Seminars in oncology
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Seminars in oncology · Aug 1997
Clinical TrialPreliminary results of a phase II study of paclitaxel and cisplatin in patients with non-small cell lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin are cytotoxic drugs active against non-small cell lung cancer (NSCLC) that possess additive cytotoxicity in animal tumors. Paclitaxel and cisplatin are active in patients with advanced NSCLC when given on a 3-weekly schedule. In an attempt to increase activity, we designed a phase II study with a biweekly schedule. ⋯ Median response duration was 31 weeks (range, 9 to 85 weeks). The biweekly schedule of paclitaxel plus cisplatin has noteworthy activity in patients with NSCLC. A relatively large fraction of patients required either dose reduction and/or treatment delay, but World Health Organization grade 3 or 4 toxicity was rare, apart from the neutropenia that caused only a few septicemic episodes.
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Seminars in oncology · Aug 1997
Randomized Controlled Trial Clinical TrialThe role of docetaxel (Taxotere) as a single agent or in combination before local treatment of non-small cell lung cancer.
Neoadjuvant therapy in the treatment of stage IIIa/b non-small cell lung cancer (NSCLC) has the potential to reduce tumor size in patients whose tumors were previously inoperable. This report describes the design and status of an ongoing randomized, phase III study of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) as neoadjuvant treatment in patients with stage IIIa/b NSCLC, as well as of two phase II studies of combination neoadjuvant therapies. A phase III, multicenter, international, randomized trial is in progress which compares docetaxel with no neoadjuvant chemotherapy in patients with histologically confirmed, previously untreated NSCLC with stage IIIa N2(T0-3) or T3 (N0-1) disease or stage IIIb disease that can be treated radically. ⋯ The primary objective of the study is to determine the response rate after chemotherapy. The results of both studies should be available by late 1997. The ultimate hope is that there is potential for neoadjuvant chemotherapy to provide a significant benefit for patients with advanced NSCLC.
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Seminars in oncology · Aug 1997
Clinical TrialPaclitaxel (3-hour infusion) followed by carboplatin (24 hours after paclitaxel): a phase II study in advanced non-small cell lung cancer.
This phase II study was performed to investigate the efficacy of a 3-hour 225 mg/m2 paclitaxel infusion (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) followed 24 hours later by a 30-minute infusion of carboplatin (dosed to an area under the concentration-time curve of 6) in patients with stage IIIA, IIIB, or IV non-small cell lung cancer. Patients received chemotherapy and were monitored for toxicity, response, quality of life, and survival. Paclitaxel and carboplatin pharmacokinetics were also determined with the first cycle of chemotherapy. ⋯ Physical and emotional well-being improved in 57%, functional well-being in 43%, and social/family well-being in 14% of patients. Pharmacokinetic data are being analyzed by limited sampling technique to predict the paclitaxel area under the concentration-time curve. This unique schedule of paclitaxel and carboplatin is well tolerated and active, and is associated with improvements in various aspects of quality of life.
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Seminars in oncology · Aug 1997
Clinical TrialDocetaxel (Taxotere) and vinorelbine in the treatment of advanced non-small cell lung cancer: preliminary results of a phase I/II trial.
We undertook a phase I/II study of the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and vinorelbine in the treatment of unresectable or metastatic non-small cell lung cancer (NSCLC). Nineteen patients with unresectable NSCLC received a combination of docetaxel 50 mg/m2 and vinorelbine 15 to 45 mg/m2 every 2 weeks. All patients received prophylactic granulocyte-colony stimulating factor 5 microg/kg/d and corticosteroids. ⋯ Further dose escalation is needed to determine the maximum tolerated dose of the combination. A partial response was observed in five patients (26%; 95% confidence interval, 15% to 57%), and nine (47%) patients showed stable disease. Based on these preliminary results, the combination of these two drugs appears to have antitumor activity against NSCLC and warrants continued study.
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Seminars in oncology · Aug 1997
Clinical TrialPaclitaxel (1-hour) and carboplatin (area under the concentration-time curve 7.5) in advanced non-small cell lung cancer: a phase II study of the Fox Chase Cancer Center and its network.
We previously reported a 62% response rate and 54% 1-year survival rate for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 24-hour infusion in combination with fixed-dose carboplatin to treat patients with advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose limiting, but was substantially reduced by the routine use of granulocyte colony-stimulating factor during the second and subsequent cycles. Activity for paclitaxel 135 mg/m2 and 200 mg/m2 by 1-hour infusion every 3 weeks in patients with NSCLC, with minimal myelosuppression and the suggestion of a dose-response relationship, has been reported. ⋯ Paclitaxel given by 1-hour infusion in combination with carboplatin at a fixed target area under the concentration-time curve of 7.5, although active in advanced NSCLC, is associated with problems that compromise its efficacy. Higher dose levels yield intolerable toxicity, evidenced by the incidence of neurotoxicity (rather than myelosuppression) that was dose and protocol limiting at paclitaxel doses exceeding 215 mg/m2. Lower doses, while more tolerable, appear to be associated with lower response rates.