A trial investigating the use of Zoledronic acid ( Zoledronate; Zometa ) to aid chemotherapy for breast cancer has not found a significant benefit for reducing the risk of recurrence.
Zometa should not be used routinely in treatment of the disease.
Zoledronic acid is one of the bisphosphonates, a group of drugs mainly used to treat osteoporosis. However they are also given to cancer patients to protect against the effects of secondary bone cancer, such as pain and weakness in the bones.
Laboratory studies have suggested that Zoledronic acid might also have direct anti-tumour effects and enhance other chemotherapy treatments, so the multi-centre AZURE trial was set up to investigate further.
Led by Robert Coleman at the Weston Park Hospital in Sheffield, UK, the trial recruited 3,360 patients with stage II/III breast cancer from 174 centres. They were randomised to receive chemotherapy and/or endocrine therapy, with or without Zoledronic acid.
An interim analysis of the trial's progress indicated that patients were seeing no clinical benefit from the treatment.
This confirmed the drug's lack of impact, apart from in a sub-set of women who had undergone menopause five or more years previously. Here, the overall survival rate was 85% compared to 79% for women who did not receive Zoledronic acid.
The effect was independent of the characteristics of the disease as shown by the stage of the tumour, oestrogen receptor status, and lymph node involvement.
At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group ( adjusted hazard ratio in the Zoledronic acid group, 0.98; P=0.79 ).
Disease recurrence or death occurred in 377 patients in the Zoledronic acid group and 375 of those in the control group. The numbers of deaths, 243 in the Zoledronic acid group and 276 in the control group, were also similar, resulting in rates of overall survival of 85.4% in the Zoledronic acid group and 83.1% in the control group ( adjusted hazard ratio, 0.85; P=0.07 ).
In the Zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw ( cumulative incidence, 1.1%; P