This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berenson, J. R. Articles by Yeh, H. S. Search for Related Content PubMed PubMed Citation Articles by Berenson, J. R. Articles by Yeh, H. S.

A Phase I/II Study of Arsenic Trioxide/Bortezomib/Ascorbic Acid Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma

Authors' Affiliations: ¹ Institute for Myeloma and Bone Cancer Research and ² Oncotherapeutics, Inc., West Hollywood, California; ³ Rocky Mountain Cancer Centers, Denver, Colorado; and ⁴ Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts

Requests for reprints: James R. Berenson, Institute for Myeloma and Bone Cancer Research, Suite 300, 9201 West Sunset Boulevard, West Hollywood, CA 90069. Phone: 310-623-1214; Fax: 310-623-1120; E-mail: jberenson{at}imbcr.org.

Purpose: This multicenter, open-label, phase I/II dose escalation study assessed the safety/tolerability and initial efficacy of arsenic trioxide/bortezomib/ascorbic acid (ABC) combination therapy in patients with relapsed/refractory multiple myeloma.

Experimental Design: Enrolled in six cohorts, patients were given arsenic trioxide (0.125 or 0.250 mg/kg), bortezomib (0.7, 1.0, or 1.3 mg/m²), and a fixed dose of ascorbic acid (1 g) i.v. on days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles. The primary end point was safety/tolerability of the ABC regimen.

Results: Twenty-two patients (median age, 63 years) were enrolled, having failed a median of 4 (range, 3-9) prior therapies. One occurrence of grade 4 thrombocytopenia was observed. One patient had asymptomatic arrhythmia and withdrew from the study. Objective responses were observed in 6 (27%) patients, including two partial responses and four minor responses. Median progression-free survival was 5 months (95% confidence interval, 2-9 months), and median overall survival had not been reached. The 12-month progression-free survival and overall survival rates were 34% and 74%, respectively. One (minor response) of six patients receiving the lowest dose of bortezomib (0.7 mg/m²) and 5 (2 partial responses and 3 minor responses) of 16 patients receiving the higher doses (1.0 or 1.3 mg/m²) responded.

Conclusions: The ABC regimen was well tolerated by most patients, and it produced preliminary signs of efficacy with an objective response rate of 27% in this heavily pretreated study population. These findings warrant further clinical evaluation of the ABC combination for treatment of relapsed/refractory multiple myeloma.

This article has been cited by other articles:

				P. Lunghi, N. Giuliani, L. Mazzera, G. Lombardi, M. Ricca, A. Corradi, A. M. Cantoni, L. Salvatore, R. Riccioni, A. Costanzo, et al. Targeting MEK/MAPK signal transduction module potentiates ATO-induced apoptosis in multiple myeloma cells through multiple signaling pathways Blood, September 15, 2008; 112(6): 2450 - 2462. [Abstract] [Full Text] [PDF]

				A. A. Morales, D. Gutman, K. P. Lee, and L. H. Boise BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma Blood, May 15, 2008; 111(10): 5152 - 5162. [Abstract] [Full Text] [PDF]

				P. G. Richardson, C. Mitsiades, R. Schlossman, N. Munshi, and K. Anderson New Drugs for Myeloma Oncologist, June 1, 2007; 12(6): 664 - 689. [Abstract] [Full Text] [PDF]