AIM To determine equivalence of modified gemcitabine and oxaliplatin compared with gemcitabine and cisplatin in unresectable gallbladder cancer (GBC). Primary end-point was overall survival (OS). METHODS Open label, prospective, randomised phase III equivalence study. Inclusion criteria included histologically proven unresectable GBC, 18 years or older, adequate organ functions and Eastern Cooperative Oncology Group ≤2. SAMPLE SIZE 108 patients were required in each arm to have an equivalence margin of ±2 months with power of 80%. TREATMENT Modified gemcitabine and oxaliplatin (mGemOx)-gemcitabine 900 mg/m2, oxaliplatin 80 mg/m2, maximum 6 cycles; gemcitabine + cisplatin (CisGem)-gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, maximum 8 cycles, all day 1 and 8 every 3 weeks. RESULTS Two hundred sixty subjects were recruited between February 2011 and July 2015. Two hundred forty-three patients (119, mGemOx and 124, CisGem) received at least 1 dose and analysed for safety and efficacy (modified intention to treat). Median OS was 8·5 months for whole group (95% confidence interval [CI]: 7·9-9·1). Median OS in mGemOx was 9 months and 8·3 months in CisGem; p = 0·057 (hazard ratio = 0·78; 95% CI = 0·60-1·02). Restricted mean OS for follow-up limited to 30 months was 11·2 months (95% CI: 9·8-12·6) in mGemOx and 10·4 months (95% CI: 9·1-11·7) in CisGem. Difference of the mean was 0·8 months with 95% CI, exceeding 2 months (-1·1 to 2·7), hence rejecting equivalence. Peripheral neuropathy, thrombocytopaenia in mGemOx and nephrotoxicity was higher with CisGem. CONCLUSION This trial failed to show equivalence of eight cycles of CisGem to six cycles of mGemOx. Numerically OS was better with mGemOx. Toxicities were different. The trial was not powered to answer superiority. CLINICAL TRIAL REGISTRATION CTRI/2010/091/001406.

中文翻译：

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不可切除的胆囊癌中吉西他滨和奥沙利铂或吉西他滨+顺铂的修饰：III期随机对照试验的结果。

目的确定不可切除的胆囊癌（GBC）与吉西他滨和顺铂相比，吉西他滨和奥沙利铂的等效性。主要终点是总体生存期（OS）。方法开放标签，前瞻性，随机III期等效性研究。入选标准包括组织学证明不可切除的GBC，18岁或更早，器官功能良好以及东部合作肿瘤小组≤2。样本大小每组中需要108名患者的等效范围为±2个月，功效为80％。治疗修饰的吉西他滨和奥沙利铂（mGemOx）-吉西他滨900 mg / m2，奥沙利铂80 mg / m2，最多6个周期；吉西他滨+顺铂（CisGem）-吉西他滨1000 mg / m2，顺铂25 mg / m2，最多8个周期，每3周第1天和第8天。结果在2011年2月至2015年7月之间招募了260名受试者。243名患者（119名，mGemOx和124名，CisGem）接受了至少1剂剂量，并进行了安全性和有效性分析（改良的治疗意向）。整个组的OS中位数为8·5个月（95％置信区间[CI]：7·9-9·1）。在CisGem中，mGemOx中的OS中位数为9个月和8·3个月。p ＝ 0·057（危险比＝ 0·78； 95％CI ＝ 0·60-1·02）。限制在30个月以内的随访平均OS在mGemOx中为11·2个月（95％CI：9·8-12·6），在10个月内为10·4个月（95％CI：9·1-11·7）。 CisGem。平均差为0·8个月，CI为95％，超过2个月（-1·1到2·7），因此拒绝当量。CisGem可使周围神经病变，mGemOx中的血小板减少和肾毒性更高。结论该试验未能显示8个周期的CisGem与6个周期的mGemOx的等效性。在数值上，使用mGemOx时OS更好。毒性不同。该审判无权回答优越性。临床试验注册CTRI / 2010/091/001406。