Randomized phase II trial of adjuvant chemotherapy with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: TORG 0503.

OBJECTIVE: Adjuvant chemotherapy is standard of care for patients with completely resected stage IB, II and IIIA NSCLC. However, optimum chemotherapy regimen has not been determined. TORG0503 was undertaken to select a preferred platinum-based 3rd generation regimen in this clinical setting. MATERIALS AND METHODS: Patients with completely resected stage IB, IIA, IIB or stage IIIA NSCLC were stratified by stage (IB/IIA vs. IIB/IIIA) and institutions, and randomized to receive 3 cycles of docetaxel (60 mg/m2) plus cisplatin (80 mg/m2) (arm A) or paclitaxel (200 mg/m2) plus carboplatin (AUC 6) (arm B) on day 1, every 3 weeks. The primary endpoint of the study was 2-year relapse free survival, and the key secondary endpoints included overall survival, feasibility and toxicity. RESULTS: 111 patients were randomized, 58 patients to arm A and 53 to arm B. Patient demographics were balanced between the two arms. 93 % (54/58) of patients on the arm A and 92 % (49/53) patients on the arm B completed the planned 3 cycles of chemotherapy. There was no treatment-related death in both arms. The 2 and 5 year relapse free survival was 74.5 % (95 %CI: 68.6-80.4) and 61.6 % in the arm A, and 72.0 % (95 %CI: 65.7-78.3) and 46.0 % in the arm B. The overall 2, 5-year survival was 89.7 %, 73.9 % in the arm A and 86.9 %, 67.5 % in the arm B. CONCLUSION: Both docetaxel plus cisplatin and paclitaxel plus carboplatin are safe and feasible regimens as adjuvant chemotherapy. We choose docetaxel plus cisplatin as the control regimen for the next clinical trial.

A prospective cohort study of patients with non-squamous non-small cell lung cancer treated with bevacizumab.

First-line chemotherapy regimens that include bevacizumab (Bev) have been hypothesized to improve outcomes in patients with advanced non-squamous non-small cell lung cancer (non-sq NSCLC). Although approved to treat NSCLC in 2009, insufficient data exist on the clinical uses of Bev in Japan. The present study prospectively evaluated the efficacy and safety of Bev-containing combination chemotherapy. Eligible patients exhibited histologically or cytologically documented advanced or recurrent non-sq NSCLC. Patients were administered 15 mg/kg Bev with standard chemotherapy followed by maintenance Bev. The primary endpoints were progression-free survival (PFS) and safety. A total of 102 patients with non-sq NSCLC were enrolled, 44.1% of whose tumor carried epidermal growth factor receptor (EGFR) mutations. The overall response rate to the intervention was 44.1%, and the median PFS was 8.3 months [95% confidence interval (CI)=6.4-10.2 months]. The median overall survival was 26.3 months (95% CI=22.2-30.4 months). The incidence of Bev-associated severe adverse events was similar to those in previous trials, excluding a grade 3-4 hypertension rate of 30.4% in the present study. Multivariate analysis revealed that a higher TNM classification of malignant tumor staging-T factor, adjusted hazard ratio (HR)=1.33 (95% CI=1.10-1.61), and poor performance status [adjusted HR=1.63 (1.02-2.60)] were associated with significantly shorter PFS, whilst the EGFR exon 19 deletion was significantly associated with prolonged PFS [adjusted HR=0.47 (0.25-0.87)]. Bev-containing chemotherapy was safe and effective for patients with non-sq NSCLC in clinical settings in Japan. The EGFR exon 19 deletion was suggested as a positive predictive factor for the efficacy of Bev-containing chemotherapy.

[Results of questionnaire on decision-making to treat advanced non-small cell lung cancer based on American and European practical guidelines].

During 2009, practical routine guidelines for advanced non-small cell lung cancer used in Europe or USA were updated because the clinical benefits of molecular target agents were confirmed through several pivotal clinical trials. These molecular target agents appeared in guidelines which became available in Japan by the end of 2009. We made a questionnaire for decision-making to treat advanced non-small cell lung cancer based on these practical guidelines. Oncologists of lung cancer working in the Shinjuku area of Tokyo in Japan were eligible. Between March 15th and April 9th in 2010, 28 oncologists from 12 departments in 7 hospitals completed this questionnaire. Most of them made the global standard decision-making according to the new guidelines, including new proposals such as usage of epidermal growth factor receptor-tyrosine kinase inhibitors. There were 3 differences from the guidelines. 1)Platinum doublets were selected even in 2nd- or 3rd-line treatment because of the expected tumor shrinkage. 2)Single cytotoxic agents were selected even for 3rd-line treatment. The tendency of a backward shift in decision-making was observed. 3)There were few selections of regimens including bevacizumab because of medical systems such as DPC(Diagnosis Procedure Combination)that is Japanese DRG(Diagnosis-Related Group)/PPS(Prospective Payment System).