Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology.
Details
Serval ID
serval:BIB_2A7B8B51C1A0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology.
Journal
Annals of Oncology
Working group(s)
Belgian Group of Digestive Oncology
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
Published
Issued date
2013
Volume
24
Number
11
Pages
2824-2829
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
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/m(2) at week 1, then 250 mg/m(2)/week) and Gemcitabine (1 g/m(2) 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.
METHODS: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m(2) at week 1, then 250 mg/m(2)/week) and Gemcitabine (1 g/m(2) 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.
Keywords
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized/administration & dosage, Antibodies, Monoclonal, Humanized/adverse effects, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bile Duct Neoplasms/drug therapy, Bile Duct Neoplasms/genetics, Cholangiocarcinoma/drug therapy, Cholangiocarcinoma/genetics, Deoxycytidine/administration & dosage, Deoxycytidine/adverse effects, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Proto-Oncogene Proteins/genetics, ras Proteins/genetics
Pubmed
Web of science
Open Access
Yes
Create date
26/01/2015 11:32
Last modification date
20/08/2019 14:10
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