Erlotinib in combination with capecitabine and docetaxel in patients with metastatic breast cancer: A dose-escalation study

• Published in: European journal of cancer (1990) Vol. 44; no. 3; pp. 419 - 426
• Main Authors: Twelves, Chris, Trigo, José M, Jones, Rob, De Rosa, Flavio, Rakhit, Ashok, Fettner, Scott, Wright, Tonya, Baselga, José
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.02.2008; Elsevier
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Biological and medical sciences; Breast Neoplasms - drug therapy; Capecitabine; Cohort Studies; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacokinetics; Docetaxel; Dose-escalation; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Erlotinib; Erlotinib Hydrochloride; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - analogs & derivatives; Fluorouracil - pharmacokinetics; Hematology, Oncology and Palliative Medicine; Humans; Maximum Tolerated Dose; Maximum-tolerated dose (MTD); Medical sciences; Metastatic breast cancer (MBC); Middle Aged; Neoplasm Metastasis; Pharmacokinetics; Pharmacology. Drug treatments; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - pharmacokinetics; Taxoids - administration & dosage; Taxoids - adverse effects; Taxoids - pharmacokinetics; Treatment Outcome; Triple-drug combination; Tumors; Erlotinib; Metastatic breast cancer (MBC); Capecitabine; Docetaxel; Dose-escalation; Pharmacokinetics; Triple-drug combination; Maximum-tolerated dose (MTD); Antineoplastic agent; Quinazoline derivatives; Metastasis; Increasing dose; Cancerology; Taxane derivatives; Advanced stage; Antimitotic; Protein-tyrosine kinase; Pyrimidine nucleoside; Human; Drug combination; Enzyme; Tyrosine kinase inhibitor; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Breast cancer; Pharmacology; Malignant tumor; Mammary gland diseases; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2007.12.011

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 100 mg/day continuously, capecitabine 825 mg/m2 bid on days 1 to 14 and docetaxel 75 mg/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.