title: A phase Ib trial of docetaxel, carboplatin and erlotinib in ovarian, fallopian tube and primary peritoneal cancers.
abstract: 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.
authors.affiliation: CR-UK Clinical Trials Unit, Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow, Scotland G11 6NT, UK. pvasey@hoca.com.au
authors.forename: P A
authors.initials: PA
authors.lastname: Vasey
authors.forename: M
authors.initials: M
authors.lastname: Gore
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.forename: G
authors.initials: G
authors.lastname: Rustin
authors.forename: H
authors.initials: H
authors.lastname: Gabra
authors.forename: J-P
authors.initials: JP
authors.lastname: Guastalla
authors.forename: E P
authors.initials: EP
authors.lastname: Lauraine
authors.forename: J
authors.initials: J
authors.lastname: Paul
authors.forename: K
authors.initials: K
authors.lastname: Carty
authors.forename: S
authors.initials: S
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride