Phase i study of paclitaxel
Horikoshi, N.; Inoue, K.; Aiba, K.; Mukaiyama, T.; Ogihara, A.; Sumida, T.; Akatsuka, Y.; Besho, A.; Inamoto, Y.; Uchida, T.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 21(14): 2407-2414
1994
ISSN/ISBN: 0385-0684 PMID: 7944484 Document Number: 431427
Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.