Continuous Indomethacin and Ranitidine with Interleukin-2 in Advanced Renal Carcinoma and Melanoma: A Preliminary Report

Abstract

Experimental work has shown that during the development of tumours, host macrophages can deactivate natural killer cells and suppress lymphokine-activated killer cell development, apparently through prostaglandin E2 production. Continuous indomethacin combined with interleukin (IL)-2 may totally eradicate experimental lung metastases. The preliminary results of a phase II trial of this combination are reported. Indomethacin 50 to 75 mg tid and ranitidine 150 mg bid are started at least one week before IL-2 and continued until disease progression. IL-2 is given by continuous infusion for three courses, each consisting of five days of treatment and six days of rest. IL-2 starting dose is 3.0x106 Cetus U/m2 for the first course with escalation to 4.5x106 and 6.0x106 U/m2 if toxicity allows. Pressor agents are not used. Thirty-two renal carcinoma patients were registered with seven withdrawing early. Two complete and three partial responses were seen for a response rate of (20%) for eligible and treated patients, or (16%) for all entered patients. Minor responses were seen in three patients. Twenty-five melanoma patients have been registered thus far and 18 have been eligible to proceed with IL-2 therapy. One complete and two partial responses have been seen. Two of these responses (one complete and one partial) were achieved on indomethacin and ranitidine alone, before starting IL-2.