title: Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study.
abstract: We assessed the safety and efficacy of melphalan, arsenic trioxide (ATO) and ascorbic acid (AA) (MAC) combination therapy for patients with multiple myeloma (MM) who failed more than two different prior regimens. Patients received melphalan (0.1 mg/kg p.o.), ATO (0.25 mg/kg i.v.) and AA (1 g i.v) on days 1-4 of week 1, ATO and AA twice weekly during weeks 2-5 and no treatment during week 6 of cycle 1; during cycles 2-6, the schedule remained the same except ATO and AA were given twice weekly in week 1. Objective responses occurred in 31 of 65 (48%) patients, including two complete, 15 partial and 14 minor responses. Median progression-free survival and overall survival were 7 and 19 months respectively. Twenty-two patients had elevated serum creatinine levels (SCr) at baseline, and 18 of 22 (82%) showed decreased SCr levels during treatment. Specific grade 3/4 haematological (3%) or cardiac adverse events occurred infrequently. Frequent grade 3/4 non-haematological adverse events included fever/chills (15%), pain (8%) and fatigue (6%). This steroid-free regimen was effective and well tolerated in this heavily pretreated group. These results indicate that the MAC regimen is a new therapeutic option for patients with relapsed or refractory MM.
authors.affiliation: Institute for Myeloma and Bone Cancer Research, West Hollywood, CA 90069, USA. jberenson@imbcr.org
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.forename: Marek
authors.initials: M
authors.lastname: Bozdech
authors.forename: Alberto
authors.initials: A
authors.lastname: Bessudo
authors.forename: Edward
authors.initials: E
authors.lastname: Stadtmauer
authors.forename: J
authors.initials: J
authors.lastname: Talisman Pomeroy
authors.forename: Ronald
authors.initials: R
authors.lastname: Steis
authors.forename: Marshall
authors.initials: M
authors.lastname: Flam
authors.forename: Jose
authors.initials: J
authors.lastname: Lutzky
authors.forename: Syed
authors.initials: S
authors.lastname: Jilani
authors.forename: Joseph
authors.initials: J
authors.lastname: Volk
authors.forename: Siu-Fun
authors.initials: SF
authors.lastname: Wong
authors.forename: Robert
authors.initials: R
authors.lastname: Moss
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Delina
authors.initials: D
authors.lastname: Ferretti
authors.forename: Kit
authors.initials: K
authors.lastname: Russell
authors.forename: Robert
authors.initials: R
authors.lastname: Louie
authors.forename: Howard S
authors.initials: HS
authors.lastname: Yeh
authors.forename: Regina A
authors.initials: RA
authors.lastname: Swift
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001152:Arsenicals; D010087:Oxides; D003404:Creatinine; D001205:Ascorbic Acid; D008558:Melphalan; D000077237:Arsenic Trioxide