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Sustained oral indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced renal cell carcinoma



Sustained oral indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced renal cell carcinoma



Cancer BioTherapy 8(3): 229-233



Experimental work in murine models has shown that, during the development of tumors, prostaglandin E-2 produced by host macrophages inactivates natural killer cells and suppresses lymphokine-activated killer (LAK) cell development. Chronic indomethacin therapy when combined with interleukin-2 (IL-2) can totally eradicate experimental lung metastases in these models. A phase II trial was performed to study the clinical efficacy of chronic indomethacin and intermittent IL-2 therapy in patients with advanced renal cell carcinoma. Patients were placed on indomethacin and ranitidine orally at least one week prior to commencing therapy with IL-2. IL-2 was given by continuous infusion for three courses, each consisting of 5 days of treatment with 6 days of rest. Initial dose of IL-2 was 18.0 times 10-6 IU/m-2/day for the first course with escalation to 27.0 times 10-6 IU/m-2/day for the second and 36.0 times 10-6 IU/m-2/day for the third course, if toxicity allowed. Patients were admitted to a general oncology ward for therapy with IL-2, and vasopressor agents were not used. Thirty-two patients were eligible, with 7 patients withdrawing early from the study. Twenty-five patients went on to receive at least one course of IL-2. Two complete and three partial responses were seen for an objective response rate of 5/25 (20%) for eligible and treated patients or 5/32 (16%) for all patients entered onto the study, regardless of treatment status. The response rate to this regimen is comparable with other high dose IL-2 regimens in renal cell carcinoma, including those employing adoptive therapy with lymphokine-activated killer cells.

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Accession: 009498827

Download citation: RISBibTeXText

PMID: 7804363

DOI: 10.1089/cbr.1993.8.229


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