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The Zoledronate versus ibandronate comparative evaluation (ZICE) trial compared two bisphosphonate treatments for breast cancer that has spread to the bones.


ZICE was a randomised, pragmatic, phase III, open-label, multi-centre, parallel group clinical trial to evaluate and compare the efficacy, safety profile, tolerability and patient satisfaction of daily oral ibandronate 50mg versus intravenous zoledronate 4mg as 3-4 weekly infusions in the treatment of breast cancer participants with bone metastases.

Study aim

This trial looked at two bisphosphonate treatments, zoledronate or ibandronate, for breast cancer that has spread to the bones. This trial compared zoledronate, given through a drip, with ibandronate tablets. These drugs treat bone weakness and bone pain caused by metastatic breast cancer. This trial was supported by Cancer Research UK.

When cancer spreads to the bone, it can make the bone weaker and more prone to damage and fractures. It can also be painful. Drugs called bisphosphonates can help to slow down damage to the bones and reduce pain. Zoledronate (Zometa) and ibandronate (Bondronat) are both bisphosphonates.

The overall aim of this trial was to see if ibandronate tablets are as good as zoledronate for breast cancer that has spread to the bone.

Skeletal related events

The research team looked at skeletal related events to see how well the treatments worked. Skeletal related events included:

  • fractures
  • radiotherapy for pain relief
  • spinal cord compression
  • orthopaedic surgery
  • high levels of calcium in the blood.


1,404 patients were randomly assigned to receive oral ibandronate (705 patients) or to receive i.v. zoledronate (699 patients). The main analysis included 654 patients in the ibandronate group and 672 in the zoledronate group. Annual rates of skeletal-related events were 0·5 per year with ibandronate and 0·44 per year with zoledronate.

The rate of skeletal-related events was therefore slightly higher in the ibandronate group. However, more patients in the zoledronic acid group had side effects relating to their kidneys than in the ibandronate group (32% vs 24%) but rates of osteonecrosis of the jaw (a serious side effect of bisphosphonates) were low in both groups (1% vs <1%). The most common grade 3 or 4 adverse events were fatigue, increased bone pain, joint pain, infection, and nausea or vomiting.

The results suggested that zoledronate is preferable to ibandronate in preventing skeletal-related events caused by bone metastases (non-inferiority was not shown). However, both drugs have acceptable side-effect profiles and the oral formulation is more convenient, and could still be considered if the patient has a strong preference or if difficulties occur with intravenous infusions.

Key facts

Start date 1 Sep 2005
End date 30 Sep 2010
Grant value £577,786
  • Published

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