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

Experimental work has shown that during the development of tumours,host macrophages can deactivate natural killer cells and suppress lymphokine-activated killer celldevelopment, apparently through prostaglandin E2 production. Continuous indomethacin combined withinterleukin (IL)-2 may totally eradicate experimental lung metastases. The preliminary results of a phaseII trial of this combination are reported. Indomethacin 50 to 75 mg tid and ranitidine 150 mg bid are startedat least one week before IL-2 and continued until disease progression. IL-2 is given by continuous infusionfor three courses, each consisting of five days of treatment and six days of rest. IL-2 starting dose is 3.0x106Cetus U/m2 for the first course with escalation to 4.5x106 and 6.0x106 U/m2 if toxicity allows. Pressoragents 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 treatedpatients, or (16%) for all entered patients. Minor responses were seen in three patients. Twenty-fivemelanoma 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 onepartial) were achieved on indomethacin and ranitidine alone, before starting IL-2