[Phase I study of paclitaxel].
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.
Horikoshi
N
N
Dept. of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research.
Inoue
K
K
Aiba
K
K
Mukaiyama
T
T
Ogihara
A
A
Sumida
T
T
Akatsuka
Y
Y
Besho
A
A
Inamoto
Y
Y
Uchida
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D017239:Paclitaxel