Combination of cisplatin and interferon-alpha 2a (Roferon-A) in patients with non-small cell lung cancer (NSCLC). An open phase II multicentre study.

Preclinical and preliminary clinical data suggested a potentiation of the cytotoxic activity of cisplatin (CDDP) by interferon-alpha (IFN-alpha) 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 previously untreated patients with unresectable, measurable or evaluable stage III/IV NSCLC were enrolled for treatment with a combination of IFN-alpha 2a (9 MIU three times weekly) and CDDP (100 mg/m2 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. Responding 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 of 59 years (range 34-74). An overall response rate of 33% (95% confidence interval (C.I.) = 23-44) was achieved among the 84 evaluable patients. There was one complete responder and 27 partial responders, while 32 patients had stable disease. The duration of partial response ranged 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%) was significantly higher (P = 0.047) than in patients with stage IV disease (22%). The median survival in patients with stage IIIa disease (9.3 months) was significantly longer (P = 0.025) than patients with either stage IIIb (6.3 months) or stage IV disease (6.2 months). The major forms of toxicity were gastrointestinal and constitutional symptoms of mild to moderate severity. The main severe adverse events (WHO grade 3-4) were nausea and vomiting (32%), anorexia (16%) and fever (11%). The most frequent severe haematological toxicities (WHO grade 3-4) were neutropenia (27%), anaemia (18%) and thrombocytopenia (10%). 13 patients experienced WHO grade 3-4 renal toxicity. This study confirms the antitumor activity of the combination of IFN-alpha 2a and CDDP in NSCLC. Further study of this combination is warranted.