Cetuximab, gemcitabine and capecitabine in patients with inoperable biliary tract cancer: a phase 2 study

Purpose Biliary tract cancer is rare and has dismal prognosis. Chemotherapy has its role in inoperable disease but the role of targeted agents like cetuximab remains to be defined. On the basis of high epidermal growth factor receptor expression of biliary tract cancers this study aims to investigate the efficacy of cetuximab, gemcitabine and capecitabine in an exploratory phase 2 trial. Patients and methods Inoperable biliary tract cancer patients were treated with the combination of gemcitabine (1000 mg/m2 on day 1 and 8), capecitabine (1300 mg/m2/d on day 1–14) and weekly cetuximab (400 mg/m2 loading and 250 mg/m2 maintenance dose) in 21-d cycles until progression or the appearance of intolerable side-effects. Results Out of 34 patients (mean age 59.7 years) accrued in this study 16 had intrahepatic, eight extrahepatic cholangiocarcinoma and 10 gall bladder cancer. The best overall response rate was 17.6% (two complete responses and four partial responses) and the clinical benefit rate was 76.5%. After a median of 15.4 months follow-up the median progression free survival was 34.3 weeks and the median overall survival was 62.8 weeks. The performance status and chemotherapy efficacy were independent and significant markers of survival. Only moderate side-effects were registered in this study. KRAS mutation was evaluable in 24 tumours, all of these were of wild type. Conclusion The efficacy of cetuximab, gemcitabine and capecitabine combination is encouraging and a well tolerated treatment of inoperable biliary tract cancers.