A phase Ib trial of docetaxel, carboplatin and erlotinib in ovarian, fallopian tube and primary peritoneal cancers.

Author(s): Vasey PA, Gore M, Wilson R, Rustin G, Gabra H, Guastalla JP, Lauraine EP, Paul J, Carty K, Kaye S, Scottish Gynaecological Cancer Trials Group

Affiliation(s): CR-UK Clinical Trials Unit, Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow, Scotland G11 6NT, UK. pvasey@hoca.com.au

Publication date & source: 2008-06-03, Br J Cancer., 98(11):1774-80. Epub 2008 May 27.

Publication type: Clinical Trial, Phase I; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

The safety and maximum tolerated dose (MTD) of erlotinib with docetaxel/carboplatin were assessed in patients with ovarian cancer. Chemonaive patients received intravenous docetaxel (75 mg m(-2)) and carboplatin (area under the curve 5) on day 1 of a 3-week cycle, and oral erlotinib at 50 (cohort 1), 100 (cohort 2a) or 75 mg day(-1) (cohort 2b) for up to six cycles. Dose-limiting toxicities were determined in cycle 1. Forty-five patients (median age 59 years) received treatment. Dose-limiting toxicities occurred in 1/5/5 patients (cohorts 1/2a/2b). The MTD of erlotinib in this regimen was determined to be 75 mg day(-1) (cohort 2b; the erlotinib dose was escalated to 100 mg day(-1) in 11 out of 19 patients from cycle 2 onwards). Neutropaenia was the predominant grade 3/4 haematological toxicity (85/100/95% respectively). Common non-haematological toxicities were diarrhoea, fatigue, nausea and rash. There were five complete and seven partial responses in 23 evaluable patients (52% response rate). Docetaxel/carboplatin had no measurable effect on erlotinib pharmacokinetics. In subsequent single-agent maintenance, erlotinib was given at 100-150 mg day(-1), with manageable toxicity, until tumour progression. Further investigation of erlotinib in epithelial ovarian carcinoma may be warranted, particularly as maintenance therapy.