Impact of Chemoradiotherapy versus Chemotherapy on Operability and Survival in Patients with Locally Advanced Surgically Inoperable Pancreatic Cancer: A Randomized Trial

Abstract

Aims: To determine the tolerability and efficacy (as regards response, toxicity, resectability, progression free survival, and overall survival) of chemotherapy alone versus induction chemotherapy then concurrent 3D conformal radiotherapy. Study Design:  This was a prospective double arm study. Place and Duration of Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura and Meet Ghmmr oncology centre, Egypt, between May 2017 and June 2019. Methodology: Between May 2017 and June 2019, 58 patients with biopsy-proven localized unresectable pancreatic cancer were treated either with chemotherapy alone (n=27) or chemotherapy followed by chemoradiotherapy (n=31). Radiation therapy was delivered with a dose of 50.4 Gy in a single fraction of 1.8 Gy using 3D conformal radiotherapy and concurrent CT was typically given with capecitabine at a dose of 825 mg/m2 twice daily orally from Saturday to Wednesday throughout the whole course of radiotherapy. They received induction chemotherapy gemcitabine-cisplatin in arm I (6 cycles) and arm II (4 cycles), {gemcitabine dose of 1000 mg/m2, cisplatin dose of 50 mg/m2D1+D15 every 4 weeks}. Surgery was done for responders. Results: Overall response rate was 66.7% & 96.8% in chemotherapy and chemoradiotherapy groups respectively with statistically significant difference; no complete was achieved (P=0.004). Four patients (14.8 %) in group1and ten patients (31.25%) in group 2 became resectable with no statistical significant difference between both groups (P=0.121). No statistically significant difference in the occurrence of toxicities between the two groups except for diarrhea and stomatitis that were significantly higher in chemoradiotherapy group. There were no reported grade 4 toxicities. The median follow-up time was 18 months. Median progression free survival was statistically significant and higher in chemoradiotherapy group than in chemotherapy group (12 & 9 months respectively); P = 0.024. Median overall survival was higher but not statistically significant in chemoradiotherapy (22 months) versus 14 months in chemotherapy group; P = 0.054. Conclusion: concurrent chemoradiotherapy using capecitabine and 3D conformal radiotherapy with initial systemic gemcitabine plus cisplatin is tolerable, effective and offers good local control for patients with locally advanced pancreatic cancer. This protocol showed a significantly better overall response and progression free survival but no overall survival benefit.