title: Interferons combined with chemotherapy in the treatment of stage III-IV non-small cell lung cancer--a randomised study.
abstract: 80 patients with previously untreated stage III-IV non-small cell lung cancer (NSCLC) were randomly assigned to receive chemotherapy (CT) alone (arm I: 26 patients) or the same CT combined with either interferon (IFN)-gamma (arm II: 27 patients) or with both IFN-gamma and IFN-alpha (arm III: 27 patients). The CT comprised cisplatin 60 mg/m2 intravenously (i.v.) day 1 and etoposide 100 mg/m2 i.v. days 1, 3 and 5, once every 28 days; the IFN therapy comprised either recombinant IFN-gamma 1b 0.2 mg/m2, subcutaneously, three times a week until day 25, or recombinant IFN-alpha 2c 6 x 10(6) U given according to the same schedule, and simultaneously with IFN-gamma. A maximum of six cycles were given. The treatment was discontinued if progressive disease (PD) was demonstrated. The mean numbers of cycles per patient given in the different arms were 3.6 (arm I), 3.0 (arm II) and 2.9 (arm III). The main reason for discontinuation in all arms was PD. 17 (28%) of the 61 evaluable patients achieved partial responses (35% in arm I, 29% in arm II and 35% in arm III, non-significant). No complete response was recorded. Haematological toxicity was dose-limiting in all arms: leucopenia (WHO grade 3) was observed universally, but more frequently in arm III (in 18% of cycles given). Only two episodes of grade 4 leucopenia were seen (arms II and III) and six episodes of grade 3-4 thrombocytopenia (arm III). Median survival was 6-7 months in all arms. The survival curve for arm II was slightly more favourable (non-significant) than those for other arms. The addition of IFN-gamma alone or IFN-alpha plus IFN-gamma to platinum-based CT did not improve response rates nor did it produce any significant survival benefit for patients with NSCLC. Increased haematological toxicity was observed when both IFNs were administered concomitantly with CT.
authors.affiliation: Department of Pulmonary Medicine, Helsinki University Central Hospital, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Halme
authors.forename: P K
authors.initials: PK
authors.lastname: Maasilta
authors.forename: S O
authors.initials: SO
authors.lastname: Pyrhönen
authors.forename: K V
authors.initials: KV
authors.lastname: Mattson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins; D005047:Etoposide; D007371:Interferon-gamma; D002945:Cisplatin