High dose etretinate and interferon-alpha - A phase I study in squamous cell carcinomas and transitional cell carcinomas

Simultaneous exposure to retinoids and interferons can result in enhanced a ntiproliferative and differentiating effects on malignant lesions. We studi ed the toxicity and the potential efficacy of an association of high dose e tretinate and Interferon-alpha (IFN-alpha) in squamous cell carcinomas of t he lung, head and neck, the esophagus, cervix and the penis, as well as in transitional carcinomas of the bladder. The treatment consisted of etretina te (Tigason(R)) 4 mg/kg/d on 2, 3, 4 and finally 5 consecutive days every o ther week and IFN-alpha (Roferon(R)) 6 Mio IU sc, q.d. for 5 days every wee k. Of 24 patients enrolled, 23 were assessable for toxicity and 20 for resp onse. With two occurrences of grade 3 cutaneous toxicity, the administratio n of etretinate (TigasonI(R)) 4 mg/kg/d on 5 consecutive days every other w eek and IFN-alpha (Roferon(R))6 Mio IU sc, q.d. for 5 days every week was c onsidered to be the MTD. Toxicity was mild otherwise, mostly at grades 1 an d 2 level, causing fatigue, skin peeling and erythema, mucositis and cheili tis; 3 PR (partial response) and 8 SD (stable disease) were recorded. Of th e responders, one patient had become resistant to cisplatin-based chemother apy and the other two had at no lime ever received systemic therapy. We con clude that the association of high doses of etretinate and IFN-alpha has mo derate activity in squamous cell carcinomas, is well tolerated, and that IF N-alpha plays a role in the improved tolerance of the retinoid.