Final results of a phase III randomized controlled trial comparing modified gemcitabine + oxaliplatin (mGEMOX) to gemcitabine+ cisplatin in management of unresectable gall bladder cancer (GBC)

Background : Combination of gemcitabine and platinum (cisplatin/ oxalipatin) though standard for advanced/unresectable GBC has not been directly compared. This study was designed to see if OS with mGEMOX is equivalent to GemCis. Methods : Single center phase III randomized trial. Primary end point was OS in 2 groups. Main Secondary end points were: 1. PFS in 2 groups; 2. RR in two groups. Considering median OS of 9.5 month in mGEMOX (as per our previous study) and 11.7month in GemCis 108 patients were required in each arm to have 7 ±2 month with 80% power. To account for protocol violation and lost to follow up additional 22 patients in each arm were enrolled. Treatment protocol: Ar m A-mGEMOX Oxaliplatin 80 mg/m2 and Gemcitabine 900 mg/m2 day1 and 8 maximums of 6 cycles, Arm B- GemCis Cisplatin 25 mg/m2 Gemcitabine 1000 mg/m2 day1 and 8 maximums of 8 cycles, repeated every 3 weeks. Results : Between February 2010 and July 2015, 260 patients with unresectable/metastatic GBC subjects were randomly assigned in a 1:1 ratio to mGEMOX or GemCis. 243 patients (119 in mGEMOX and 124 in GemCis) received at least 1 dose of chemotherapy and were considered analyzable. Subjects in 2 groups were well matched for baseline characteristics. Median number of cycles was 4 in both the groups. 33.4% in mGEMOX and 25.8% in GemCis completed the assigned treatment. Median follow up of surviving patients is 10.5 months (range 4.5-47). Median OS in mGEMOX is 9 months (95% CI = 7.77-10.22) and 8 months in GemCis arm (95% CI = 7.40-8.59); p = 0.152. Median PFS in mGEMOX is 6 months (95% CI = 4.72-7.27) and 4.5 months in GemCis arm (95% CI = 3.44-5.55); p = 0.123. 29.4% (35) and 18.5% (23) patients survived 12 month or longer in mGEMOX and GemCis arms respectively (p = 0.442). 23.5% and 22.6% subjects achieved objective CR/PR in mGEMOX and GemCis arms respectively. Toxicity was comparable except more grade 3/4 diarrhea, and grade 1/2 peripheral neuropathy in mGEMOX arm. Conclusions : This study confirms that 6 cycles of mGEMOX is equivalent to 8 cycles of GemCis and one of these may be chosen for initial treatment.