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

✍ Scribed by Wallace Akerley; Ritesh Rathore; Neil Ready; Louis Leone; William Sikov; Howard Safran; Teresa Kennedy

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 64 KB
• Volume: 95
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.10902

✦ Synopsis

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/microl 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 threefold enhancement 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.