A prospective, open-label, randomized phase II trial to evaluate the changes of bone resorption marker after administration of zoledronic acid (ZOL) in nasopharyngeal cancer (NPC) patients with bone metastases (BM)

Abstract

6063 Background: ZOL is the only bisphosphonate that has demonstrated efficacy for the prevention of skeletal-related events (SREs) in patients with BM in a wide range of tumor types. Recent retrospective analyses also showed that normalization of N-telopeptide of type I collagen (NTX) over 3 months by the treatment of ZOL provided a continuum of SRE risk reduction and survival benefit in patients with BM (Lipton et al. ASCO 2007). Therefore, we conducted the prospective open-label randomized phase II trial to evaluate the changes of NTX after administration of ZOL in NPC patients with BM. Methods: Newly diagnosed NPC patients with BM were randomized to receive chemotherapy of cisplatin (20mg/m2 IV, D1–5) plus FU (500mg/m2 IV, D1–5) (CF regimen, q3wks) and intravenous ZOL (4mg, q4wks, for 3months, CF+ZOL Group) or the same chemotherapy alone (CF Group). Urinary NTX was measured by ELISA method (Coleman et al. JCO 2005) at baseline and 1, 2, 3 months after administration of ZOL in all patients. Results: Sixty patients were enrolled into the study, 30 patients in each group. The median chemotherapy cycles was the same (4 and 4, respectively) in two groups. The median baseline NTX level had no difference between the two groups (75.4 vs. 95.6 nM BCE/mM creatinine, respectively p>0.05). The NTX decreased 65.9% within 1 month in CF+ZOL group, whereas NTX increased 2.61 % in CF group (p<0.01). The median NTX decrease percentage in 2,3 months after treatment were 70.8%, 86.5% in CF+ZOL Group and 15.9%, 34.5% in CF Group respectively (p<0.01, p<0.01). Conclusions: ZOL administered with chemotherapy (CF) consistently reduced NTX levels in NPC patients with BM, indicating potential benefit of ZOL may exist in this group of patients. The value of NTX reduction in NPC patients with BM need to be further studied in larger prospective randomized trials. [Table: see text] [Table: see text]