title: Not too little, not too much-just right! (Better ways to give high dose melphalan).
abstract: Of the 13 286 autologous haematopoietic cell transplant procedures reported in the US in 2010-2012 for plasma cell disorders, 10 557 used single agent, high-dose melphalan. Despite 30 years of clinical and pharmacokinetic (PK) experience with high-dose melphalan, and its continuing central role as cytoreductive therapy for large numbers of patients with myeloma, the pharmacodynamics and pharmacogenomics of melphalan are still in their infancy. The addition of protectant agents such as amifostine and palifermin allows dose escalation to 280 mg/m(2), but at these doses it is cardiac, rather than gut, toxicity that is dose-limiting. Although combination with additional alkylating agents is feasible, the additional TRM may not be justified when so many post-consolidation therapies are available for myeloma patients. Current research should optimise the delivery of this single-agent chemotherapy. This includes the use of newer formulations and real-time PKs. These strategies may allow a safe and effective platform for adding synergistic novel therapies and provide a window of lymphodepletion for the addition of immunotherapies.
authors.affiliation: 1] Departments of Oncology The Children's Hospital at Westmead, Westmead, New South Wales, Australia [2] The Department of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Shaw
authors.affiliation: 1] Departments of Oncology The Children's Hospital at Westmead, Westmead, New South Wales, Australia [2] Biochemistry The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
authors.forename: C E
authors.initials: CE
authors.lastname: Nath
authors.affiliation: Department of Medicine, Division of Haematology-Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Cleveland, OH, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Lazarus
mesh_terms: D004999:Amifostine / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008558:Melphalan / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009101:Multiple Myeloma / Q000628:therapy; D009369:Neoplasms / Q000628:therapy*; D009765:Obesity / Q000150:complications; D015203:Reproducibility of Results
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D051523:Fibroblast Growth Factor 7; D004999:Amifostine; D008558:Melphalan