A phase II trial of zoledronic acid in combination with cisplatin and docetaxel in non-small cell lung cancer patients with bone metastases.

Abstract

e18104 Background: Recent studies suggest that zoledronic acid (ZOL) may act by directly affecting tumor progression, possibly in synergy with chemotherapy. However, combination of ZOL and cisplatin may have the potential for deterioration in renal function. This study was conducted to evaluate the safety and efficacy of combined ZOL, cisplatin and docetaxel in patients with non- small cell lung cancer (NSCLC) with bone metastases. Methods: Cisplatin 80 mg/m2 and docetaxel 60 mg/m2 (CD) with ZOL 4mg were given intravenously on day 1 every 3-4 weeks for up to 4cycles. Main eligibility criteria included advanced NSCLC with bone metastases, no prior chemotherapy, and performance status of 0 or 1. The primary endpoint was feasibility defined by the number of patients receiving two cycles or more of CD with ZOL without severe toxicity. Data was also assessed prospectively on development of skeletal-related events (SRE), pain score, and urinary N-telopeptide (NTX) and bone-specific alkaline phosphatase as bone marker. Results: Between July 2007 and November 2009, 35 patients were enrolled in the study. The primary endpoint was met: Two or more cycles of CD with ZOL were administered in 29 (83%) patients. Within the first cycle, only 2 patients had an increase in serum creatinine levels of > 0.5 mg/dL from a baseline level. No grade 3 or 4 renal toxicity including serum creatinine increase was observed. To date, 7 PR, 16 SD, and 7 PD were observed among the 30 patients assessed for efficacy. After 6 weeks, the majority of patients experienced improvement in pain score and decrease of NTX level from baseline. Conclusions: Combination of CD with ZOL is well tolerated with acceptable renal toxicity as treatment of advanced NSCLC patients with bone metastases. No significant financial relationships to disclose.