Clinical phase I study with one-hour paclitaxel infusion.
BACKGROUND
Paclitaxel (PAC) is one of the major anti-cancer drugs, effective in different tumors. Studies with 24-hour infusion with 135 mg/m2 and a three-hour infusion with 175 mg/m2 showed a significant schedule-dependent toxicity. We evaluated a one-hour infusion schedule within a phase I study to determine the dose limiting toxicity (DLT), the maximum tolerated dose (MTD), and the anti-cancer efficacy.


METHODS
Patients with advanced malignant tumors were treated within cohorts by one-hour infusional paclitaxel starting with 150 mg/m2 and stepwise escalation with 25 mg/m2 increments. Therapy was repeated in three-week intervals. Cycles were repeated until progression. Toxicity was closely monitored, anti-cancer efficacy was only evaluated in those patients who received at minimum two treatment cycles.


RESULTS
Thirty-four patients entered the study (11 NSCLC, five SCLC, seven ovarian cancer, one cervix cancer, nine MBC, one HN cancer). The MTD was PAC 250 mg/m2. The DLT was central and peripheral neuropathy (WHO grade 3). Other significant toxicities were fatigue, myalgia/arthralgia and paraesthesia. No significant myelotoxicity was observed. Totally twentyone patients were evaluable for response. A partial response was observed in five (24%) patients (two NSCLC, two ovarian cancer, one head and neck cancer). Three (14%) patients had stable disease and in 13 (62%) patients progressive disease was observed.


CONCLUSIONS
Paclitaxel 225 mg/m2 on day 1 administered as one-hour infusion and repeated every three weeks can be given safely, featured no relevant myelotoxicity, and is the recommended dose for phase II studies.
Mross
K
K
Department of Medical Oncology and Clinical Pharmacology, Tumor Biology Center at the Albert-Ludwigs University Freiburg, Germany. mrkl@tumorbio.uni-freiburg.de
Hauns
B
B
Häring
B
B
Bauknecht
T
T
Meerpohl
H G
HG
Unger
C
C
Maier-Lenz
H
H
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel