COMBINATION OF CISPLATIN AND INTERFERON-ALPHA-2A (ROFERON(R)-A) IN PATIENTS WITH NONSMALL CELL LUNG-CANCER (NSCLC) - AN OPEN PHASE-II MULTICENTER STUDY

Preclinical and preliminary clinical data suggested a potentiation of the cytotoxic activity of cisplatin (CDDP) by interferon-alpha (IFN-al pha) in non-small cell lung cancer (NSCLC). This open, non-randomised, phase II study was set up to determine the response rate, duration of response, survival, safety and tolerability following treatment with the combination of recombinant IFN-alpha 2a and CDDP in NSCLC. 100 pre viously untreated patients with unresectable, measurable or evaluable stage III/IV NSCLC were enrolled for treatment with a combination of I FN-alpha 2a (9 MIU three times weekly) and CDDP (100 mg/m(2) every 28 days). Patients were stratified according to histology, i.e. squamous cell carcinoma versus non-squamous cell carcinoma. The planned maximum treatment duration was 6 months or until disease progression. Respond ing patients could be treated with IFN-alpha 2a as maintenance for an additional 6 months. To be evaluable, the patients must have received at least 2 weeks of treatment with IFN-alpha 2a and at least one dose of CDDP. There were 75% male and 25% female patients with a mean age o f 59 years (range 34-74). An overall response rate of 33% (95% confide nce interval (C.I.) = 23-44) was achieved among the 84 evaluable patie nts. There was one complete responder and 27 partial responders, while 32 patients had stable disease. The duration of partial response rang ed from 3 to 12 months. The median survival was 6.4 (95% C.I, = 5.7-8) months. The response rate in patients with stage IIIa disease (45%) w as significantly higher (P = 0.047) than in patients with stage IV dis ease (22%). The median survival in patients with stage IIIa disease (9 .3 months) was significantly longer (P = 0.025) than patients with eit her stage IIIb (6.3 months) or stage IV disease (6.2 months). The majo r forms of toxicity were gastrointestinal and constitutional symptoms of mild to moderate severity. The main severe adverse events (WHO grad e 3-4) were nausea and vomiting (32%), anorexia (16%) and fever (11%). The most frequent severe haematological toxicities (WHO grade 3-4) we re neutropenia (27%), anaemia (18%) and thrombocytopenia (10%). 13 pat ients experienced WHO grade 3-4 renal toxicity. This study confirms th e antitumour activity of the combination of IFN-alpha 2a and CHOP in N SCLC. Further study of this combination is warranted.