Background: Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.gov id.:.NCT00345059).
Methods: NSCLC patients, aged <75, PS 0-2, who had failed platinum-based chemotherapy, were randomly assigned with a 3:1:1 ratio to: arm A, weekly docetaxel (33.3mg/m(2) on days 1, 8, 15 q 4 weeks); arm B, weekly docetaxel (30 mg/m(2) on days 1, 8, 15) plus gemcitabine (800 mg/m(2) on days 1, 8 q 4 weeks) or plus vinorelbine (20mg/m(2) on days 1, 8 q 4 weeks) depending on which of the two had been used in first line; arm C, weekly docetaxel (as in arm B) plus capecitabine (625 mg/m(2) twice daily on days 5-18 q 4 weeks). Primary end-point was overall survival (OS). Two comparisons were planned: arm B vs. A and arm C vs. A. Overall, 375 patients had to be randomized. Response was assessed by RECIST, quality of life (QoL) by EORTC questionnaires.
Results: 84 patients were randomized from May 2005 to December 2006, when the trial was prematurely stopped due to the slow accrual. After 62 deaths, median OS was 40.0 weeks in arm A, 32.6 weeks in arm B (p=0.18 vs. A) and 39.7 weeks in arm C (p=0.90 vs. A). Response rate was 6.4, 16.7 and 5.3%, and median progression-free survival was 12.4, 13.1 and 11.9 weeks, for arms A, B and C, respectively. Patients in arm B had significantly more grade 3-4 haematological and non-haematological toxicity compared to arm A, and patients in arm C had significantly more grade 3-4 non-haematological toxicity compared to arm A. No relevant differences were found in QoL analysis, with the exception of significant worsening in appetite, vomiting and hemoptysis for patients in arm B.
Conclusion: Due to early termination, the trial does not have the planned statistical power. However, available data do not support the role of docetaxel-based combination chemotherapy as second line in advanced NSCLC.