PHASE-II TRIAL OF RECOMBINANT IFN-ALPHA-2A WITH ETOPOSIDE CISPLATIN INDUCTION AND INTERFERON/MEGESTROL ACETATE MAINTENANCE IN EXTENSIVE SMALL-CELL LUNG-CANCER/

Previous data suggested interaction of cisplatin with interferon (IFN) in non-small cell lung cancer and a possible effect of IFN in maintai ning remission in small cell lung cancer (SCLC). This study was design ed to further examine the effect of IFN in the treatment of extensive disease (ED) SCLC. Forty previously untreated patients with performanc e status (PS) of 0-2 (Zubrod scale) were treated with etoposide (100 m g/m(2) for 3 days), cisplatin (25 mg/m(2) for 3 days) (EP), and recomb inant IFN-alpha 2a (rIFN-alpha 2a) (5 x 10(6) U/m(2) for 3 days) for s ix cycles (induction), followed by rIFN-alpha 2a (5 x 10(6) U/m(2)) th rice weekly and megestrol acetate (40 mg qid) as maintenance therapy f or 6 months or until progressive disease or intolerable toxicity was d ocumented. Patients were 25 men (62%) and 15 women (38%), median age 5 8 (28-76), median Zubrod performance status 1 (0-2). Major sites of me tastasis include liver (55%), bone (42%), bone marrow (25%), and adren al gland (18%). Of 40 eligible patients accrued to this trial, 35 were evaluable for response, and 37 were evaluable for toxicity. There wer e 3 complete and 28 partial responses, for an overall response rate of 89%. With 39 of 40 patients followed until death, median survival (Ka plan-Meier) is estimated at 46 weeks (95% CI range 35-55). Twenty pati ents completed six cycles of induction, and 16 received maintenance th erapy, median 2 cycles (range 1-3). Major toxicity during induction in cluded grade 4 granulocytopenia in 24%, grade 2-3 nausea or vomiting o r both in 41%, grade 2 fatigue in 24%, grade 2 anorexia in 22%, and gr ade 2-3 renal insufficiency in 9% of 175 total courses of chemotherapy administered. Toxicity during the maintenance phase was notable for g rade 2-3 fatigue in 43%, grade 2-3 anorexia in 24%, grade 2-3 weight l oss in 10%, and grade 3-4 anemia in 17% of 30 courses. There were no t reatment-related deaths. The addition of rIFN-alpha 2a to EP in induct ion chemotherapy of ED SCLC, followed by rIFN-alpha 2a and megestrol a cetate maintenance therapy, was reasonably well tolerated. The complet e and overall response rates and duration of remission and survival ap pear to be similar to those generally obtained with EP alone in simila r patients.