Seminars in oncology
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Seminars in oncology · Aug 1997
ReviewDocetaxel in combination chemotherapy for metastatic breast cancer.
Due to its novel mechanism of action, docetaxel has significant in vitro activity against a variety of solid tumors, including breast cancer. In phase II clinical trials, docetaxel 100 mg/m2 every 3 weeks has shown substantial single-agent activity in patients with both previously untreated and heavily pretreated metastatic breast cancer. As single-agent chemotherapy is rarely curative in this setting, docetaxel has been combined with other anticancer agents with proven efficacy against breast cancer (doxorubicin, vinorelbine, fluorouracil, cyclophosphamide, cisplatin, and doxorubicin plus cyclophosphamide) in an attempt to increase efficacy and prolong patient survival. ⋯ Combination studies with fluorouracil, cisplatin, and cyclophosphamide, and a study of sequential administration with doxorubicin + cyclophosphamide, are ongoing. Interim results indicate that these docetaxel-based combinations have acceptable safety profiles and encouraging levels of antitumor activity. The full results of these studies will help to elucidate the potential contribution of docetaxel-based combination chemotherapy to the management of metastatic breast cancer.
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Seminars in oncology · Aug 1997
ReviewFuture perspectives of docetaxel (Taxotere) in front-line therapy.
The recognition that early breast cancer is a systemic disease has led to the development of multimodal treatments incorporating adjuvant hormonal and chemotherapies. Adjuvant strategies have improved the outcome of treatment for early breast cancer, but 50% of women still relapse and develop overt metastatic disease, which is largely incurable. In the search for more effective chemotherapies, the taxoid, docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France), has demonstrated high single-agent activity against metastatic breast cancer, including visceral metastases, and is now in phase III trials of combination adjuvant and front-line therapies. ⋯ The high single-agent activity of docetaxel makes it an excellent candidate for treatments such as induction regimens before high-dose chemotherapy and adjuvant therapies. Short-term treatment regimens such as these should also avoid the cumulative toxicities of docetaxel. It is important that new drugs, such as docetaxel, which have shown promising activity against metastatic disease and could have a significant impact on the natural history of early breast cancer, are investigated as front-line treatments.
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Seminars in oncology · Aug 1997
Review Case ReportsSimultaneous paclitaxel and radiotherapy: initial clinical experience in lung cancer and other malignancies.
This report summarizes results from a series of pilot trials using combined-modality chemoradiotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a radiosensitizing agent in patients with cancers of the lung, cervix, and bladder. In a phase I study of paclitaxel/radiotherapy in patients with locally advanced non-small cell lung cancer, five paclitaxel dose levels were evaluated in conjunction with simultaneous radiation (total dose, 59.4 Gy). A minimum of five patients were treated at each dose level; paclitaxel doses ranged from 45 mg/m2 over 3 weeks (level 1) to 65 mg/m2 for 7 weeks. ⋯ The investigators next conducted a trial of paclitaxel 50 mg/m2 given weekly over 3 hours with the previous carboplatin/radiotherapy regimen in four women and documented two partial responses, one near-complete response, and one minor response, with moderate, manageable toxicity. In a final case report on a patient with recurrent bladder cancer, simultaneous radiotherapy and weekly paclitaxel 50 mg/m2 intravenously over 3 hours yielded a partial remission, prompting the investigators to plan a phase I study to confirm the regimen's efficacy and safety. Additional planned studies include a phase I trial of simultaneous chemoradiotherapy in patients with cancer of the head and neck.
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Seminars in oncology · Aug 1997
ReviewHigh-dose therapy with carboplatin and paclitaxel in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer deaths in the United States. The combination of more active agents like vinorelbine and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with cisplatin has led to improved survival for patients with advanced metastatic disease. The ability to escalate the dose of cisplatin-based regimens is limited by nonhematologic toxicities and is especially difficult in the population of patients with advanced NSCLC. ⋯ Depending on response to induction therapy, patients then receive surgical resection, thoracic radiation therapy, or both. This phase II trial will examine clinical and pathologic responses and the toxicity of this high-dose regimen in patients with locally advanced NSCLC. Ultimately, phase III trials will be needed to establish the role of this approach in NSCLC.
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Seminars in oncology · Aug 1997
ReviewDefining the role of paclitaxel in lung cancer: summary of recent studies and implications for future directions.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was first reported to have activity in advanced non-small cell lung cancer (NSCLC) in 1993 and in advanced small cell lung cancer (SCLC) in 1995. Since these original reports, single-agent activity has been confirmed in both NSCLC and SCLC. In NSCLC, the 20% to 25% response rate and median survival times (approximately 40 weeks) are superior to previously reported single-agent therapy. ⋯ Similarly, paclitaxel and carboplatin combinations produce high response rates when given before surgery for operable patients, and the results of randomized trials are needed to confirm the value of this approach. Paclitaxel-based combinations in advanced SCLC can be administered safely and provide high response rates and relatively long survival times. Randomized trials comparing these combinations to older etoposide/cisplatin combinations are in progress.