A phase I study of a weekly schedule of paclitaxel and carboplatin in patients with advanced carcinoma

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Abstract
BACKGROUND: We conducted a Phase I study of weekly paclitaxel (P) and carboplatin (C) in patients with advanced malignancies to determine the maximum tolerated dose (MTD) of this combination.METHODS: Dose levels were escalated independently for patients with and without previous chemotherapy exposure and advanced malignancies. Both agents were administered weekly for 6 weeks followed by a 2‐week break per cycle. P, escalated to tolerance starting at 135 mg/m2 per week, and C, fixed dose at area under the curve (AUC) = 2 mg/mL/min, were administered to groups of three or six patients. Doses were modified for granulocyte counts less than 1800/μL or for neurotoxicity greater than Grade 1. MTD was defined as the highest dose level at which less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended dose during the first cycle. Dose levels were escalated until these conditions were exceeded.RESULTS: Twenty‐seven patients (12 patients with previous chemotherapy exposure and 15 chemotherapy‐naive patients) were examined for toxicity. Dose escalation was halted due to neutropenia and/or Grade 2/3 neuropathy in both arms. The MTD was P = 135/C = 2 for patients with previous chemotherapy exposure and P = 150/C = 2 for chemotherapy‐naive patients.CONCLUSIONS: The combination of P and C administered on a weekly schedule permits a two to threefoldenhancement of P dose intensity with full doses of C. Phase II trials of this regimen in patients with various malignancies are being evaluated to determine efficacy and tolerance. Cancer 2002;95:2000–5. © 2002 American Cancer Society.DOI 10.1002/cncr.10902