Phase I clinical trial of weekly combined paclitaxel plus docetaxel in patients with solid tumors

A Phase I and feasibility study of combined docetaxel (D) plus paclitaxel (P) was undertaken to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for each analogue delivered concomitantly on a weekly schedule.

Patients were accrued in 3-6 patient cohorts to P administered over a course of 45-60 minutes followed by D infused over a course of 30 minutes for 4 consecutive weeks with the cycles repeated at 6 weeks. The MTD was defined as the dose of each agent administered with at least Grade 3 (according to National Cancer Institute standard criteria) hematologic toxicity in 50% of the patients but without Grade 4 toxicity.

Twenty patients received D plus P weekly for 4 weeks at 4 dose levels. At the highest P dose (80 mg/m2; total dose per cycle, 320 mg/m2) 2 of 6 patients received treatment for 4 consecutive weeks but 5 of 6 patients developed hematologic and/or nonhematologic (skin) DLTs. The recommended treatment doses for this combined taxane regimen is D, 35 mg/m2/week, plus P, 65 mg/m2/week, for 4 weeks. An unusual cutaneous syndrome was observed in four patients that was manifested as erythema and blistering on the dorsum of the hands.

The lack of complete cross-resistance for D and P in experimental systems and the clinical observation that tumor resistance to one taxane does not necessarily convey resistance to the alternative taxane was the basis for exploring the use of both analogues administered simultaneously. This Phase I trial establishes the optimal weekly dose for each taxane when administered in combination.