Paclitaxel administered by a 1-hour infusion: A phase I-II trial comparing two schedules.

PURPOSE

Paclitaxel is currently administered by prolonged intravenous infusion primarily because of severe hypersensitivity reactions that occurred with rapid infusions during early clinical trails. This phase I-II study evaluates the feasibility of 1-hour paclitaxel administration and compares the toxicity and efficacy of two different 1-hour infusion schedules.

PATIENTS AND METHODS

One hundred sixty-four patients with advanced, refractory cancer were randomized to receive one of two paclitaxel schedules: a 1-hour infusion or a 3-day, divided dose schedule, each daily dose administered by 1-hour infusion. The first 60 patients received a total paclitaxel dose of 135 mg/m2, and the remaining 104 patients received 200 mg/m2. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Cytokines were not routinely used.

RESULTS

No serious hypersensitivity reactions occurred in 620 courses of paclitaxel. Both doses were well tolerated; grade 3 or 4 leukopenia was produced in 22% of courses at 135 mg/m2 and 23% of courses at 200 mg/m2. Both schedules were well tolerated, but grade 3 and 4 leukopenia was more common with the 3-day schedule when paclitaxel 200 mg/m2 was administered. Myalagias were more common with the 1-day schedule. Major responses occurred in 35 of 153 evaluable patients (23%). Response rates in ovarian, breast, and non-small cell lung cancer were 45%, 33%, and 25%, respectively. At the 200 mg/m2 dose, 11 of 36 patients (31%) with non-small cell lung cancer responded, including 6 of 16 who had received previous chemotherapy. No major difference in response rates was observed when the 1-day and 3-day schedules were compared.

CONCLUSIONS

Paclitaxel can be safely administered by 1-hour infusion in an outpatient setting. A dose of 200 mg/m2 is well tolerated without the use of cytokines. Both schedules are well tolerated; however, the 3-day schedule produces more leukopenia when a 200 mg/m2 dose is administered. Antitumor activity was seen with both doses and schedules. Administration of paclitaxel over 1-hour is less toxic, easier, and less expensive than are prolonged infusions, and deserves continued investigation.