A PROSPECTIVE, CONTROLLED, NONRANDOMIZED STUDY ON PROPHYLACTIC PARENTERAL DICHLOROMETHYLENE BISPHOSPHONATE (CLODRONATE) IN MULTIPLE-MYELOMA

Bone resorption by osteoclasts causes neoplastic bone disease, which i s a significant cause of death in multiple myeloma (MM). Counteracting bone resorption with prophylactic bisphosphonates has delayed bane di sease, and this is expected to improve survival. Between January, 1987 and March, 1990, 341 evaluable previously untreated, consecutive pati ents with MM entered a prospective, multicenter study in which cytosta tic therapy was randomized. The first 148 patients recruited were not planned for prophylaxis and the following 193 were scheduled to receiv e parenteral, prophylactic clodronate. Clodronate was administered at a dose of 600-1000 mg/4-6 weeks and was started at diagnosis and conti nued throughout survival time. Data on clodronate prophylaxis were eva luated on both an intention-to-treat and a compliance analysis basis. The rate of response and the duration of response were independent of clodronate prophylaxis. Progression of skeletal disease occurred less often in patients who received the drug than in those who were not giv en prophylaxis (50.5 vs 34.8%; p<.02 by compliance analysis). Survival was longer for patients on clodronate prophylaxis than for those who were not planned for (p<.02 by intention to-treat-analysis) or for tho se who did not receive clodronate prophylaxis (p<.009 by compliance an alysis). Local pain associated with i.m. administration was the only s ignificant side effect of clodronate. Parenteral clodronate prophylaxi s prolongs survival in MM, probably because it allows better control o f bone disease and reduces deaths related to it.