The aim of this open-label, multicenter, randomized phase II trial was to evaluate the efficacy and safety of zoledronic acid, nitrogen-containing bisphosphonate, in combination with docetaxel in previously treated NSCLC patients with bone metastases.Material and methods
Previously treated NSCLC patients with bone metastases were randomly assigned to receive either docetaxel 60 mg/m2 with or without zoledronic acid 4 mg on day 1 every 21 days. The study treatment was repeated until disease progression, or intolerable toxicity. The primary end point was progression-free survival (PFS), and secondary end points were overall survival (OS), objective response rate (ORR), skeletal-related event (SRE) rate, SRE-free survival, and safety. All patients were followed-up for 1 year after the last patient enrollment.Results
From May 2007 to March 2010, 100 patients were enrolled from 15 institutions; 50 patients were randomly assigned to docetaxel plus zoledronic acid (DZ) and 50 to docetaxel alone (D). Patient characteristics were well balanced between the two arms. Forty-nine patients in the DZ group received zoledronic acid with a median of three cycles (range 1–19). Of 94 patients for efficacy analysis (48 for DZ and 46 for D), the median OS was 10.4 (95% CI, 7.0–15.8) months in the DZ group, when compared with 9.7 (95% CI, 6.1–12.5) months in the D group (stratified log-rank test, P = 0.62). The median PFS were 2.7 and 2.6 months in DZ and D, respectively (stratified log-rank test, P = 0.89), with corresponding ORRs of 8% (95% CI, 2–20) and 4% (95% CI, 1–14). The median SRE-free survival in the two groups was 7.2 and 6.0 months, respectively (stratified log-rank test, P = 0.84). The SRE rates at 1 year were 30% (95% CI, 18–48) for the DZ group and 39% (95% CI, 24–57) for the D group. There were no clinically relevant differences in the frequencies of grade 3–4 adverse events between the two groups. No treatment-related death was observed in the DZ group.Conclusions
The addition of zoledronic acid to docetaxel was well tolerated, but did not improve PFS and OS in NSCLC patients with bone metastases.