Int. J. Radiation Oncology Biol. Phys., Vol. 35. No. 2, pp. 299-303, 1996 Copyright 0 1996 Elsevier Science Inc. Printed in the USA. All rights reserved 0360.3016/96 %15.00 + .OO PII: SO360-3016(96)00016-8 l Clinical Original Contribution OLSALAZINE IS CONTRAINDICATED DURING PELVIC RADIATION THERAPY: RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL JAMES A. MARTENSON,JR., M.D., * GLENN HYLAND, M.D., + CHARLES G. MOERTEL, M.D.,* JAMES A. MAILLIARD, M.D., $ JUDITH R. O'FALLON, PH.D., * ROGER T. COLLINS, M.D.,8 ROSCOE F. MORTON, M.D.,# HAMED H. TEWK, M.D., n RANDY L. MOORE, D.O., * * ALBERT R. FRANK, M.D., $ RODOLFO E. URIAS, M.D. a AND RICHARD L. DEMING, M.D.# *Mayo Clinic and Mayo Foundation, Rochester, MN; ‘Quain and Ramstad Clinic, Bismarck, ND; *Nebraska Oncology Group- Creighton University, University of Nebraska Medical Center, and Associates, Omaha, NE; “Duluth Community Clinical Oncology Program, Duluth, MN; ‘Iowa Oncology Research Association CCOP, Des Moines, IA; “Cedar Rapids Oncology Project CCOP, Cedar Rapids, IA; and * *Meritcare Hospital CCOP, Fargo, ND Purpose: A randomized clinical trial from Great Britain suggested a possible beneficial effect of acetylsalicy- -in prevention of radiation-induced bowel toxicity. Olsalazine is an orally administered drug designed to deliver 5aminosalicylate to the large bowel with minimal systemic absorption. A randomized clinical trial was undertaken to assess the effectiveness of olsalazine in preventing acute diarrhea in patients receiving pelvic radiation therapy. Methods and Materials: Patients receiving pelvic radiation therapy were randomized, in double-blind fashion, to olsalazine 250 mg, two capsules twice daily, or an identical appearing placebo, two capsules twice daily. Patients were then evaluated weekly during radiation therapy for the primary study endpoint, diarrhea, as well as rectal bleeding, abdominal cramping, and tenesmus. Results: The study was closed early, after entry of 58 evaluable patients, when a preliminary analysis showed excessive diarrhea in patients randomized to olsalazine. The incidence and severity of diarrhea were worse in patients randomized to olsalazine @ = 0.0036). Sixty percent of the patients randomized to olsalazine experienced Grade 3 or 4 diarrhea compared to only 14% randomized to placebo. There was also a trend toward higher incidence and greater severity of abdominal cramping in patients who were randomized to olsahuine (p = 0.084). Conclusion: Administration of olsalazine during pelvic radiation therapy resulted in an increased incidence and severity of diarrhea. Olsalazine is contraindicated in patients receiving pelvic radiation therapy. Olsalazine, Pelvic radiation therapy, Adverse effects. INTRODUCTION Pelvic radiation therapy is used in a wide variety of clini- cal settings as either adjuvant or primary treatment for patients with gastrointestinal, gynecologic, genitourinary, and other malignancies. Radiation bowel toxicity, mani- fested primarily by increased stool frequency, represents the major type of acute toxic reaction for these patients. An effective medical regimen for preventing symptoms of acute radiation bowel toxicity would be useful in pa- tients with a broad range of malignancies in which pelvic radiation therapy has a role. From the observation that administration of certain prostaglandins results in diarrhea ( 1, 4, 8), Mennie et al. (7) hypothesized that prostaglandin release might be an etiologic factor in radiation-induced diarrhea. They under- Presented at the annual meeting of the American Society for Clinical Oncology, Los Angeles, CA, 21 May 1995. Reprint requests to: James A. Martenson, Jr., M.D., Mayo Clinic, 200 First Street SW, Rochester, MN, 55905. Acknowledgements-This study was conducted as a collabora- tive trial of North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service Grants CA-25224, CA-37404, CA-15083, CA-35269, CA- 35101, CA-52352, CA-37417, CA-35272, and CA-35103 from the National Cancer Institute, Department of Health and Human Services. Additional participating institutions include: Grand Forks Clinic, Ltd., Grand Forks, ND 58201 (John A. Laurie, M.D.) ; Ochsner Community Clinical Oncology Program, New Orleans, LA 70121 (Carl G. Kardinal, M.D.): Siouxland Hema- tology-Oncology Associates, Sioux City, IA 5 1105 (John C. Michalak, M.D.); and Sioux Community Cancer Consortium, Sioux Falls, SD 57105 (Loren K. Tschetter, M.D.). Accepted for publication 29 December 1995. 299