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

Kathryn J. Schunke, PhD; Lauren M. Rosati, BS; Marianna Zahurak, MS; Joseph M. Herman, MD, MSc; Amol K. Narang, MD; Irina Usach; Alison P. Klein, MHS, PhD; Charles J. Yeo, MD; Larry T. Korman, BSN; Ralph H. Hruban, MD; John L. Cameron, MD; Daniel A. Laheru, MD; Ross A. Abrams, MD

doi:10.1016/j.adro.2017.07.008

Advances in Radiation Oncology (Jan 2018)

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

Kathryn J. Schunke, PhD,
Lauren M. Rosati, BS,
Marianna Zahurak, MS,
Joseph M. Herman, MD, MSc,
Amol K. Narang, MD,
Irina Usach,
Alison P. Klein, MHS, PhD,
Charles J. Yeo, MD,
Larry T. Korman, BSN,
Ralph H. Hruban, MD,
John L. Cameron, MD,
Daniel A. Laheru, MD,
Ross A. Abrams, MD

Affiliations

Kathryn J. Schunke, PhD: Department of Radiation Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Lauren M. Rosati, BS: Department of Radiation Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Marianna Zahurak, MS: Division of Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland
Joseph M. Herman, MD, MSc: Department of Radiation Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Amol K. Narang, MD: Department of Radiation Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Irina Usach: Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Alison P. Klein, MHS, PhD: Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Charles J. Yeo, MD: Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
Larry T. Korman, BSN: Department of Radiation Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Ralph H. Hruban, MD: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
John L. Cameron, MD: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Daniel A. Laheru, MD: Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
Ross A. Abrams, MD: Department of Radiation Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland

DOI: https://doi.org/10.1016/j.adro.2017.07.008
Journal volume & issue: Vol. 3, no. 1
pp. 42 – 51

Abstract

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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.

Published in Advances in Radiation Oncology

ISSN: 2452-1094 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General): Medical physics. Medical radiology. Nuclear medicine; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/advances-in-radiation-oncology/

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