RANDOMIZED PHASE-II TRIAL COMPARING DIFFERENT DOSES OF THE BISPHOSPHONATE IBANDRONATE IN THE TREATMENT OF HYPERCALCEMIA OF MALIGNANCY

Purpose: To evaluate the hypocalcemic effect and safety of three diffe rent doses of the bisphosphonate ibandronate in tumor-associated hyper calcemia, and to identify factors predicting response. Patients and Me thods: One hundred seventy-four cancer patients with a serum calcium l evel greater than 2.7 mmol/L (10.8 mg/dL) were enrolled onto the trial , If hypercalcemia persisted after fluid repletion, patients were rand omly assigned to treatment with 0.6 mg, 1.1 mg, and 2.0 mg of ibandron ate. Response, defined as restoration of normocalcemia, was evaluated by an intent-to-treat analysis. Results: One hundred seventy-three (99 %) patients were assessable for toxicity and 151 (87%) for efficacy, T he administration of 0.6 mg (group A), 1.1 mg (group B), or 2.0 mg (gr oup C) of ibandronate led to response rates of 44%, 52%, and 67%, resp ectively, Significantly more patients in group C responded than in gro up A (P = .0276). Of the various parameters examined, only the initial serum calcium level (P < .0001; odds ratio, 0.083) and the dose of ib andronate (P = .0162; odds ratio, 2.094) correlated with response. One hundred ninety five adverse events (AEs) were reported, 99 classified as serious and 96 as nonserious. Three serious and sixteen nonserious AEs were considered related to ibandronate treatment. The three serio us AEs were one case with thrombocytopenia, one with nausea, and one w ith fever. Conclusion: Ibandronate therapy led to a dose-dependent red uction in serum calcium levels. The response to ibandronate treatment correlated negatively with the initial serum calcium level and positiv ely with the dose administered. A dose of 2 mg was necessary to achiev e a response rate comparable to that in previous studies with the biph osphonates pamidronate and clodronate. Because the incidence of drug a ssociated AEs was low, a dose escalation of ibandronate can be recomme nded for further clinical trials. (C) 1996 by American Society of Clin ical Oncology.