CLINICAL AND IN-VITRO RESPONSE TO 13-CIS-RETINOIC ACID IN INTERFERON-ALPHA RESISTANT RENAL-CELL CARCINOMA

Retinoids are known to control many important biological processes, in cluding differentiation, morphogenesis, growth and tissue homeostasis. More recently, clinical and pre-clinical results provide evidence for an antiproliferative effect of 13-cis-retinoic acid (13cRA) in interf eron-alpha (IFN-alpha) treated renal cell carcinoma patients. The mann er in which 13cRA augments antitumor effects and modulates biologic an d clinical responses of renal cell carcinoma to IFN-alpha remains elus ive. In the present study, we report induction of apoptosis and object ive tumor regression in response to 13cRA in advanced renal cell carci noma patients refractory to IFN-alpha. Among 21 patients treated there were one complete and four partial remissions (objective response rat e, 24% median response duration 8+ months). Preliminary evidence sugge sts that 13cRA acid may reverse IFN-alpha resistance in renal cell car cinoma.