Single-Dose Radiation Standard Remains for Bone Metastases

Zosia Chustecka

September 29, 2011

September 29, 2011 (Stockholm, Sweden) — The standard treatment of a single dose of radiation for bone metastases in men with prostate cancer provided relief similar to that seen after an intravenous dose of the bisphosphonate ibandronate (Boniva). These results come from the first phase 3 trial to compare the 2 approaches, and were presented here at the 2011 European Multidisciplinary Cancer Congress.

"We found that using ibandronate was as good as a single dose of radiotherapy in controlling pain," reported principal investigator Peter Hoskin, MD, consultant clinical oncologist at the Mount Vernon Cancer Center, Northwood, United Kingdom.

However, Daniel Zips, MD, from the Technical University, Dresden, Germany, who was a discussant for this paper, noted that there was a trend in favor of radiotherapy.

Because of this, Dr. Zips concludes that "a single dose of radiation should remain the standard of care for bone metastases."

Ibandronate represents an effective treatment option for special clinical situations, such as for patients in whom radiation is contraindicated, he added. "It also offers a treatment option for nonresponders to radiotherapy."

Dr. Hoskin concurred. "It is important to stress that radiotherapy still has a crucial role to play and is a highly effective treatment for many cancer patients. For patients with solitary metastases, pathological fracture (where the bone breaks due to weakness), and neurological complications of bone metastases, it remains the treatment of choice."

"Our research adds to the arsenal of many effective treatments now available, and we believe that the findings will be applicable to other primary cancers that can lead to bone metastases — for example, breast cancer, where they are very common," he concluded.

We need better treatments.

Ibandronate is currently marketed for osteoporosis, but is being studied for the treatment of bone metastases in cancer patients. Two other bisphosphonates are already approved for this use — pamidronate (Aredia) and zoledronic acid (Zometa) — as is the novel bone agent denosumab (Xgeva).

Dr. Zips emphasized that the trial found an overall response rate of only 50% for both approaches, which shows "that we need better treatments." Half of these patients with painful bone metastases gain no relief.

Slight Differences in Pain Relief

The trial was conducted in 470 patients with prostate cancer and painful bone metastases. They were randomized to receive either a single dose of radiation (8 Gy) or a single intravenous infusion of ibandronate (6 mg).

A combination of 2 measures of pain relief were used: the World Health Organization (WHO) pain ladder; and the Mercadante score, which measures analgesic use in morphine equivalents (an appositive difference from baseline indicates worsening pain relief).

At 4 weeks, the WHO response rate was 53% in the radiotherapy group, and 49% in the ibandronate group (P = .49), and the Mercadante score was –3.2 units in the radiotherapy group and +1.2 units in the ibandronate group (P = .11).

However, the proportion of patients with a high score difference at 4 weeks (≥5.86 units) was 10% for radiotherapy and 20% for ibandronate (P = .004), Dr. Hoskin noted.

At 6 months, the mean differences were +3.99 for radiotherapy and +1.95 for ibandronate (P = .66); at 12 months, there was no difference.

Patients who reported no benefit from therapy at 4 weeks were allowed to cross over into the other treatment group. In all, 24% of patients initially treated with radiotherapy switched to ibandronate, and 31% of those initially treated with ibandronate switched to radiotherapy (P = .10).

Median overall survival was 11.8 months for radiotherapy alone, 11.4 months for ibandronate alone, 12.7 months for radiotherapy followed by ibandronate, and 16.8 months for ibandronate followed by radiotherapy.

Dr. Hoskin noted that "although there were more patients in the ibandronate group with worse Mercadante scores who need retreatment at the 4-week assessment, by 6 and 12 months, there was no long-term difference in pain relief between the 2 groups." Dr. Zips said that the difference in pain scores at 4 weeks was not statistically significant, and neither was the difference in patients who crossed over to the other therapy, but both showed a "statistical trend" in favor of radiotherapy.

He also noted the increased survival time in the patients who were treated with ibandronate followed by radiotherapy, and wondered if there "might be an interaction between ibandronate and radiotherapy that could be exploited and could be beneficial."

More work is needed, and more efforts need to be directed at this complication of painful bone metastases in cancer patients, because this is a "big problem, with a strong negative impact on quality of life and maybe survival." "We need more research on this," he emphasized.

This trial was funded by Roche, the manufacturer of ibandronate, as well as by Cancer Research UK and the UK National Cancer Research Network.

2011 European Multidisciplinary Cancer Congress (EMCC): Abstract 7LBA. Presented September 25, 2011.