Randomized Study of Adjuvant Chemotherapy for Completely Resected Stage I, II, or IIIA Non–Small-Cell Lung Cancer

• Published in: JNCI : Journal of the National Cancer Institute 2003-10, Vol.95 (19), p.1453-1461
• Main Authors: Scagliotti, Giorgio V., Fossati, Roldano, Torri, Valter, Crinò, Lucio, Giaccone, Giuseppe, Silvano, Giovanni, Martelli, Massimo, Clerici, Maurizia, Cognetti, Francesco, Tonato, Maurizio
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Chemotherapy; Chemotherapy, Adjuvant; Cisplatin - administration & dosage; Clinical outcomes; Clinical trials; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Italy; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Medical sciences; Middle Aged; Mitomycin - administration & dosage; Multivariate Analysis; Neoplasm Staging; Odds Ratio; Patient Compliance; Patient Selection; Pharmacology. Drug treatments; Proportional Hazards Models; Prospective Studies; Survival Analysis; Treatment Outcome; Vindesine - administration & dosage
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djg059

Background: Surgery is the primary treatment for patients with stage I, II, or IIIA non–small-cell lung cancer (NSCLC). However, long-term survival of NSCLC patients after surgery alone is largely unsatisfactory, and the role of adjuvant chemotherapy in patient survival has not yet been established. Methods: Between January 1994 and January 1999, 1209 patients with stage I, II, or IIIA NSCLC were randomly assigned to receive mitomycin C (8 mg/m2 on day 1), vindesine (3 mg/m2 on days 1 and 8), and cisplatin (100 mg/m2 on day 1) every 3 weeks for three cycles (MVP group; n = 606) or no treatment (control group; n = 603) after complete resection. Randomization was stratified by investigational center, tumor size, lymph-node involvement, and the intention to perform radiotherapy. The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment. Survival curves were analyzed using the log-rank test. All statistical tests were two-sided. Results: After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in overall survival (hazard ratio = 0.96, 95% confidence interval = 0.81 to 1.13; P = .589) or progression-free survival (hazard ratio = 0.89, 95% confidence interval = 0.76 to 1.03; P = .128). Only 69% of patients received the three planned cycles of MVP. Grades 3 and 4 neutropenia occurred in 16% and 12%, respectively, of patients in the MVP arm. Radiotherapy was completed by 65% of patients in the MVP arm and by 82% of patients in the control group. In the multivariable analysis, only disease stage and sex were associated with survival. Conclusion: This randomized trial failed to prospectively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC. Given the poor compliance with the MVP regimen used in this study, future studies should explore more effective treatments.