy radiotherapy before esophagectomy to patients with potentially resectable lesions. ⋯ Three relapses occurred at 26, 33, and 43 weeks. We conclude that this is an intense combined-modality preoperative regimen for patients with esophageal cancer. Determining the efficacy of this regimen will require further follow-up and the performance of phase II trials.