In 12 of 93 hypercalcemic patients with metastatic advanced
breast cancer treated with
tamoxifen the most common life-threatening metabolic complication of flare
hypercalcemia developed. All the hypercalcemic patients had osteolytic or mixed lytic and blastic bone
metastases. In patients with advanced
breast cancer,
hypercalcemia develops within the first few weeks of initiation of
tamoxifen therapy. In our study group,
calcium levels were measured frequently in both serum and urine samples by a semi-autoanalyzer and an autoanalyzer, using standard methods. Elevation of
calcium levels was noticed in the
tamoxifen-receiving hypercalcemic
breast cancer patients, and levels returned to normal when
tamoxifen was withdrawn. The median duration of flare
hypercalcemia was 9 days (range, 4-16 days). The median
calcium value was 13.6 mg/dl (range, 11.7-15.8). The diagnosis of
tamoxifen flare
hypercalcemia was based on the normal pretreatment serum or urine
calcium values and the occurrence of
hypercalcemia within the first few weeks of
tamoxifen initiation. There are no specific treatment recommendations for
hormone flare
hypercalcemia, except for
tamoxifen withdrawal, which is usually temporary, and the introduction of a low dose of an antihypercalcemic
drug. We evaluated the effect of such a
drug,
gallium nitrate, on flare
hypercalcemia. All the patients were treated with hydration, and 6 patients, whose
calcium level was above 13.6 mg/dl, were treated with a moderate dose of
gallium nitrate (200 mg/m(2) per kg) for 5 consecutive days, they achieved normocalcemia and continued with
tamoxifen. The median time from hormonal
drug initiation to flare
hypercalcemia was 17.5 days, and median duration was 9 days. The above result indicates that the serious metabolic complication of
hypercalcemia develops due to the iatrogenic effect of
tamoxifen, but it can be controlled with an antihypercalcemic
drug,
gallium nitrate, while continuing
tamoxifen therapy. It seems that the use of
gallium nitrate in the treatment of flare
hypercalcemia could allow safe readministration of
tamoxifen and prevent premature
tamoxifen discontinuance or withdrawal.