Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial.
Arsenic trioxide (ATO) is synergistic with ascorbic acid (AA) and melphalan against myeloma both in vitro and in vivo. The aim of this randomized phase II trial was to determine the safety and efficacy of a combination of ATO, melphalan, and AA as preparative regimen in 48 patients undergoing autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM). Forty-eight patients received melphalan 200 mg/m2 i.v. over 2 days and AA 1000 mg i.v. over 7 days in 3 treatment arms: no ATO (arm 1), ATO 0.15 mg/kg i.v. x 7 days (arm 2), and ATO 0.25 mg/kg i.v. x 7 days (arm 3). No dose-limiting toxicity, engraftment failure, or nonrelapse mortality (NRM) was seen in the first 100 days post-ASCT. Complete responses (CR) were seen in 12 of 48 patients (25%), with an overall response rate (ORR = CR + PR) of 85%. Median progression-free survival (PFS) was 25 months; median overall survival (OS) has not yet been reached. There was no significant difference in CR, PFS, or OS among the 3 treatment arms, and no adverse effect of ATO on melphalan pharmacokinetics. Addition of ATO + AA to high-dose melphalan is safe and well tolerated as a preparative regimen for MM.
Qazilbash
Muzaffar H
MH
Department of Stem Cell Transplantation and Cellular Therapy, UT M.D. Anderson Cancer Center, Houston, Texas 77030, USA. mqazilba@mdanderson.org
Saliba
Rima M
RM
Nieto
Yago
Y
Parikh
Gaurav
G
Pelosini
Matteo
M
Khan
Fatima B
FB
Jones
Roy B
RB
Hosing
Chitra
C
Mendoza
Floralyn
F
Weber
Donna M
DM
Wang
Michael
M
Popat
Uday
U
Alousi
Amin
A
Anderlini
Paolo
P
Champlin
Richard E
RE
Giralt
Sergio
S
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010087:Oxides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D000975:Antioxidants; D001152:Arsenicals; D019653:Myeloablative Agonists; D010087:Oxides; D001205:Ascorbic Acid; D008558:Melphalan; D000077237:Arsenic Trioxide