Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology

Background: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. Methods: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m2 at week 1, then 250 mg/m2/week) and Gemcitabine (1 g/m2 on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. Results: Forty-four patients (4... Mehr ...

Verfasser: Borbath, Ivan
Ceratti, Antonino
Verslype, Chris
Demols, Anne
Delaunoit, Thierry
Laurent, Stéphanie
Deleporte, Amélie
Vergauwe, Philippe L
Van Maanen, Aline
Sempoux, Christine
Van Cutsem, Eric
Van Laethem , Jean Luc
Belgian Group of Digestive Oncology
Dokumenttyp: Artikel
Erscheinungsdatum: 2013
Verlag/Hrsg.: Oxford University Press
Schlagwörter: Adult / Female / Humans / Kaplan-Meier Estimate / Male / Middle Aged / Proto-Oncogene Proteins / ras Proteins / Aged / 80 and over / Antibodies / Monoclonal / Humanized / Antineoplastic Combined Chemotherapy Protocols / Bile Duct Neoplasms / Cholangiocarcinoma / Deoxycytidine / Disease-Free Survival
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-28489820
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://hdl.handle.net/2078.1/156079

Background: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. Methods: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m2 at week 1, then 250 mg/m2/week) and Gemcitabine (1 g/m2 on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. Results: Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect =grade 2 was associated with increased PFS (P = 0.05).Conclusion(s): Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy.