HIGH-DOSE INTRAVENOUS MELPHALAN - A REVIEW

Purpose: To review the clinical pharmacology and clinical trials that have used intravenous (IV) high-dose melphalan (HDM). Methods: We revi ewed the mechanism of action, clinical pharmacology, and clinical stud ies of HDM with and without autologous bone marrow support (ABMT) or p eripheral-blood progenitor cells (PBPCs) in the following disease area s: myeloma, ovarian cancer, malignant lymphoma, breast cancer, neurobl astoma, Ewing's sarcoma, and acute leukemia. Results: HDM has a distri bution half-life (t(1/2)alpha) of 5 to 15 minutes and an elimination h alf-life (t(1/2)beta) of 17 to 75 minutes at doses of 140 to 180 mg/m( 2), with significant intrapatient variability, At these doses, a wide range of areas under the concentration/time curve (AUG) have been repo rted, ie, 146 to 1,515 mg/min/mL. HDM has significant clinical activit y in patients with multiple myeloma in relapse or when used os consoli dative therapy in relapsed ovarian cancer, relapsed Hodgkin's disease, breast cancer, and relapsed neuroblastoma, Additional studies are req uired to determine the activity of HDM in Ewing's sarcoma or acute leu kemia, Toxicities of HDM include myelosuppression, moderate nausea and vomiting, moderate to severe mucositis and diarrhea, and, infrequentl y, hepatic venoocclusive disease, Conclusion: HDM has become an establ ished and effective salvage regimen for children with relapsed neurobl astoma, as well as an effective consolidative treatment for children w ith high-risk disease (stage IV). HDM is emerging as an active and eff ective made of treatment in patients with stage II and III myeloma. Th e favorable toxicity profile of HDM and the availability of pBPCs allo ws for repetitive therapy,