Zoledronic acid (ZA) and treatment of bone metastasis in patients with advanced lung cancer (NSCLC and SCLC).

Background: The 7% of patients with lung cancer presents bone metastasis at the diagnosis and 30-40% of them develops during disease. In patients with NSCLC, ZA has significantly extended the time to first Skelethal-Related-Event (SRE), 2 months compared with placebo and it reduced at 27% the risk of skelethal events. Patients and methods: From January 2007 to January 2008, 24 patients with metastatic lung cancer, 18 NSCLC and 8 SCLC with ECOG-PS 0-2, previously treated with ZA every 4 weeks. Efficacy of ZA was assessed to postpone the first SRE, to reduce serum and urinary levels of bone tournover markers (serum Ca, Ca++, P, Mg and BALP; urinary Ca, P, CTX), to reduce pain (Brief Pain Inventory) and to improve QoL (EORTC QLQ-C30 questionnaire). Results: Bone tournover markers decreased during treatment with ZA. Serum and urinary P and ionized-Ca showed lower and longer time of reduction; serum and urinary Ca, BALP and CTX presented rapid reduction at the first administration of ZA. At bone metastasis or lung disease progression, markers presented a new increase not controlled by ZA. CTX was the most sensible and specific marker. Our data confirmed the efficacy of ZA in preventing SRE but also in delaying time to first SRE. During the observation period no SRE were observed. Patients with severe pain (range 7-10) at T0-time had a remarkable decrease in pain intensity, while patients starting with a low grade pain (range 2-6) had a greater flare- up after the first dose of ZA. At disease progression ZA had less efficacy on pain relief. QoL evaluation showed a remarkable worsening of several functions and a stability of the emotional one. Conclusions: ZA is effective in bone metastatic disease secondary to lung cancer. It reduces risk of SRE and prolongs time to the first event. Bone turnover markers decrease after the first administration. QoL improvement is directly related to pain relief while the progression of disease worsens QoL.