Sustained oral indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced renal cell carcinoma.
Experimental work in murine models has shown that, during the development of tumors, prostaglandin E2 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 x 10(6) IU/m2/day for the first course with escalation to 27.0 x 10(6) IU/m2/day for the second and 36.0 x 10(6) IU/m2/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.
Mertens
W C
WC
Department of Medical Oncology, London Regional Cancer Centre, Ontario, Canada.
Bramwell
V H
VH
Banerjee
D
D
Gwadry-Sridhar
F
F
al-Mutter
N
N
Parhar
R S
RS
Lala
P K
PK
D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000008:administration & dosage*
D007376:Interleukin-2; D011899:Ranitidine; D007213:Indomethacin