Long‐term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors

Abstract

BACKGROUNDThe authors previously reported the efficacy of a dose of 4 mg of zoledronic acid in reducing skeletal complications in patients with bone metastases secondary to lung carcinoma and other solid tumors (except carcinomas of the breast and prostate). In the current study, they update these results and report the long‐term efficacy and safety of 21 months of treatment with zoledronic acid in a randomized, placebo‐controlled trial.METHODSA total of 773 patients were randomized to receive zoledronic acid (4 mg or 8 mg) or placebo via a 15‐minute infusion every 3 weeks for 21 months. The 8‐mg dose later was reduced to 4 mg (8/4‐mg group). The primary efficacy endpoint was the percentage of patients at 21 months with ≥ 1 skeletal‐related event (SRE) (pathologic fracture, spinal cord compression, radiation therapy to bone, or surgery to bone). Secondary analyses (time to first SRE, annual incidence of SREs, and multiple‐event analysis) included hypercalcemia of malignancy.RESULTSFewer patients treated with zoledronic acid developed at least 1 SRE at 21 months compared with patients treated with placebo (39% of those treated at the 4‐mg dose [P =0.127] and 36% of those treated at the 8/4‐mg dose [P = 0.023], compared with 46% of those treated with placebo). Furthermore, 4 mg of zoledronic acid significantly delayed the median time to first SRE (236 days with 4 mg vs. 155 days with placebo; P = 0.009) and significantly reduced the annual incidence of SREs (1.74 per year with the 4‐mg dose vs. 2.71 per year with placebo; P = 0.012). Moreover, the 4‐mg dose of zoledronic acid was found to reduce the risk of developing a skeletal event by 31% (hazard ratio of 0.693; P = 0.003). Zoledronic acid was found to be well tolerated with long‐term use; the most commonly reported adverse events in all treatment groups included bone pain and the transient, acute‐phase reactions of nausea, anemia, and emesis.CONCLUSIONSTo the authors' knowledge, zoledronic acid is the first bisphosphonate to demonstrate long‐term safety and efficacy in this patient population. Cancer 2004. © 2004 American Cancer Society.

Prognostic factors for skeletal complications from metastatic bone disease in breast cancer

“…At present, there is no such suitable data set. Alternatively, patients from the pamidronate arm of the Rosen trial [18,19,26] could be used, but this is less than optimal because risks and risk factors may be different in this group of patients, pamidronate is now used less often, and ZOL produced some significant SRE benefits beyond those produced by pamidronate [11,19]. A further challenge in validation of models for risk classification of SREs is the presence of the competing risk for death.…”

“…Thus, bisphosphonates are now standard therapy in patients with bone metastases from BC [6]. Particularly, the large, multicenter, randomized, placebo-controlled trials of zoledronic acid (ZOL) demonstrated reduction in the frequency of SREs versus placebo in BC patients [7], and also in patients with castration-resistant prostate cancer [8,9] and a broad range of other solid tumors, including lung cancer [10,11].…”

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

“…Despite this recent increase in treatment options, a significant proportion of patients will eventually develop symptoms of bone progression during the course of the disease [6]. In fact, overall, bone metastases and their skeletal-related events are not controlled in approximately 20-40% of cancer patients [7][8][9], and the current therapeutic regimens leave B45% of patients with inadequate or undermanaged pain control [10,11].…”

The benefits of timely intervention with zoledronic acid in patients with metastatic prostate cancer to bones: a retrospective study of the US Veterans Affairs population

“…19 A retrospective analysis of a phase III study suggested that ZA therapy may improve survival in a subgroup of lung cancer patients with high bone turnover when compared with placebo. 20,21 Another study showed better survival with ZA over clodronate in newly diagnosed multiple myeloma patients. 22 The present study retrospectively examined the outcomes of ZA treatment in a population of US veterans with bone-metastatic prostate cancer.…”