A phase I study of a weekly schedule of paclitaxel and carboplatin in patients with advanced carcinoma.
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.
Akerley
Wallace
W
Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, USA. Wallace.Akerley@HCI.utah.edu
Rathore
Ritesh
R
Ready
Neil
N
Leone
Louis
L
Sikov
William
W
Safran
Howard
H
Kennedy
Teresa
T
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects
D016190:Carboplatin; D017239:Paclitaxel