This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miller, R. L. Articles by Urba, W. J. Search for Related Content PubMed PubMed Citation Articles by Miller, R. L. Articles by Urba, W. J.

Randomized Trial of Recombinant 2b-Interferon with or without Indomethacin in Patients with Metastatic Malignant Melanoma¹

Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, NIH, Frederick Cancer Research Facility, Frederick, Maryland 21701 [R. L. M., R. G. S., J. W. C., J. W. S., E. C., J. E. M., D. L. L.]; Clinical Immunology Services, Program Resources, Inc., NCI-Frederick Cancer Research Facility, Building 560, Room 11-62, Frederick, Maryland 21701 [W. J. U.]; Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland [M. J. H.]; and Frederick Memorial Hospital, Frederick, Maryland 21701 [M. J. J.]

-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects. The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon. We conducted a prospective randomized trial of -interferon given with or without indomethacin to patients with malignant melanoma to determine what effect, if any, indomethacin might have on the toxic, immunomodulatory, and therapeutic properties of interferon in this disease. 53 patients were stratified according to performance status and randomized to receive 2b-interferon, 20 million units per m² i.v., 5 days per week for 4 weeks followed by 10 million units per m² s.c. three times per week, either with or without indomethacin, 25 mg orally three times a day. The overall major response rate was 13% (three complete responders and three partial responders among 47 evaluable patients) and was the same on both arms. The mean maximal temperature elevation induced by interferon was significantly reduced (from 102.1 to 100.7, P = 0.0002) by indomethacin, but the incidence and severity of interferon-related fatigue, reduction in performance status, headache, depression, confusion, elevations in liver function tests, and myelosuppression were no different in either arm of the study. Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses. Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin. Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy. Immunological changes did not correlate with response status. We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities. Since fever is rarely the dose-limiting toxicity of interferon, indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study.

¹ Research sponsored, at least in part, by the National Cancer Institute, DHHS, under contract N01-CO-74102 with Program Resources, Incorporated. The contents of this publication do not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

² To whom requests for reprints should be addressed, at Program Resources, Inc., NCI-Frederick Cancer Research Facility, P. O. Box B, Building 560, Room 11–62, Frederick, MD 21701.

Received 8/15/88. Revised 12/22/88. Accepted 1/ 4/89.

This article has been cited by other articles:

				R. Dummer, C. Garbe, J. A. Thompson, A. M. Eggermont, K. Yoo, T. Maier, and B. Bergstrom Randomized Dose-Escalation Study Evaluating Peginterferon Alfa-2a in Patients With Metastatic Malignant Melanoma J. Clin. Oncol., March 1, 2006; 24(7): 1188 - 1194. [Abstract] [Full Text] [PDF]

				R. F. Kefford Adjuvant therapy of cutaneous melanoma: the interferon debate Ann. Onc., March 1, 2003; 14(3): 358 - 365. [Abstract] [Full Text] [PDF]

				P. C. Trask, P. Esper, M. Riba, and B. Redman Psychiatric Side Effects of Interferon Therapy: Prevalence, Proposed Mechanisms, and Future Directions J. Clin. Oncol., June 11, 2000; 18(11): 2316 - 2326. [Abstract] [Full Text] [PDF]