Recurrent Intracranial Ewing Sarcoma.

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Abstract

19. J Clin Oncol. 1995 Jul;13(7):1786-99. doi: 10.1200/JCO.1995.13.7.1786. High-dose intravenous melphalan: a review. Samuels BL(1), Bitran JD. Author information: (1)Department of Medicine, Lutheran General Hospital, University of Chicago School of Medicine, Park Ridge, IL, USA. PURPOSE: To review the clinical pharmacology and clinical trials that have used intravenous (IV) high-dose melphalan (HDM). METHODS: We reviewed the mechanism of action, clinical pharmacology, and clinical studies of HDM with and without autologous bone marrow support (ABMT) or peripheral-blood progenitor cells (PBPCs) in the following disease areas: myeloma, ovarian cancer, malignant lymphoma, breast cancer, neuroblastoma, Ewing's sarcoma, and acute leukemia. RESULTS: HDM has a distribution half-life (t1/2 alpha) of 5 to 15 minutes and an elimination half-life (t1/2 beta) of 17 to 75 minutes at doses of 140 to 180 mg/m2, with significant intrapatient variability. At these doses, a wide range of areas under the concentration/time curve (AUC) have been reported, ie, 146 to 1,515 mg/min/mL. HDM has significant clinical activity in patients with multiple myeloma in relapse or when used as consolidative therapy in relapsed ovarian cancer, relapsed Hodgkin's disease, breast cancer, and relapsed neuroblastoma. Additional studies are required to determine the activity of HDM in Ewing's sarcoma or acute leukemia. Toxicities of HDM include myelosuppression, moderate nausea and vomiting, moderate to severe mucositis and diarrhea, and, infrequently, hepatic venoocclusive disease. CONCLUSION: HDM has become an established and effective salvage regimen for children with relapsed neuroblastoma, as well as an effective consolidative treatment for children with high-risk disease (stage IV). HDM is emerging as an active and effective mode of treatment in patients with stage II and III myeloma. The favorable toxicity profile of HDM and the availability of PBPCs allows for repetitive therapy. DOI: 10.1200/JCO.1995.13.7.1786