title: Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation.
abstract: Autologous stem cell transplantation (SCT) with high-dose melphalan (HDM, 200 mg/m2) is the most effective therapy for multiple myeloma. To determine the feasibility of combining carmustine (300 mg/m2) with HDM, we enrolled 49 patients with previously treated Durie-Salmon stage II/III myeloma (32M/17W, median age 53) on a phase I/II trial involving escalating doses of melphalan (160, 180, 200 mg/m2). The median beta2-microglobulin was 2.5 (0-9.3); marrow karyotypes were normal in 88%. The phase I dose-limiting toxicity was > or =grade 2 pulmonary toxicity 2 months post-SCT. Other endpoints were response rate and progression-free survival (PFS). HDM was safely escalated to 200 mg/m2; treatment-related mortality was 2% and > or =grade 2 pulmonary toxicity 10%. The complete (CR) and near complete (nCR) response rate was 49%. With a median post-SCT follow-up of 2.9 years, the PFS and overall survival (OS) post-SCT were 2.3 and 4.7 years. PFS for those with CR or nCR was 3.1 years while for those with stable disease (SD) it was 1.3 years (P=0.06). We conclude that carmustine can be combined with HDM for myeloma with minimal pulmonary toxicity and a high response rate.
authors.affiliation: Hematology Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. comenzor@mskcc.org
authors.forename: R L
authors.initials: RL
authors.lastname: Comenzo
authors.forename: H
authors.initials: H
authors.lastname: Hassoun
authors.forename: T
authors.initials: T
authors.lastname: Kewalramani
authors.forename: V
authors.initials: V
authors.lastname: Klimek
authors.forename: M
authors.initials: M
authors.lastname: Dhodapkar
authors.forename: L
authors.initials: L
authors.lastname: Reich
authors.forename: J
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: M
authors.initials: M
authors.lastname: Fleisher
authors.forename: D
authors.initials: D
authors.lastname: Filippa
authors.forename: S D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan; D002330:Carmustine