MITOMYCIN-C, VINORELBINE, CARBOPLATIN PLUS GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR FOR TREATMENT OF ADVANCED NONSMALL CELL LUNG-CARCINOMA

Background: The therapeutic potential of chemotherapy in the treatment of recurrent or metastatic non-small cell lung carcinoma (NSCLC) seem s modest. Thus, the search for novel agents and combination regimens w ith a superior therapeutic index has a high priority. The present comb ination regimen consisting of mitomycin C, vinorelbine, carboplatin an d granulocyte-macrophage colony-stimulating factor (GM-CSF) was chosen because of the known activity of these agents in NSCLC and their pote ntial drug synergism without (nonhematologic) cross-toxicity. To preve nt/counteract neutropenia that was assumed to represent the dose-limit ing toxicity, the hematopoietic growth factor GM-CSF was routinely adm instered. The objective of our trial was to determine the antitumor ef ficacy and tolerance of this combination regimen in patients with adva nced NSCLC. Patients and Methods: Forty consecutive patients with nonr esectable, measurable NSCLC (stage IIIB, 7; stage IV, 33) were treated with an intravenous combination chemotherapy regimen consisting of mi tomycin C 8 mg/m(2) on day 1, vinorelbine 40 mg/m(2) on days 1 and 21, and carboplatin 250 mg/m(2) on days 1 and 21: GM-CSF 5 mu g/kg was ad ministered subcutaneously on days 2-8 and 22-28. Treatment cycles were repeated every 6 weeks. All patients are evaluable in terms of toxici ty and response assessment. A total of 123 courses was administered. R esults: Objective tumor response was notes in 16 patients (40%; 95% co nfidence interval 23.9-56.7%), including 3 (7.5%) complete and 13 part ial responses. There was no change in 12 (31.5%) patients, and 12 had progressive disease. Median duration of response was 6 (range 3-15) mo nths, the median time to progression for all patients was 6.2 (range 1 -17.5) months, and the projected median survival time was 8.7 (range 1 -23.3) months; the I-year survival rate was 27.5%. Myelosuppression wa s the most frequently encountered adverse reaction; WHO grade 3 or 4 g ranulocytopenia and/or thrombocytopenia occurred in 42.5 and 12.5%, re spectively. Other toxicities were generally mild to moderate, and alwa ys fully reversible. Conclusion: With a 40% major response rate and di sease stabilization in one additional third of our patients, this drug combination seems to have significant activity against advanced metas tatic NSCLC. Due to its subjective tolerance and ease of administratio n, further investigation of this regimen in the palliative-intent care setting seems warranted.