PHASE-II TRIAL OF FLUDARABINE PHOSPHATE AND INTERFERON ALFA-2A IN ADVANCED MYCOSIS-FUNGOIDES SEZARY-SYNDROME

Purpose: This phase It study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (I FN) to fludarabine in patients with advanced or refractory mycosis fun goides (MF) or the Sezary syndrome (SS). Patients and Methods: Thirty- five patients were treated with fludarabine 25 mg/m(2) intravenously ( IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m(2) subcu taneously three times per week continuously for up to eight cycles. IF N doses were escalated to 7.5 x 10(6)/ m(2) at day 29 if constitutiona l toxicities were less than grade 3. Twenty-one patients herd not resp onded to prior chemotherapy or total-skin electron-beam irradiation (T SEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated. Results: Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). F our of 11 patients with visceral involvement responded. The median pro gression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained respo nse after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow apl asia. Eighteen patients developed infections during therapy, including five with herpes tester, one with Pneumocystis carinii, one with extr apulmonary tuberculosis, and two with disseminated toxoplasmosis. Conc lusion: The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior the rapy with DCF and IFN. This regimen has induced unmaintained remission s in a small subset of patients.