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 (41% l... Mehr ...

Verfasser: Borbath, I.
Ceratti, A.
Verslype, C.
Demols, A.
Delaunoit, T.
Laurent, S.
Deleporte, A.
Vergauwe, P.
Van Maanen, A.
Sempoux, C.
Van Cutsem, E.
Van Laethem, J. L.
on behalf of the Belgian Group of Digestive Oncology
Dokumenttyp: TEXT
Erscheinungsdatum: 2013
Verlag/Hrsg.: Oxford University Press
Schlagwörter: Original article
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-28886945
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://annonc.oxfordjournals.org/cgi/content/short/mdt337v1

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. ClinicalTrials.gov Identifier: NCT00747097.