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. 2017 Aug 3;3(1):42-51.
doi: 10.1016/j.adro.2017.07.008. eCollection 2018 Jan-Mar.

Long-term analysis of 2 prospective studies that incorporate mitomycin C into an adjuvant chemoradiation regimen for pancreatic and periampullary cancers

Kathryn J Schunke  1   2 , Lauren M Rosati  1 , Marianna Zahurak  3 , Joseph M Herman  1 , Amol K Narang  1 , Irina Usach  4 , Alison P Klein  4 , Charles J Yeo  5 , Larry T Korman  1 , Ralph H Hruban  6 , John L Cameron  7 , Daniel A Laheru  4 , Ross A Abrams  1   8
Affiliations

Long-term analysis of 2 prospective studies that incorporate mitomycin C into an adjuvant chemoradiation regimen for pancreatic and periampullary cancers

Kathryn J Schunke et al. Adv Radiat Oncol. .

Abstract

Purpose: The purpose of this study was to report toxicity and long-term survival outcomes of 2 prospective trials evaluating mitomycin C (MMC) with 5-fluorouracil-based adjuvant chemoradiation in resected periampullary adenocarcinoma.

Methods and materials: From 1996 to 2002, 119 patients received an adjuvant 4-drug chemotherapy regimen of 5-fluorouracil, leucovorin, MMC, and dipyridamole with chemoradiation on 2 consecutive trials (trials A and B). Trial A patients received upfront chemoradiation (50 Gy split-course, 2.5 Gy/fraction) followed by 4 cycles of the 4-drug chemotherapy with bolus 5-fluorouracil. Trial B patients received 1 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% nonpancreatic periampullary carcinomas. Trial B (n = 57) consisted of 68% pancreatic and 32% nonpancreatic 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 < .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. Because MMC may be considered in DNA repair-deficient carcinomas, randomized trials are needed to determine the true benefit of adjuvant MMC.

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Figures

Figure 1
Figure 1
Kaplan-Meier overall survival curve of all patients separated by trial A versus trial B.
Figure 2
Figure 2
Kaplan-Meier overall survival curve of (A) trial A and (B) trial B patients separated by a PDAC versus non-PDAC diagnosis. Med, median; PDAC, pancreatic ductal adenocarcinoma.
See this image and copyright information in PMC

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