title: A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto-SCT.
abstract: We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (⩾nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, ⩾nCR 22 vs 39%, P=0.03, ⩾PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR)=1.15 (95% confidence interval (CI), 0.62-2.13, P=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52-1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen-related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington, Seattle, WA, USA.
authors.forename: W I
authors.initials: WI
authors.lastname: Bensinger
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Becker
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington, Seattle, WA, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Gooley
authors.affiliation: University of Washington, Seattle, WA, USA.|VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Chauncey
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington, Seattle, WA, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington, Seattle, WA, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Gopal
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington, Seattle, WA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington, Seattle, WA, USA.
authors.forename: O W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lill
authors.affiliation: James P Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Ifthikharuddin
authors.affiliation: Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Vescio
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|University of Washington, Seattle, WA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Holmberg
authors.affiliation: Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000368:Aged; D064592:Autografts; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D019172:Transplantation Conditioning
chemical_list: D008558:Melphalan