PHASE-I STUDY OF TREATMENT WITH ORAL 13-CIS-RETINOIC ACID, SUBCUTANEOUS INTERFERON ALFA-2A, CISPLATIN, AND 24-HOUR INFUSION 5-FLUOROURACIL LEUCOVORIN/

A combination of oral 13-cis-retinoic acid (cis-RA) and subcutaneous i nterferon alfa-2a (IFN) has been reported to yield high response rates in patients with squamous cell carcinomas (SCCAs) of the cervix and s kin. Cisplatin and 5-fluorouracil with leucovorin (5-FU/LV) are chemot herapeutic agents commonly used for SCCAs. Purpose: To determine the m aximum tolerated doses (MTDs) of cisplatin and 5-FU/LV when combined w ith IFN and cis-RA, and to define a recommended phase II regimen for t esting in cervical cancer and other appropriate tumor types. Methods: Phase I cohort design. Cisplatin was administered every 3 weeks. 5-FU and LV were administered together as a weekly 24-h infusion. Cis-RA wa s given orally twice daily. IFN was initially given subcutaneously at a dose of 3 million units (MU) daily. Results: A total of 31 patients were treated. The IFN dose was reduced to 3 MU three times weekly beca use of patient intolerance. Cytopenias prevented the administration of weekly 5-FU/LV. Single-agent cisplatin with three times weekly IFN an d twice daily cis-RA was tolerable. Four partial responses were observ ed, in patients with adrenal cancer, bladder cancer, gastric cancer, a nd adenocarcinoma of unknown primary. Conclusions: The recommended pha se II regimen is cisplatin 100 mg/m(2) every 3 weeks, IFN 3 MU three t imes weekly, and cis-RA 1 mg/kg daily. This appears to be more toxic t han single-agent cisplatin, but the preliminary activity observed warr ants further testing.