Combination of chemotherapy and recombinant alpha-interferon in advanced non-small cell lung cancer: Multicentric randomized FONICAP trial report

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Abstract
Background. Preclinical data suggested that alphainterferon (IFN) may potentiate chemotherapy cytotoxicity. Methods. A prospective multicentric randomized trial was initiated to assess the clinical benefit of adding recombinant alpha‐2‐IFN to combination chemotherapy in patients with metastatic non‐small cell lung cancer. A total of 182 patients were randomized to receive either cisplatin‐epidoxorubicin‐cyclophosphamide (CEP) combination chemotherapy (cisplatin, 60 mg/m2; epidoxorubicin, 50 mg/m2; and cyclophosphamide, 400 mg/m2 intravenously) alone on day 1 or the same chemotherapy plus recombinant alpha‐2‐IFN at the dose of 5 MU intramuscularly from day – 2 to +4, then 3 times weekly. Results. The median survival was 6 months in the CEP plus IFN arm versus 5.5 months in the control arm. The log‐rank test showed a marginal statistically significant difference (P = 0.045) in favor of CEP chemotherapy, which disappeared when survival curves were adjusted for prognostic factors. Progression‐free survival was similar in the two treatment arms. Considering all eligible patients, the response rate was 7.6% in the CEP arm versus 18.9% in the CEP plus IFN arm (P = 0.042). Nearly 40% of the patients receiving IFN had grade 3–4 nadir leukopenia versus 15% in the control arm (P = 0.01) and 12.5% versus 4.2% had grade 3–4 thrombocytopenia. Apart from the usual constitutional symptoms, IFN was also responsible for increased emesis and mucositis. Conclusions. This study indicates that the addition of recombinant alpha‐IFN to CEP chemotherapy can increase response rate and toxicity to treatment without a positive effect on progression‐free survival and survival.