ORLANDODaily doses of
oral ibandronate (investigational, Hoffmann-La Roche, Basel, Switzerland), a
highly potent third-generation bisphosphonate, significantly reduced the
incidence of new skeletal complications in breast cancer patients with
metastatic bone disease enrolled in a phase III trial. The mean number of new
events per patient was 1.36 for women taking oral ibandronate at 20
mg/d and 1.43 at 50 mg/d, compared with 2.23 for women taking placebo.
The results were discussed at the American Society of
Clinical Oncology 38th Annual Meeting (abstract 176) by the study’s lead
investigator, Debu Tripathy, MD, of The University of Texas Southwestern
Medical Center, Dallas.
Although the 20-mg and 50-mg doses of oral ibandronate
produced similar results, the higher dose was more effective in reducing bone
turnover and painful lesions requiring radiotherapy. According to the
researchers, these results "indicate that ibandronate 50 mg/d is the most
appropriate clinical dose."
Bisphosphonates inhibit osteoclast-mediated bone resorption
and are increasingly being used to manage metastatic bone disease as an
alternative to radiation and systemic palliative therapies that are associated
with significant side effects. Although bisphosphonates for metastatic bone
disease are usually delivered intravenously, the researchers postulated that "a
simple oral treatment could enhance tolerability and convenience without
The 435 women in the study all had advanced breast cancer
with confirmed metastases and adequate performance status. More than 69% of
patients in all three arms had been treated with hormonal therapy and more than
63% had received chemotherapy. Patients were randomized to placebo (n = 143) or
oral ibandronate at 20 mg/d (n = 144) or 50 mg/d (n = 148) for up to 96 weeks.
Compared with placebo, both iban-dronate arms had a
significant reduction in the mean rates of skeletal events per patient yearfor
the ibandronate arms, the mean rates were 0.97 at 20 mg/d and 0.98 at 50 mg/d,
compared with 1.20 for the placebo group (see Table 1). A reduction was seen
for each event and reached statistical significance for painful lesions
requiring radiotherapyfor the ibandro-nate arms, the mean rates were 0.81 at
20 mg/d and 0.77 at 50 mg/d, compared with 0.99 for the placebo group.
Benefits were also seen in secondary endpoints, including a
rapid reduction in bone pain and a significant reduction in analgesic
requirements (Table 2). Ibandronate, both arms combined, produced a
significant, treatment-related sustained reduction in biochemical markers of
bone turnover, compared with placebo (P = .0001) and a significant
benefit was seen in the 50-mg group, compared with the 20-mg group (P =