Phase Ii dose escalation: a novel approach to balancing efficacy and toxicity of anticancer agents. Japanese Docetaxel Ovarian Cancer Study Group
Fujiwara, K.; Kohno, I.; Tanaka, K.; Ogita, S.; Sasaki, Y.; Hirabayashi, K.; Yakushiji, M.; Tsunematsu, R.; Terashima, Y.; Taguchi, T.; Ohashi, Y.; Noda, K.
Anticancer Research 19(1b): 639-644
1999
ISSN/ISBN: 0250-7005 PMID: 10216469 Document Number: 502572
Small patient numbers in phase I trials may result in a safe but ineffective dose being recommended for phase II trials. A phase II dose escalation study may identify a dose that is both safe and effective. The Japanese phase I recommended dose of 60 mg/m2 of docetaxel (Taxotere) had been ineffective in phase II trials in ovarian carcinoma. Patients previously treated with one platinum-based regimen for ovarian cancer received docetaxel (Taxotere) every 3 weeks. The first dose tested was 70 mg/m2. If none of the first 5 evaluable patients responded, the dose was increased. If at least one patient responded, 10 more patients were enrolled. Also, if fewer than 3 of these first 15 evaluable patients responded, the dose was increased. If at least 3 patients responded, another 15 patients were scheduled to be enrolled to confirm efficacy. Unacceptable toxicity in 4 of 5, or 10 of 15 patients would stop escalation. Dose escalation from 70 mg/m2 was not required because responses were noted with acceptable toxicity levels. Overall response in 25 evaluable patients treated at 70 mg/m2 was 24.0% (95% CI = 9.4-45.1%). Docetaxel 70 mg/m2 without premedication was identified as a safe and effective dose. Further testing of the phase II dose escalation design is worthwhile.