Long-term analysis of two prospective studies that incorporate mitomycin C into an adjuvant chemoradiation regimen for pancreatic and periampullary cancers

• Published in: Advances in radiation oncology
• Main Authors: Schunke, Kathryn J., PhD, Rosati, Lauren M., BS, Zahurak, Marianna, MS, Herman, Joseph M., MD, MSc, Narang, Amol K., MD, Usach, Irina, Klein, Alison P., MHS, PhD, Yeo, Charles J., MD, Korman, Larry T., BSN, Hruban, Ralph H., MD, Cameron, John L., MD, Laheru, Daniel A., MD, Abrams, Ross A., MD
• Format: Journal Article
• Language: English
• Published: 2017
• Subjects: Hematology, Oncology, and Palliative Medicine; toxicity; Periampullary cancer; mitomycin C; pancreatic; adjuvant therapy; long-term survival
• ISSN: 2452-1094; 2452-1094
• DOI: 10.1016/j.adro.2017.07.008

Abstract Purpose To report toxicity and long-term survival outcomes of two prospective trials evaluating mitomycin C (MMC) with 5-fluorouracil-based adjuvant chemoradiation in resected periampullary adenocarcinoma. Methods From 1996 to 2002, 119 patients received an adjuvant 4-drug chemotherapy regimen of 5-fluorouracil, leucovorin, MMC, and dipyridamole with chemoradiation on two consecutive trials (Trial A and B). Trial A patients received upfront chemoradiation (50 Gy split-course , 2.5 Gy/fraction) followed by four cycles of the 4-drug chemotherapy with bolus 5-fluorouracil. Trial B patients received one cycle of the 4-drug chemotherapy with continuous infusion 5-fluorouracil followed by continuous chemoradiation (45-54 Gy, 1.8 Gy/fraction) and 2 additional cycles of chemotherapy. Cox proportional hazards models were performed to identify prognostic factors for overall survival (OS). Results Of the 62 Trial A patients, 61% had pancreatic and 39% non-pancreatic periampullary carcinomas. Trial B (n=57) consisted of 68% pancreatic and 32% non-pancreatic periampullary carcinomas. Resection margin and lymph node status were similar for both trials. Median follow-up was longer for Trial A than Trial B (197.5 vs. 107.0 months), with median OS of 32.2 and 24.2 months, respectively. Rates of 3-, 5-, and 10-year OS were 48%, 31%, and 26% in Trial A and 32%, 23%, and 9% in Trial B. On multivariate analysis, lymph node-positive resection was the strongest prognostic factor for OS. A pancreatic primary and positive margin status were also associated with inferior survival (p<0.05). Rates of grade ≥3 treatment-related toxicity in Trials A and B were 2% and 7%, respectively. Conclusions This is the first study to report long-term outcomes of MMC with 5-fluorouracil-based adjuvant chemoradiation in periampullary cancers. As MMC may be considered in DNA repair-deficient carcinomas, randomized trials are needed to determine the true benefit of adjuvant MMC.