|
|
 Previous Article | Table of Contents | Next Article 
Multidrug-resistant myeloma: laboratory and clinical effects of verapamil
as a chemosensitizer
SE Salmon, WS Dalton, TM Grogan, P Plezia, M Lehnert, DJ Roe and TP Miller
Arizona Cancer Center, Tucson 85724.
Verapamil was evaluated as a chemosensitizer for reversing multidrug
resistance in multiple myeloma both in vitro and in clinical trials. Bone
marrows from 59 myeloma patients in relapse were evaluated for several
resistance parameters: expression of p-glycoprotein (MDR1), doxorubicin
(Adriamycin) and vincristine sensitivity, and the ability of added
verapamil to reduce resistance to the cytotoxic agents. We found that
verapamil was capable of sensitizing myeloma cells that exhibited
resistance to doxorubicin and vincristine in vitro, but did not enhance
sensitivity of cells that were drug sensitive (P less than .001). Myeloma
cells expressing MDR1 immunohistochemically tended to be more doxorubicin
resistant in vitro than MDR1-negative cells. In the clinical trials, 22
patients with myeloma refractory to vincristine- Adriamycin-dexamethasone
(VAD) were treated with VAD plus high-dose intravenous verapamil (Ve).
Among the 22 patients treated with VAD/Ve, five achieved a partial
remission (23%). The median relapse-free survival for the VAD/Ve responders
was 5.4 months and their overall survival from the start of VAD/Ve was
better than that of the nonresponders. Among the subset of 10 patients
whose myeloma cells were MDR1 positive, four responded clinically (40%),
whereas none of five patients with MDR1-negative myeloma cells achieved
remission with VAD/Ve. We also observed that myeloma cells from three of
four VAD/Ve clinical responders exhibited in vitro chemosensitization with
verapamil, whereas in vitro verapamil chemosensitization was seen in only
one of six clinical nonresponders. Our observations demonstrate that
clinical reversal of multidrug resistance can be achieved in some patients
with VAD-refractory myeloma with the use of verapamil. In addition to their
value in drug development, in vitro tests of MDR1 expression and of
chemosensitizers plus cytotoxic drugs on the patients' bone marrow myeloma
cells may identify patients who will respond clinically to
chemosensitizer-containing regimens. We anticipate that chemosensitizer
regimens capable of inhibiting multidrug resistance will play an increasing
role in the treatment of hematologic malignancies, including B-cell
neoplasms such as multiple myeloma and the non-Hodgkin's lymphomas.
Volume 78,
Issue 1,
pp. 44-50,
07/01/1991
Copyright © 1991 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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]
|
|
|
|
|
|
|
M. C. Zatelli, A. Luchin, D. Piccin, F. Tagliati, A. Bottoni, C. Vignali, M. Bondanelli, and E. C. degli Uberti
Cyclooxygenase-2 Inhibitors Reverse Chemoresistance Phenotype in Medullary Thyroid Carcinoma by a Permeability Glycoprotein-Mediated Mechanism
J. Clin. Endocrinol. Metab.,
October 1, 2005;
90(10):
5754 - 5760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yasui, T. Hideshima, M. Hamasaki, A. M. Roccaro, N. Shiraishi, S. Kumar, P. Tassone, K. Ishitsuka, N. Raje, Y.-T. Tai, et al.
SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma
Blood,
July 15, 2005;
106(2):
706 - 712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hamasaki, T. Hideshima, P. Tassone, P. Neri, K. Ishitsuka, H. Yasui, N. Shiraishi, N. Raje, S. Kumar, D. H. Picker, et al.
Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo
Blood,
June 1, 2005;
105(11):
4470 - 4476.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hideshima, D. Chauhan, T. Hayashi, K. Podar, M. Akiyama, C. Mitsiades, N. MItsiades, B. Gong, L. Bonham, P. de Vries, et al.
Antitumor Activity of Lysophosphatidic Acid Acyltransferase-{beta} Inhibitors, a Novel Class of Agents, in Multiple Myeloma
Cancer Res.,
December 1, 2003;
63(23):
8428 - 8436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Grad, N. J. Bahlis, I. Reis, M. M. Oshiro, W. S. Dalton, and L. H. Boise
Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells
Blood,
August 1, 2001;
98(3):
805 - 813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.L. Smith and A.C. Newland
Treatment of myeloma
QJM,
January 1, 1999;
92(1):
11 - 14.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Pilarski, A. J. Szczepek, and A. R. Belch
Deficient Drug Transporter Function of Bone Marrow-Localized and Leukemic Plasma Cells in Multiple Myeloma
Blood,
November 1, 1997;
90(9):
3751 - 3759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Bataille and J.-L. Harousseau
Multiple Myeloma
N. Engl. J. Med.,
June 5, 1997;
336(23):
1657 - 1664.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Szczepek, P.L. Bergsagel, L. Axelsson, C. B. Brown, A. R. Belch, and L. M. Pilarski
CD34+ Cells in the Blood of Patients With Multiple Myeloma Express CD19 and IgH mRNA and Have Patient-Specific IgH VDJ Gene Rearrangements
Blood,
March 1, 1997;
89(5):
1824 - 1833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Bates, W. H. Wilson, A. T. Fojo, M. Alvarez, Z. Zhan, J. Regis, R. Robey, C. Hose, A. Monks, Y. K. Kang, et al.
Clinical Reversal of Multidrug Resistance
Oncologist,
August 1, 1996;
1(4):
269 - 275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bates, W. Wilson, A. Fojo, M Alvarez, Z Zhan, J Regis, R Robey, C Hose, A Monks, Y. Kang, et al.
Clinical reversal of multidrug resistance
Stem Cells,
January 1, 1996;
14(1):
56 - 63.
[Abstract]
|
|
|
|
|
|
|
N. Baldini, K. Scotlandi, G. Barbanti-Brodano, M. C. Manara, D. Maurici, G. Bacci, F. Bertoni, P. Picci, S. Sottili, M. Campanacci, et al.
Expression of P-Glycoprotein in High-Grade Osteosarcomas in Relation to Clinical Outcome
N. Engl. J. Med.,
November 23, 1995;
333(21):
1380 - 1385.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
