ZOMETA IN BREAST CANCER

In the randomized phase II trial, zoledronate appeared to limit dissemination of tumor cells to bone marrow, the investigators report.

The data released online today in The Lancet Oncology were first presented in preliminary form two years ago at a meeting of the American Society of Clinical Oncology (see Reuters Health eLine report, May 16, 2008).

Zoledronic acid is an osteoclast-inhibiting bisphosphonate. Two trials published last year showed a disease-free survival benefit from zoledronic acid treatment in women with early breast cancer receiving adjuvant endocrine therapy.

The current study included 120 women with stage II-III newly diagnosed breast cancer and no evidence of distant metastasis by CT or bone scan.

The authors, led by Dr. Rebecca Aft of Washington University School of Medicine, St. Louis, randomly assigned half the patients to receive intravenous zoledronate 4 mg every three weeks for one year. Starting at the same time, all patients received four cycles of neoadjuvant epirubicin plus docetaxel every three weeks with granulocyte-stimulating factor support.

At baseline, bone marrow from each anterior iliac crest showed disseminated tumor cells in 26 of 60 zoledronate-treated patients (43%) and 28 of 58 controls (48%). When bone marrow studies were repeated at 3 months (after 4 cycles of chemotherapy), these women did not have significant changes in detectable tumor cells.

But among the women with no detectable tumor cells in their bone marrow at baseline, 27 of 31 (87%) in the zoledronate group were still negative at 3 months, compared to 10 of 25 (40%) in the control group (p = 0.03).

The authors postulate that "chemotherapy leads to increased bone turnover and the release of growth factors, providing a favorable environment" for disseminated tumor cells, but "this effect is abrogated by treatment with bisphosphonates."

They caution, however, that their study was not designed for this comparison, and that false-negative bone marrow results cannot be excluded, so the findings should be confirmed in larger trials.

By 12 months, with only 79 women still evaluable, there was no difference between the groups in the proportion of patients with tumor cells in bone marrow.

The authors saw no significant differences in rates of pathological complete response or disease-free or overall survival at 12 and 24 months. Zoledronic acid did improve bone-mineral density at the hip and wrist at 12 months.

Rates of adverse events were similar in the two groups, although one woman treated with zoledronic acid developed osteonecrosis of the jaw.

The study was funded by Pfizer Inc. and Novartis Pharmaceuticals.

Lancet Oncol 2010.