A phase I-II study of 9-cis retinoic acid and interferon-alpha 2b in patients with advanced renal-cell carcinoma: An NCIC Clinical Trials Group study

Although advanced renal-cell carcinoma (RCC) responds poorly to standard th erapies, phase I-II trials have shown activity for combinations of interfer on-alpha 2b (IFN) with a retinoid. Alitretinoin (9-cis RA) is an endogenous retinoid with high binding affinity for both RAR and RXR receptor families . This phase I-II study enrolled 38 patients with RCC in a dose-escalation study of tolerability, pharmacokinetics (PK), and efficacy of twice daily o ral 9-cis RA with subcutaneous IFN. In contrast to studies with similar dos es of daily 9-cis RA, PK studies found a consistent reduction in 9-cis RA c oncentrations of about 50% after multiple b.i.d. doses of 30 or 50 mg/m(2), independent of cotreatment with IFN. In the phase I portion, toxicities in cluded systemic symptoms typical of IFN and biochemical abnormalities previ ously associated with retinoids. Two patients experienced dose-limiting tox icity at 50 mg/m(2) b.i.d. of 9-cis RA, thus the recommended phase II dose was 30 mg/m(2) b.i.d. One of twenty-six evaluable patients achieved a durab le objective partial remission, and repeated dosing with this regimen was p oorly tolerated. This combination of retinoid and interferon is not recomme nded for further study in RCC.