Atul Sharma1, Bidhu Kalyan Mohanti2, Surendra Pal Chaudhary3, V Sreenivas4, Ranjit Kumar Sahoo5, Nootan Kumar Shukla6, Sanjay Thulkar7, Sujoy Pal8, Surya V Deo9, Sushmita Pathy10, Nihar Ranjan Dash11, Sunil Kumar12, Sushma Bhatnagar13, Rakesh Kumar14, Seema Mishra15, Peush Sahni16, Venkateswaran K Iyer17, Vinod Raina18. 1. Department of Medical Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: Atul1@hotmail.com. 2. Department of Radiation Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: drbkmohanti@gmail.com. 3. Department of Medical Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: Drsurendra101@gmail.com. 4. Department of Biostatistics, AIIMS, New Delhi 110029, India. Electronic address: sreevishnubhatla@gmail.com. 5. Department of Medical Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: drranjitmd@gmail.com. 6. Department of Surgical Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: Nkshukla2@yahoo.com. 7. Department of Radio Diagnosis, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: sanjaythulkar@gmail.com. 8. Department of Gastrointestinal Surgery and Liver Transplantation, AIIMS, New Delhi 110029, India. Electronic address: sujoypal@hotmail.com. 9. Department of Surgical Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: svsdeo@yahoo.co.in. 10. Department of Radiation Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: drspathy@gmail.com. 11. Department of Gastrointestinal Surgery and Liver Transplantation, AIIMS, New Delhi 110029, India. Electronic address: nagranjan@gmail.com. 12. Department of Surgical Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: Dr_sunilk@hotmail.com. 13. Department of Onco-anaesthesia and Palliative Medicine, Dr BRA IRCH, AIIMS, New Delhi, 110029, India. Electronic address: sushmabhatnagar1@gmail.com. 14. Professor Department of Nuclear Medicine, AIIMS, New Delhi, 110029, India. Electronic address: rkphulia@yahoo.com. 15. Professor Department of Nuclear Medicine, AIIMS, New Delhi, 110029, India. Electronic address: seemamishra2003@gmail.com. 16. Department of Gastrointestinal Surgery and Liver Transplantation, AIIMS, New Delhi 110029, India. Electronic address: peush_sahni@hotmail.com. 17. Department of Pathology, AIIMS, New Delhi 110029, India. Electronic address: iyervenkat4@gmail.com. 18. Department of Medical Oncology, Dr BRA IRCH, AIIMS, New Delhi 110029, India. Electronic address: vinodraina@hotmail.com.
Abstract
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.
RCT Entities:
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.
Authors: Christian Möhring; Jan Feder; Raphael U Mohr; Farsaneh Sadeghlar; Alexandra Bartels; Robert Mahn; Taotao Zhou; Milka Marinova; Georg Feldmann; Peter Brossart; Martin von Websky; Hanno Matthaei; Steffen Manekeller; Tim Glowka; Jörg C Kalff; Tobias J Weismüller; Christian P Strassburg; Maria A Gonzalez-Carmona Journal: Front Oncol Date: 2021-11-10 Impact factor: 6.244