The evidence supporting this protocol is provided by a randomised phase III study involving 410 patients comparing cisplatin plus gemcitabine with gemcitabine alone in patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer.r
Between February 2002 and October 2008, a total of 204 patients received cisplatin 25 mg/m2 plus gemcitabine 1000 mg/m2 days 1 and 8 every 3 weeks, and 206 received gemcitabine 1000 mg/m2 days 1, 8 and 15 every 4 weeks alone.
The primary outcome was overall survival, and the secondary outcomes were progression-free survival, tumour response, and adverse events.r
A meta analysis of the above trialr and a similar phase 2 trial conducted in Japanr confirmed that cisplatin gemcitabine combination chemotherapy are the standard of care for first line treatment of advanced cholangiocarcinoma regardless of ethnicity. It showed significant improvement in median PFS 8.8 versus 6.7 months [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.53–0.76, P < 0.001] and median OS 11.6 versus 8.0 months(HR = 0.65, 95% CI 0.54–0.78, P < 0.001) over gemcitabine monotherapy.r
Efficacy
After a median follow-up of 8.2 months, the median overall survival was 11.7 months in the cisplatin-gemcitabine group and 8.1 months in the gemcitabine group (HR, 0.64; 95% CI, 0.52 to 0.80; p<0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (p<0.001). The rate of tumour control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs 71.8%, p=0.049).r
(A) Kaplan-Meier estimates of overall survival (B) Kaplan-Meier estimates of progression-free survivalr
© New England Journal of Medicine 2010
Toxicity
Adverse events were similar in the two groups; with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups.r
Toxicityr
© New England Journal of Medicine 2010