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Cohen SJ , Dobelbower Jr R , Lipsitz S , Catalano PJ , Sischy B , Smith TJ , Haller DG
A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282
International Journal of Radiation Oncology Biology Physics. 2005 ;62(5) :1345-1350
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Purpose: The median survival time of patients with locally advanced adenocarcinoma of the pancreas is 8-10 months. Radiation therapy has been used to improve local control and palliate symptoms. This randomized study was undertaken to determine whether the addition of 5-fluorouracil (5-FU) and mitomycin-C (MMC) to radiation therapy improves outcome in this patient population. Patients and Methods: One hundred fourteen patients were randomized to receive 59.4 Gy external beam radiotherapy in 1.8 Gy fractions alone or in combination with 5-FU (1,000 mg/m2/day for 4 days by continuous infusion Days 2-5 and 28-31) and MMC (10 mg/m2 on Day 2). Results: One hundred four patients were evaluable for efficacy. Hematologic and nonhematologic toxicities were more common in the combination arm. The response rates were 6% in the radiation therapy arm and 9% in the combination arm. There were no differences in median disease-free survival time (DFS) or overall survival time (OS) between the combination and radiation therapy alone arms: 5.1 vs. 5.0 months, respectively, for DFS (p = 0.19) and 8.4 vs. 7.1 months, respectively, for OS (p = 0.16). Conclusion: The addition of 5-FU and MMC to radiotherapy increased toxicity without improving DFS or OS in patients with locally advanced pancreatic cancer. Alternative drugs for radiosensitization may improve outcome. © 2005 Elsevier Inc.
03603016 (ISSN) Cited By: 2; Export Date: 25 May 2006; Source: Scopus CODEN: IOBPD; DOI: 10.1016/j.ijrobp.2004.12.074 Language of Original Document: English Correspondence Address: Cohen, S.J.; Department of Medical Oncology; Fox Chase Cancer Center; 333 Cottman Avenue Philadelphia, PA 19111-2497, United States; email: S_Cohen@fccc.edu Chemicals/CAS: fluorouracil, 51-21-8; mitomycin C, 50-07-7, 74349-48-7, Antineoplastic Combined Chemotherapy Protocols; Fluorouracil, 51-21-8; Mitomycin, 50-07-7 References: Jemal, A., Tiwari, R.C., Murray, T., Cancer statistics, 2004 (2004) CA Cancer J Clin, 54, pp. 8-29; Burris, H.A., Moore, M.J., Andersen, J., Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial (1997) J Clin Oncol, 15, p. 2403; Cohen, S.J., Pinover, W.H., Watson, J.C., Pancreatic cancer (2000) Curr Treat Options Oncol, 1, p. 375; Moertel, C.G., Reitemeier, R.J., Hahn, R.G., Mitomycin-C therapy in advanced gastrointestinal cancer (1968) JAMA, 204, pp. 1045-1048; Buroker, T., Kim, P.N., Groppe, C., 5-FU infusion with mitomycin-C vs. 5 FU infusion with methyl-CCNU in the treatment of advanced upper gastrointestinal cancer: A Southwest Oncology Group study (1979) Cancer, 44, pp. 1215-1221; Byfield, J.E., Barone, R., Mendelsohn, J., Infusional 5-FU and X-ray therapy for nonresectable esophageal cancer (1980) Cancer, 45, pp. 703-708; Sischy, B., Remington, J.H., Sobel, S.H., Treatment of carcinoma of the rectum and squamous carcinoma of the anus by combination chemotherapy, radiotherapy and operation (1980) Surg Gynecol Obstet, 151, pp. 369-371; Haslam, J.B., Cavanaugh, P.G., Stroup, S.L., Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas (1973) Cancer, 32, pp. 1341-1345; Childs, D.S., Moertel, C.G., Holbrook, M., Treatment of malignant neoplasms of the gastrointestinal tract with a combination of 5-fluorouracil and radiation. a randomized double-blind study (1965) Radiology, 84, pp. 843-848; Nigro, N.D., Seydel, H.G., Considine, B., Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal (1983) Cancer, 51, pp. 1826-1829; Franklin, R., Steiger, Z., Vaishampayan, G., Combined modality therapy for esophageal squamous cell carcinoma (1983) Cancer, 51, pp. 1062-1071; Miller, A.B., Hogestraeten, B., Staquet, M., Winkler, A., Reporting results of cancer treatment (1981) Cancer, 47, pp. 207-214; Oken, M.M., Creech, R.H., Tormey, D.C., Toxicity and response criteria of the Eastern Cooperative Oncology Group (1982) Am J Clin Oncol, 5, pp. 649-655; Kaplan, E.L., Meier, P., Nonparametric estimation from incomplete observations (1958) J Am Stat Assoc, 53, pp. 547-581; Moertel, C.G., Frytak, S., Hahn, Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil (1981) Cancer, 48, pp. 1705-1710, The Gastrointestinal Tumor Study Group R.G.; Treatment of locally unresectable carcinoma of the pancreas: Comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone (1988) J Natl Cancer Inst, 80, pp. 751-755, Gastrointestinal Tumor Study Group; Klaassen, D.J., MacIntyre, J.M., Catton, G.E., Treatment of locally unresectable cancer of the stomach and pancreas: A randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil - An Eastern Cooperative Oncology Group study (1985) J Clin Oncol, 3, pp. 373-378; Neoptolemos, J.P., Stocken, D.D., Friess, H., A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer (2004) N Engl J Med, 350, pp. 1200-1210; Berlin, J.D., Catalano, P., Thomas, J.P., Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297 (2002) J Clin Oncol, 20, pp. 3270-3275; Lawrence, T.S., Chang, E.Y., Hahn, T.M., Radiosensitization of pancreatic cancer cells by 2?,2?- difluoro-2?-deoxycytidine (1996) Int J Radiat Oncol Biol Phys, 34, pp. 867-872; McGinn, C.J., Zalupski, M.M., Shureiqi, I., Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer (2001) J Clin Oncol, 19, pp. 4202-4208.