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A phase I study of a weekly schedule of paclitaxel and carboplatin in patients with advanced carcinoma
Author(s) -
Akerley Wallace,
Rathore Ritesh,
Ready Neil,
Leone Louis,
Sikov William,
Safran Howard,
Kennedy Teresa
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10902
Subject(s) - medicine , carboplatin , paclitaxel , schedule , oncology , carcinoma , chemotherapy , cisplatin , computer science , operating system
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/m 2 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