Zoledronate (bisphosphonate)

A prospective randomized trial of 1,970 patients compared IV zoledronate with oral clodronate in newly diagnosed patients receiving induction chemotherapy with or without consolidation.[147]

A prospective randomized trial of 1,970 patients compared IV zoledronate with oral clodronate in newly diagnosed patients receiving induction chemotherapy with or without consolidation.[147]

With a median follow-up of 3.7 years, zoledronate improved median OS from 44.5 months to 50.0 months (HR, 0.84; 95% CI, 0.74–0.96; P = .0118).[147][Level of evidence A1]

A prospective randomized trial of 1,970 patients compared IV zoledronate with oral clodronate in newly diagnosed patients receiving induction chemotherapy with or without consolidation.[147]

In this trial, both bisphosphonates were continued until time of relapse. As expected, skeletal-related events were also reduced in the zoledronate group (27% vs. 35%; P = .004).[148,149]

The improvement of median OS with zoledronate was confirmed in a Cochrane network meta-analysis.[150][Level of evidence A2] This meta-analysis also showed that 6 to 15 patients need treatment with bisphosphonates to prevent one skeletal-related event.

A clinical trial of zoledronate given once a month compared with zoledronate given every 12 weeks showed noninferiority for the 12-week regimen in 1,822 patients with bone metastases from breast cancer, prostate cancer, or multiple myeloma.[151] However, this study included only 278 patients with myeloma, and evaluation of this subgroup was insufficiently powered to establish noninferiority for the 12-week regimen. Nonetheless, this trial is used as justification for implementing a 12-week schedule at the start of therapy or as soon as maximal response has been reached.

Bisphosphonates are associated with infrequent long-term complications (in 3%–5% of patients), including osteonecrosis of the jaw and avascular necrosis of the hip.[152,153] For more information about osteonecrosis of the jaw, see Oral Complications of Cancer Therapies. These side effects must be balanced against the potential benefits of bisphosphonates when bone metastases are evident.[154] Bisphosphonates are usually given IV on a monthly basis for 2 years and then extended at the same schedule or at a reduced schedule (i.e., once every 3–4 months), if there is evidence of active myeloma bone disease.[155,156] On the aforementioned randomized trial,[148] which showed OS advantage, patients received bisphosphonates monthly until time of relapse.