title: Erlotinib in combination with capecitabine and docetaxel in patients with metastatic breast cancer: a dose-escalation study.
abstract: Capecitabine added to docetaxel extends survival in metastatic breast cancer (MBC) and shows additive efficacy with erlotinib in pre-clinical studies. This study aimed to determine the maximum-tolerated dose (MTD) of capecitabine/docetaxel with erlotinib and assess tolerability, anti-tumour activity and potential pharmacokinetic interactions. Three treatment cohorts were assessed, using different dosing regimens. A total of 24 women with MBC were enrolled sequentially. The regimen comprising erlotinib 100mg/day continuously, capecitabine 825mg/m2 bid on days 1 to 14 and docetaxel 75mg/m2 intravenously every 3 weeks on day 1 was well tolerated and was established as the MTD. Overall response rate was 67%, comprising two complete and 12 partial responders in 21 assessable patients. The most common treatment-related adverse events were gastrointestinal disorders and skin toxicities. Pharmacokinetic studies showed that exposure to the three drugs was not reduced when given in combination. These encouraging preliminary results warrant further trials of the combination in MBC.
authors.affiliation: University of Leeds and St. James Hospital, Leeds, United Kingdom. c.j.twelves@leeds.ac.uk
authors.forename: Chris
authors.initials: C
authors.lastname: Twelves
authors.forename: José M
authors.initials: JM
authors.lastname: Trigo
authors.forename: Rob
authors.initials: R
authors.lastname: Jones
authors.forename: Flavio
authors.initials: F
authors.lastname: De Rosa
authors.forename: Ashok
authors.initials: A
authors.lastname: Rakhit
authors.forename: Scott
authors.initials: S
authors.lastname: Fettner
authors.forename: Tonya
authors.initials: T
authors.lastname: Wright
authors.forename: José
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil