DOSE-RESPONSE STUDY OF IBANDRONATE IN THE TREATMENT OF CANCER-ASSOCIATED HYPERCALCEMIA

Hypercalcaemia is an important cause of morbidity in malignant disease . We studied the efficacy and safety of intravenous ibandronate (a new , potent bisphosphonate) in a multicentre study of 147 patients with s evere cancer-associated hypercalcaemia which had been resistant to tre atment with rehydration alone. Of 131 randomized patients who were eli gible for evaluation, 45 were allocated to receive 2 mg ibandronate, 4 4 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calc ium values fell progressively in each group from day 2, reaching a nad ir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effe ctive than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mM afte r treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a log istic regression analysis, three factors were found to predict respons e; ibandronate dose (higher doses were more effective), severity of pr esenting hypercalcaemia (severe hypercalcaemia was associated with les s complete response) and tumour type (patients with breast carcinoma a nd haematological tumours responded better than those with other tumou rs). Ibandronate was generally well tolerated and no serious drug-rela ted adverse events were observed. We conclude that ibandronate is a sa fe, well tolerated and effective treatment for cancer-associated hyper calcaemia, which should prove a useful addition to the current range o f therapies available to treat this condition.