Multidrug Resistance Reversal Agents

Journal of Medicinal Chemistry

Volumn 46, Issue 23, 2003, Pages 4805-4817

  Robert, Jacques ^a,b   Jarry, Christian ^b  

^a INSTITUT BERGONIÉ   (France)

^b UNIVERSITÉ DE BORDEAUX   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 BIS(ALLYLAMINO) 6 [4 [[2,2 BIS(4 FLUOROPHENYL)ETHYL]AMINO]PIPERIDINO] 1,3,5 TRIAZINE; 5 [3 (4 DIPHENYLACETYL 1 PIPERAZINYL) 2 HYDROXYPROPOXY]QUINOLINE; AMIODARONE; ANTHRACYCLINE DERIVATIVE; ANTINEOPLASTIC AGENT; BEPRIDIL; BIBW 22BS; BIRICODAR; CINCHONINE; CYCLOSPORIN A; DEXNIGULDIPINE; DEXVERAPAMIL; DIPYRIDAMOLE; DOXORUBICIN; ELACRIDAR; FLUPENTIXOL; GLYCOPROTEIN P; MULTIDRUG RESISTANCE INHIBITOR; MULTIDRUG RESISTANCE PROTEIN; NIFEDIPINE; PROGESTERONE; QUINIDINE; QUININE; TAMOXIFEN; TARIQUIDAR; TAXANE DERIVATIVE; TOREMIFENE; TRIFLUOPERAZINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALSPODAR; VERAPAMIL; VINBLASTINE; ZOSUQUIDAR;

ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; BINDING SITE; CANCER; CANCER COMBINATION CHEMOTHERAPY; CARDIOTOXICITY; CLINICAL TRIAL; CROSS RESISTANCE; DRUG DESIGN; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; HUMAN; MULTIDRUG RESISTANCE; NEUROTOXICITY; ONCOLOGY; PHARMACOPHORE; PROTEIN DOMAIN; PROTEIN FUNCTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW;

EID: 0242331085     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030183a     Document Type: Review

References (151)

1. Avendano, C.; Menendez, J. C. Inhibitors of multidrug resistance to antitumor agents (MDR). Curr. Med. Chem. 2002, 9, 159-193.
2. Gottesman, M. M. Mechanisms of cancer drug resistance. Annu. Rev. Med. 2002, 53, 615-627.
3. Robert, J. Multidrug resistance in oncology: diagnostic and therapeutic approaches. Eur. J. Clin. Invest. 1999, 29, 536-545.
4. Sikic, B. I.; Fisher, G. A.; Lum, B. L.; Halsey, J.; Beketic-Oreskovic, L.; Chen, G. Modulation and prevention of multidrug resistance by inhibitors of P-glycoprotein. Cancer Chemother. Pharmacol. 1997, 40 (Suppl.), S13-S19.
5. Wiese, M.; Pajeva, I. K. Structure-activity relationships of multidrug resistance reversers. Curr. Med. Chem. 2001, 8, 685-713.
6. Ford, J. M.; Hait, W. N. Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol. Rev. 1990, 42, 155-199.
7. Beck, W. T.; Grogan, T. M.; Willman, C. L.; Cordon-Cardo, C.; Parham, D. M.; Kuttesch, J. F.; et al. Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations. Cancer Res. 1996, 56, 3010-3020.
8. Chevillard, S.; Vielh, P.; Validire, P.; Marie, J. P.; Faussat, A. M.; Barbu, V.; et al. French multicentric evaluation of MDR1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris. Leukemia 1997, 11, 1095-1106.
9. Huet, S.; Marie, J. P.; Gualde, N.; Robert, J. Reference method for detection of Pgp mediated multidrug resistance in human hematological malignancies: a method validated by the laboratories of the French Drug Resistance Network. Cytometry 1998, 34, 248-256.
10. Marie, J. P.; Huet, S.; Faussat, A. M.; Perrot, J. Y.; Chevillard, S.; Barbu, V.; et al. Multicentric evaluation of the MDR phenotype in leukemia. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hopitaux de Paris. Leukemia 1997, 11, 1086-1094.
11. Gianni, L.; Munzone, E.; Capri, G.; Fulfaro, F.; Tarenzi, E.; Villani, F.; et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J. Clin. Oncol. 1995, 13, 2688-2699.
12. Yuen, A. R.; Sikic, B. I. Multidrug resistance in lymphomas. J. Clin. Oncol. 1994, 12, 2453-2459.
13. Kao, C. H.; Tsai, S. C.; Wang, J. J.; Ho, Y. J.; Ho, S. T.; Changlai, S. P. Technetium-99m-sestamethoxyisobutylisonitrile scan as a predictor of chemotherapy response in malignant lymphomas compared with P-glycoprotein expression, multidrug resistance-related protein expression and other prognosis factors. Br. J. Haematol. 2001, 113, 369-374.
14. Leith, C. P.; Kopecky, K. J.; Godwin, J.; McConnell, T.; Slovak, M. L.; Chen, I. M.; et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 1997, 89, 3323-3329.
15. Leith, C. P.; Kopecky, K. J.; Chen, I. M.; Eijdems, L.; Slovak, M. L.; McConnell, T. S.; et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/ P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood 1999, 94, 1086-1099.
16. Bellamy, W. T.; Odeleye, A.; Finley, P.; Huizenga, B.; Dalton, W. S.; Weinstein, R. S.; et al. An in vivo model of human multidrug-resistant multiple myeloma in SCID mice. Am. J. Pathol. 1993, 142, 691-698.
17. Leveille-Webster, C. R.; Arias, I. A. Establishment and serial quantification of intrahepatic xenografts of human hepatocellular carcinoma in severe combined immunodeficiency mice, and development of therapeutic strategies to overcome multidrug resistance. Clin. Cancer Res. 1996, 2, 695-706.
18. van de Vrie, W.; Marquet, R. L.; Stoter, G.; De Bruijn, E. A.; Eggermont, A. M. In vivo model systems in P-glycoprotein-mediated multidrug resistance. Crit. Rev Clin. Lab. Sci. 1998, 35, 1-57.
19. Galski, H.; Sullivan, M.; Willingham, M. C.; Chin, K. V.; Gottesman, M. M.; Pastan, I.; et al. Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia. Mol. Cell. Biol. 1989, 9, 4357-4363.
20. Mickisch, G. H.; Merlino, G. T.; Galski, H.; Gottesman, M. M.; Pastan, I. Transgenic mice that express the human multidrug-resistance gene in bone marrow enable a rapid identification of agents that reverse drug resistance. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 547-551.
21. Mickisch, G. H.; Pastan, I.; Gottesman, M. M. Multidrug resistant transgenic mice as a novel pharmacologic tool. Bio-Essays 1991, 13, 381-387.
22. Mickisch, G. H.; Rahman, A.; Pastan, I.; Gottesman, M. M. Increased effectiveness of liposome-encapsulated doxorubicin in multidrug-resistant-transgenic mice compared with free doxorubicin. J. Natl. Cancer Inst. 1992, 84, 804-805.
23. Evans, G. L. Construction and analysis of multidrug resistance transgenic mice. Methods Enzymol. 1998, 292, 572-594.
24. Thiebaut, F.; Tsuruo, T.; Hamada, H.; Gottesman, M. M.; Pastan, I.; Willingham, M. C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 7735-7738.
25. Schinkel, A. H.; Smit, J. J.; van Tellingen, O; Beijnen, J. H.; Wagenaar, E.; van Deemter, L.; et al. Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994, 77, 491-502.
26. Wilson, W. H.; Bates, S. E.; Fojo, A.; Bryant, G.; Zhan, Z.; Regis, J.; et al. Controlled trial of dexverapamil, a modulator of multidrug resistance, in lymphomas refractory to EPOCH chemotherapy. J. Clin. Oncol. 1995, 13, 1995-2004.
27. Hyafil, F.; Vergely, C.; Du, V. P.; Grand-Perret, T. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res. 1993, 53, 4595-4602.
28. Sato, W.; Fukazawa, N.; Nakanishi, O.; Baba, M.; Suzuki, T.; Yano, O.; et al. Reversal of multidrug resistance by a novel quinoline derivative, MS-209. Cancer Chemother. Pharmacol. 1995, 35, 271-277.
29. Safa, A. R. Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 7187-7191.
30. Safa, A. R.; Mehta, N. D.; Agresti, M. Photoaffinity labeling of P-glycoprotein in multidrug resistant cells with photoactive analogs of colchicine. Biochem. Biophys. Res. Commun. 1989, 162, 1402-1408.
31. Bruggemann, E. P.; Germann, U. A.; Gottesmann, M. M.; Pastan, I. Two different regions of P-glycoprotein are photoaffinity-labeled by azidopine. J. Biol. Chem. 1989, 264, 15483-15488.
32. Demmer, A.; Thole, H.; Kubesch, P.; Brandt, T.; Raida, M.; Fislage, R.; Tummler, B. Localization of the iodomycin binding site in hamster P-glycoprotein. J. Biol. Chem. 1997, 272, 20913-20919.
33. Greenberger, L. M. Major photoaffinity drug labeling sites for iodoaryl azidoprazosin in P-glycoprotein are within, or immediately C-terminal to, transmembrane domain-6 and domain-12. J. Biol. Chem. 1993, 268, 11417-11425.
34. Morris, D. I.; Greenberger, L. M.; Bruggemann, E. P.; Cardarelli, C.; Gottesman, M. M.; Pastan, I.; Seamon, K. B. Localization of the forskolin labeling sites to both halves of P-glycoprotein: similarity of the sites labeled by forskolin and prazosin. Mol. Pharmacol. 1994, 46, 329-337.
35. Loo, T. W.; Clarke, D. M. The transmembrane domains of the human multidrug resistance P-glycoprotein are sufficient to mediate drug binding and trafficking to the cell surface. J. Biol. Chem. 1999, 274, 24759-24765.
36. Ambudkar, S. V.; Dey, S.; Hrycyna, C. A.; Ramachandra, M.; Pastan, I.; Gottesman, M. M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 1999, 39, 361-398.
37. Loo, T. W.; Clarke, D. M. Molecular dissection of the human multidrug resistance P-glycoprotein. Biochem. Cell. Biol. 1999, 77, 11-23.
38. Loo, T. W.; Clarke, D. M. Inhibition of oxidative cross-linking between engineered cysteine residues at positions 332 in predicted transmembrane segment (TM) 6 and 975 in predicted TM12 of human P-glycoprotein by drug substrates. J. Biol. Chem. 1996, 271, 27482-27487.
39. Loo, T. W.; Clarke, D. M. Identification of residues within the drug-binding domain of the human multidrug resistance p-glycoprotein by cysteine-scanning mutagenesis and reaction with dibromobimane. J. Biol. Chem. 2000, 275, 39272-39278.
40. Shapiro, A. B.; Ling, V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. Eur. J. Biochem. 1997, 250, 130-137.
41. Shapiro, A. B.; Fox, K.; Lam, P.; Ling, V. Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone-evidence for a third drug-binding site. Eur. J. Biochem. 1999, 259, 841-850.
42. Pascaud, C.; Garrigos, M.; Orlowski, S. Multidrug resistance transporter P-glycoprotein has distinct but interacting binding sites for cytotoxic drugs and reversing agents. Biochem. J. 1998, 333, 351-358.
43. Garrigues, A.; Loiseau, N.; Delaforge, M.; Ferte, J.; Garrigos, M.; Andre, F.; Orlowski, S. Characterization of two pharmacophores on the multidrug transporter P-glycoprotein. Mol. Pharmacol. 2002, 62, 1288-1298.
44. Loo, T. W.; Clarke, D. M. Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methane-sulfonate analog of verapamil, MTS-verapamil. J. Biol. Chem. 2001, 276, 14972-14979.
45. Loo, T. W.; Clarke, D. M. Location of the rhodamine-binding site in the human multidrug resistance P-glycoprotein. J. Biol. Chem. 2002, 277, 44332-44338.
46. Loo, T. W.; Clarke, D. M. The packing of the transmembrane segments of human multidrug resistance P-glycoprotein is revealed by disulfide cross-linking analysis. J. Biol. Chem. 2000, 275, 5253-5256.
47. Loo, T. W.; Clarke, D. M. Drug-stimulated ATPase activity of human P-glycoprotein is blocked by disulfide cross-linking between the nucleotide-binding sites. J. Biol. Chem. 2000, 275, 19435-19438.
48. Loo, T. W.; Clarke, D. M. Determining the dimensions of the drug-binding domain ofhuman P-glycoprotein using thiol cross-linking compounds as molecular rulers. J. Biol. Chem. 2001, 276, 36877-36880.
49. Senior, A. E. Catalytic mechanism of P-glycoprotein. Acta Physiol. Scand. 1998, 163, 213-218.
50. Zamora, J. M.; Pearse, H. L.; Beck, W. T. Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells. Mol. Pharmacol. 1988, 33, 454-462.
51. Stouch, T. R.; Gudmundsson, A. Progress in understanding the structure-activity relationships of P-glycoprotein. Adv. Drug Delivery Rev. 2002, 54, 315-328.
52. Seelig, A. A general pattern for substrate recognition by P-glycoprotein. Eur. J. Biochem. 1998, 251, 252-261.
53. Seelig, A.; Landwojtowicz, E. Structure-activity relationship of P-glycoprotein substrates and modifiers. Eur. J. Pharm. Sci. 2000, 12, 31-40.
54. Scala, S.; Akhmed, N.; Rao, U. S.; Paull, K.; Lan, L. B.; Dickstein, B.; Lee J. S.; et al. P-glycoprotein substrates and antagonists cluster into two distinct groups. Mol. Pharmacol. 1997, 51, 1024-1033.
55. Klopman, G.; Shi, L. M.; Ramu, A. Quantitative structure-activity relationship of multidrug resistance reversal agents. Mol. Pharmacol. 1997, 52, 323-334.
56. Bakken, G. A.; Jurs, P. C. Classification of multidrug-resistance reversal agents using structure-based descriptors and linear discriminant analysis. J. Med. Chem. 2000, 43, 4534-4541.
57. Ekins, S.; Kim, R. B.; Leake, B. F.; Dantzig, A. H.; Schuetz, E. G.; Lan, L. B.; et al. Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol. Pharmacol. 2002, 61, 964-973.
58. Pajeva, I. K.; Wiese, M. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J. Med. Chem. 2002, 45, 5671-5686.
59. Ozols, R. F.; Cunnion, R. E.; Klecker, R. W. J.; Hamilton, T. C.; Ostchega, Y.; Parrillo, J. E.; et al. Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J. Clin. Oncol. 1987, 5, 641-647.
60. Dalton, W. S.; Grogan, T. M.; Meltzer, P. S.; Scheper, R. J.; Durie, B. G.; Taylor, C. W.; et al. Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J. Clin. Oncol. 1989, 7, 415-424.
61. Durie, B. G.; Dalton, W. S. Reversal of drug-resistance in multiple myeloma with verapamil. Br. J. Haematol. 1988, 68, 203-206.
62. Miller, T. P.; Grogan, T. M.; Dalton, W. S.; Spier, C. M.; Scheper, R. J.; Salmon, S. E. P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J. Clin. Oncol. 1991, 9, 17-24.
63. Salmon, S. E.; Dalton, W. S.; Grogan, T. M.; Plezia, P.; Lehnert, M.; Roe, D. J.; et al. Multidrug-resistant myeloma: laboratory and clinical effects of verapamil as a chemosensitizer. Blood 1991, 78, 44-50.
64. Dalton, W. S.; Crowley, J. J.; Salmon, S. S.; Grogan, T. M.; Laufman, L. R.; Weiss, G. R.; et al. A phase III randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in patients with refractory myeloma. A Southwest Oncology Group study. Cancer 1995, 75, 815-820.
65. Demicheli, R.; Jirillo, A.; Bonciarelli, G.; Lonardi, F.; Balli, M.; Bandello, A. 4′-Epidoxorubicin plus verapamil in anthracycline-refractory cancer patients. Tumori 1989, 75, 245-247.
66. Langenbuch, T.; Mross, K.; Jonat, W.; Hossfeld, D. K. A phase II study of intensive-dose epirubicin/verapamil as induction therapy followed by intensive-dose ifosfamide for advanced breast cancer. Cancer Chemother. Pharmacol. 1990, 26 (Suppl.), S93-S96.
67. Mross, K.; Bohn, C.; Edler, L.; Jonat, W.; Queisser, W.; Heidemann, E.; et al. Randomized phase II study of single-agent epirubicin ± verapamil in patients with advanced metastatic breast cancer. An AIO clinical trial. Arbeitsgemeinschaft Internistische Onkologie of the German Cancer Society. Ann. Oncol. 1993, 4, 45-50.
68. Cairo, M. S.; Siegel, S.; Anas, N.; Sender, L. Clinical trial of continuous infusion verapamil, bolus vinblastine, and continuous infusion VP-16 in drug-resistant pediatric tumors. Cancer Res. 1989, 49, 1063-1066.
69. Millward, M. J.; Cantwell, B. M.; Lien, E. A.; Carmichael, J.; Harris, A. L. Intermittent high-dose tamoxifen as a potential modifier of multidrug resistance. Eur. J. Cancer 1992, 28A, 805-810.
70. Belpomme, D.; Gauthier, S.; Pujade-Lauraine, E.; Facchini, T.; Goudier, M. J.; Krakowski, I.; et al. Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma. Ann. Oncol. 2000, 11, 1471-1476.
71. Bissett, D.; Kerr, D. J.; Cassidy, J.; Meredith, P.; Traugott, U.; Kaye, S. B. Phase I and pharmacokinetic study of D-verapamil and doxorubicin. Br. J. Cancer 1991, 64, 1168-1171.
72. Lehnert, M.; Mross, K.; Schueller, J.; Thuerlimann, B.; Kroeger, N.; Kupper, H. Phase II trial of dexverapamil and epirubicin in patients with non-responsive metastatic breast cancer. Br. J. Cancer 1998, 77, 1155-1163.
73. Scheithauer, W.; Kornek, G.; Kastner, J.; Raderer, M.; Locker, G.; Depisch, D.; et al. Phase II study of D-verapamil and doxorubicin in patients with metastatic colorectal cancer. Eur. J. Cancer 1993, 29A, 2337-2338.
74. Motzer, R. J.; Lyn, P.; Fischer, P.; Lianes, P.; Ngo, R. L.; Cordon-Cardo, C.; et al. Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma. J. Clin. Oncol. 1995, 13, 1958-1965.
75. Warner, E.; Hedley, D.; Andrulis, I.; Myers, R.; Trudeau, M.; Warr, D.; et al. Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen. Clin. Cancer Res. 1998, 4, 1451-1457.
76. Fisher, G. A.; Bartlett, N. L.; Lum, N. A.; Brophy, N. A.; Duran, G. E.; Ehsan, M. N.; et al. Phase I trial of Taxol with high-dose cyclosporin A as a modulator of multidrug resistance. Proc. Am. Soc. Clin. Oncol. 1994, 13, 144, Abstr. 369.
77. Lum, B. L.; Kaubisch, S.; Yahanda, A. M.; Adler, K. M.; Jew, L.; Ehsan, M. N.; et al. Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J. Clin. Oncol. 1992, 10, 1635-1642.
78. Rushing, D. A.; Raber, S. R.; Rodvold, K. A.; Piscitelli, S. C.; Plank, G. S.; Tewksbury, D. A. The effects of cyclosporine on the pharmacokinetics of doxorubicin in patients with small cell lung cancer. Cancer 1994, 74, 834-841.
79. Sonneveld, P.; Durie, B. G.; Lokhorst, H. M.; Marie, J. P.; Solbu, G.; Suciu, S.; et al. Modulation of multidrug-resistant multiple myeloma by cyclosporin. The Leukaemia Group of the EORTC and the HOVON. Lancet 1992, 340, 255-259.
80. List, A. F.; Spier, C.; Greer, J.; Wolff, S.; Hutter, J.; Dorr, R.; et al. Phase I/II trial of cyclosporine asa chemotherapy-resistance modifier in acute leukemia. J. Clin. Oncol. 1993, 11, 1652-1660.
81. Verweij, J.; Herweijer, H.; Oosterom, R.; van der Burg, M. E.; Planting, A. S.; Seynaeve, C.; et al. A phase II study of epidoxorubicin in colorectal cancer and the use of cyclosporin-A in an attempt to reverse multidrug resistance. Br. J. Cancer 1991, 64, 361-364.
82. Rodenburg, C. J.; Nooter, K.; Herweijer, H.; Seynaeve, C.; Oosterom, R.; Stoter, G.; et al. Phase II study of combining vinblastine and cyclosporin-A to circumvent multidrug resistance in renal cell cancer. Ann. Oncol. 1991, 2, 305-306.
83. Sarris, A. H.; Younes, A.; McLaughlin, P.; Moore, D.; Hagemeister, F.; Swan, F.; et al. Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with relapsed non-Hodgkin's lymphoma. J. Clin. Oncol. 1996, 14, 233-239.
84. Sonneveld, P.; Suciu, S.; Weijermans, P.; Beksac, M.; Neuwirtova, R.; Solbu, G.; et al. Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC-HOVON randomized phase III study (06914). Br. J. Haematol. 2001, 115, 895-902.
85. List, A. F.; Kopecky, K. J.; Willman, C. L.; Head, D. R.; Persons, D. L. ; Slovak, M. L.; et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood 2001, 98, 3212-3220.
86. Dahl, G. V.; Lacayo, N. J.; Brophy, N.; Dunussi-Joannopoulos, K.; Weinstein, H. J.; Chang, M.; et al. Mitoxantrone, etoposide, and cyclosporine therapy in pediatric patients with recurrent or refractory acute myeloid leukemia. J. Clin. Oncol. 2000, 18, 1867-1875.
87. Liu, Y. J.; Wheatley, K.; Rees, J. K.; Burnett, A. K. Comparison of "sequential" versus "standard" chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): results of the UK Medical Research Council AML-R trial. Br. J. Haematol. 2001, 113, 713-726.
88. Tallman, M. S.; Lee, S.; Sikic, B. I.; Paietta, E.; Wiernik, P. H.; Bennett, J. M.; et al. Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia: an Eastern Cooperative Oncology Group pilot study. Cancer 1999, 85, 358-367.
89. Twentyman, P. R.; Bleehen, N. M. Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin. Eur. J. Cancer 1991, 27, 1639-1642.
90. Boesch, D.; Gaveriaux, C.; Jachez, B.; Pourtier-Manzanedo, A.; Bollinger, P.; Loor, F. In vivo circumvention of P-glycoprotein-mediated multidrug resistance of tumor cells with SDZ PSC 833. Cancer Res. 1991, 51, 4226-4233.
91. Boote, D. J.; Dennis, I. F.; Twentyman, P. R.; Osborne, R. J.; Laburte, C.; Hensel, S.; et al. Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J. Clin. Oncol. 1996, 14, 610-618.
92. Giaccone, G.; Linn, S. C.; Welink, J.; Catimel, G.; Stieltjes, H.; van der Vijgh, W. J.; et al. A dose-finding and pharmacokinetic study of reversal of multidrug resistance with SDZ PSC 833 in combination with doxorubicin in patients with solid tumors. Clin. Cancer Res. 1997, 3, 2005-2015.
93. Advani, R.; Saba, H. I.; Tallman, M. S.; Rowe, J. M.; Wiernik, P. H.; Ramek, J.; et al. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood 1999, 93, 787-795.
94. Fracasso, P. M.; Westervelt, P.; Fears, C. L.; Rosen, D. M.; Zuhowski, E. G.; Cazenave, L. A.; et al. Phase I study of paclitaxel in combination with a multidrug resistance modulator, PSC 833 (Valspodar), in refractory malignancies. J. Clin. Oncol. 2000, 18, 1124-1134.
95. Chauncey, T. R.; Rankin, C.; Anderson, J. E.; Chen, I.; Kopecky, K. J.; Godwin, J. E.; et al. A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617. Leuk. Res. 2000, 24, 567-574.
96. Dorr, R.; Karanes, C.; Spier, C.; Grogan, T.; Greer, J.; Moore, J.; et al. Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia. J. Clin. Oncol. 2001, 19, 1589-1599.
97. Lee, E. J.; George, S. L.; Caligiuri, M.; Szatrowski, T. P.; Powell, B. L.; Lemke, S.; et al. Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia: results of cancer and leukemia group B study 9420. J. Clin. Oncol. 1999, 17, 2831-2839.
98. Visani, G.; Milligan, D.; Leoni, F.; Chang, J.; Kelsey, S.; Marcus, R.; et al. Combined action of PSC 833 (Valspodar), a novel MDR reversing agent, with mitoxantrone, etoposide and cytarabine in poor-prognosis acute myeloid leukemia. Leukemia 2001, 15, 764-771.
99. Baer, M. R.; George, S. L.; Dodge, R. K.; O'Loughlin, K. L.; Minderman, H.; Caligiuri, M. A.; et al. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: cancer and leukemia group B study 9720. Blood 2002, 100, 1224-1232.
100. Greenberg, P.; Advani, R.; Tallman, M.; Letendre, L.; Saba, H.; Dugan, K.; et al. Treatment of refractory/relapsed AML with PSC-833 plus mitoxantrone, etoposide, cytarabine (PSC-MEC) vs MEC: randomized phase III trial (E2995). Blood 1999, 94, 383a (Abstract 1703).
101. Fracasso, P. M.; Brady, M. F.; Moore, D. H.; Walker, J. L.; Rose, P. G.; Letvak, L.; et al. Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study. J. Clin. Oncol. 2001, 19, 2975-2982.
102. Baekelandt, M.; Lehne, G.; Trope, C. G.; Szanto, I.; Pfeiffer, P.; Gustavssson, B.; et al. Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer. J. Clin. Oncol. 2001, 19, 2983-2993.
103. Bates, S.; Kang, M.; Meadows, B.; Bakke, S.; Choyke, P.; Merino, M.; et al. A phase I study of infusional vinblastine in combination with the P-glycoprotein antagonist PSC 833 (valspodar). Cancer 2001, 92, 1577-1590.
104. Chico, I.; Kang, M. H.; Bergan, R.; Abraham, J.; Bakke, S.; Meadows, B.; et al. Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833. J. Clin. Oncol. 2001, 19, 832-842.
105. Minami, H.; Ohtsu, T.; Fujii, H.; Igarashi, T.; Itoh, K.; Uchiyama-Kokubu, N.; et al. Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug resistance. Jpn. J. Cancer Res. 2001, 92, 220-230.
106. Wishart, G. C.; Bissett, D.; Paul, J.; Jodrell, D.; Harnett, A.; Habeshaw, T.; et al. Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial. J. Clin. Oncol. 1994, 12, 1771-1777.
107. Solary, E.; Caillot, D.; Chauffert, B.; Casasnovas, R. O.; Dumas, M.; Maynadie, M.; et al. Feasibility of using quinine, a potential multidrug resistance -reversing agent, in combination with mitoxantrone and cytarabine for the treatment of acute leukemia. J. Clin. Oncol. 1992, 10, 1730-1736.
108. Solary, E.; Witz, B.; Caillot, D.; Moreau, P.; Desablens, B.; Cahn, J. Y.; et al. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood 1996, 88, 1198-1205.
109. Miller, T. P.; Chase, E. M.; Dorr, R.; Dalton, W. S.; Lam, K. S.; Salmon, S. E. A phase I/II trial of paclitaxel for non-Hodgkin's lymphoma followed by paclitaxel plus quinine in drug-resistant disease. Anti-Cancer Drugs 1998, 9, 135-140.
110. Solary, E.; Mannone, L.; Moreau, D.; Caillot, D.; Casasnovas, R. O.; Guy, H.; et al. Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes. Leukemia 2000, 14, 2085-2094.
111. Naito, M.; Matsuba, Y.; Sato, S.; Hirata, H.; Tsuruo, T. MS-209, a quinoline-type reversal agent, potentiates antitumor efficacy of docetaxel in multidrug-resistant solid tumor xenograft models. Clin. Cancer Res. 2002, 8, 582-588.
112. Peck, R. A.; Hewett, J.; Harding, M. W.; Wang, Y. M.; Chaturvedi, P. R.; Bhatnagar, A.; et al. Phase I and pharmacokinetic study of the novel MDR1 and MRP1 inhibitor biricodar administered alone and in combination with doxorubicin. J. Clin. Oncol. 2001, 19, 3130-3141.
113. Rowinsky, E. K.; Smith, L.; Wang, Y. M.; Chaturvedi, P.; Villalona, M.; Campbell, E.; et al. Phase I and pharmacokinetic study of paclitaxel in combination with biricodar, a novel agent that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP. J. Clin. Oncol. 1998, 16, 2964-2976.
114. Germann, U. A.; Shlyakhter, D.; Mason, V. S.; Zelle, R. E.; Duffy, J. P. ; Galullo, V.; et al. Cellular and biochemical characterization of VX-710 as a chemosensitizer: reversal of P-glycoprotein-mediated multidrug resistance in vitro. Anti-Cancer Drugs 1997, 8, 125-140.
115. Germann, U. A.; Ford, P. J.; Shlyakhter, D.; Mason, V. S.; Harding, M. W. Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP. Anti-Cancer Drugs 1997, 8, 141-155.
116. Pierre, A.; Dunn, T. A.; Kraus-Berthier, L.; Leonce, S.; Saint-Dizier, D.; Regnier, G.; et al. In vitro and in vivo circumvention of multidrug resistance by Servier 9788, a novel triazinoaminopiperidine derivative. Invest. New Drugs 1992, 10, 137-148.
117. Punt, C. J.; Voest, E. E.; Tueni, E.; Van Oosterom, A. T.; Backx, A.; De Mulder, P. H.; et al. Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer. Br. J. Cancer 1997, 76, 1376-1381.
118. de Bruin, M.; Miyake, K.; Litman, T.; Robey, R.; Bates, S. E. Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett. 1999, 146, 117-126.
119. Sparreboom, A.; Planting, A. S.; Jewell, R. C.; van der Burg, M. E.; van der Gaast, A.; de Bruijn, P.; et al. Clinical pharmacokinetics of doxorubicin in combination with GF120918, a potent inhibitor of MDR1 P-glycoprotein. Anti-Cancer Drugs 1999, 10, 719-728.
120. Kruijtzer, C. M.; Beijnen, J. H.; Rosing, H.; Ten Bokkel, H.; Schot, M.; Jewell, R. C.; et al. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J. Clin. Oncol. 2002, 20, 2943-2950.
121. Malingre, M. M.; Beijnen, J. H.; Rosing, H.; Koopman, F. J.; Jewell, R. C.; Paul, E. M.; et al. Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients. Br. J. Cancer 2001, 84, 42-47.
122. Dantzig, A. H.; Law, K. L.; Cao, J.; Starling, J. J. Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic. Curr. Med. Chem. 2001, 8, 39-50.
123. Shepard, R. L.; Cao, J.; Starling, J. J.; Dantzig, A. H. Modulation of P-glycoprotein but not MRP1- or BRCP-mediated drug resistance by LY335979. Int. J. Cancer 2003, 103, 121-125.
124. Rubin, E. H.; De Alwis, D. P.; Pouliquen, I.; Green, L.; Marder, P.; Lin, Y.; et al. A phase I trial of a potent P-glycoprotein inhibitor, zosuquidar-3HCl trihydrochloride (LY335979), administered orally in combination with doxorubicin in patients with advanced malignancies. Clin. Cancer Res. 2002, 8, 3710-3717.
125. Mistry, P.; Stewart, A. J.; Dangerfield, W.; Okiji, S.; Liddle, C.; Bootle, D.; et al. In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res. 2001, 61, 749-758.
126. Stewart, A.; Steiner, J.; Mellows, G.; Laguda, B.; Norris, D.; Bevan, P. Phase I trial of XR9576 in healthy volunteers demonstrates modulation of P-glycoprotein in CD56+ lymphocytes after oral and intravenous administration. Clin. Cancer Res. 2000, 6, 4186-4191.
127. Mechetner, E. B.; Roninson, I. B. Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 5824-5828.
128. Alahari, S. K.; Dean, N. M.; Fisher, M. H.; Delong, R.; Manoharan, M.; Tivel, K. L.; et al. Inhibition of expression of the multidrug resistance-associated P-glycoprotein of by phosphorothioate and 5′ cholesterol-conjugated phosphorothioate antisense oligonucleotides. Mol. Pharmacol. 1996, 50, 808-819.
129. Labialle, S.; Gayet, L.; Marthinet, E.; Rigal, D.; Baggetto, L. G. Transcriptional regulators of the human multidrug resistance 1 gene: recent views. Biochem. Pharmacol. 2002, 64, 943-948.
130. Thierry, A. R.; Vige, D.; Coughlin, S. S.; Belli, J. A.; Dritschilo, A.; Rahman, A. Modulation of doxorubicin resistance in multidrug-resistant cells by liposomes. FASEB J. 1993, 7, 572-579.
131. Cuvier, C.; Roblot-Treupel, L.; Millot, J. M.; Lizard, G.; Chevillard, S.; Manfait, M.; et al. Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance. Biochem. Pharmacol. 1992, 44, 509-517.
132. Shtil, A. A. P-glycoprotein as a therapeutic target: good news. Leukemia 2002, 16, 2169-2170.
133. Lehne, G.; Sorensen, D. R.; Tjonnfjord, G. E.; Beiske, C.; Hagve, T. A.; Rugstad, H. E.; et al. The cyclosporin PSC 833 increases survival and delays engraftment of human multidrug-resistant leukemia cells in xenotransplanted NOD-SCID mice. Leukemia 2002, 16, 2388-2394.
134. Millward, M. J.; Cantwell, B. M.; Munro, N. C.; Robinson, A.; Corris, P. A.; Harris, A. L. Oral verapamil with chemotherapy for advanced non-small cell lung cancer: a randomised study. Br. J. Cancer 1993, 67, 1031-1035.
135. Philip, P. A.; Joel, S.; Monkman, S. C.; Dolega-Ossowski, E.; Tonkin, K. ; Carmichael, J.; et al. A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide. Br. J. Cancer 1992, 65, 267-270.
136. Budd, G. T.; Bukowski, R. M.; Lichtin, A.; Bauer, L.; Van Kirk, P.; Ganapathi, R. Phase II trial of doxorubicin and trifluoperazine in metastatic breast cancer. Invest. New Drugs 1993, 11, 75-79.
137. Miller, R. L.; Bukowski, R. M.; Budd, G. T.; Purvis, J.; Weick, J. K.; Shepard, K.; et al. Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial. J. Clin. Oncol. 1988, 6, 880-888.
138. Murren, J. R.; Durivage, H. J.; Buzaid, A. C.; Reiss, M.; Flynn, S. D.; Carter, D.; et al. Trifluoperazine as a modulator of multidrug resistance in refractory breast cancer. Cancer Chemother. Pharmacol. 1996, 38, 65-70.
139. List, A. F.; Spier, C.; Greer, J.; Wolff, S.; Hutter, J.; Dorr, R.; et al. Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J. Clin. Oncol. 1993, 11, 1652-1660.
140. Sarris, A. H.; Younes, A.; McLaughlin, P.; Moore, D.; Hagemeister, F.; Swan, F.; et al. Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with relapsed non-Hodgkin's lymphoma. J. Clin. Oncol. 1996, 14, 233-239.
141. Solary, E.; Witz, B.; Caillot, D.; Moreau, P.; Desablens, B.; Cahn, J. Y.; et al. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood 1996, 88, 1198-1205.
142. Berman, E.; McBride, M.; Lin, S.; Menedez-Botet, C.; Tong, W. Phase I trial of high-dose tamoxifen as a modulator of drug resistance in combination with daunorubicin in patients with relapsed or refractory acute leukemia. Leukemia 1995, 9, 1631-1637.
143. Samuels, B. L.; Hollis, D. R.; Rosner, G. L.; Trump, D. L.; Shapiro, C. L.; Vogelzang, N. J.; et al. Modulation of vinblastine resistance in metastatic renal cell carcinoma with cyclosporine A or tamoxifen: a cancer and leukemia group B study. Clin. Cancer Res. 1997, 3, 1977-1984.
144. Trump, D. L.; Smith, D. C.; Ellis, P. G.; Rogers, M. P.; Schold, S. C.; Winer, E. P.; et al. High-dose oral tamoxifen, a potential multidrug-resistance-reversal agent: phase I trial in combination with vinblastine. J. Natl. Cancer Inst. 1992, 84, 1811-1816.
145. Christen, R. D.; McClay, E. F.; Plaxe, S. C.; Yen, S. S.; Kim, S.; Kirmani, S.; et al. Phase I/pharmacokinetic study of high-dose progesterone and doxorubicin. J. Clin. Oncol. 1993, 11, 2417-2426.
146. Isonishi, S.; Kirmani, S.; Kim, S.; Plaxe, S. C.; Braly, P. S.; McClay, E. F.; et al. Phase I and pharmacokinetic trial of intraperitoneal etoposide in combination with the multidrug-resistance-modulating agent dipyridamole. J. Natl. Cancer Inst. 1991, 83, 621-626.
147. Murphy, B. R.; Rynard, S. M.; Pennington, K. L.; Grosh, W.; Loehrer, P. J. A phase II trial of vinblastine plus dipyridamole in advanced renal cell carcinoma. A Hoosier oncology group study. Am. J. Clin. Oncol. 1994, 17, 10-13.
148. Bates, S. E.; Meadows, B.; Goldspiel, B. R.; Denicoff, A.; Le, T. B.; Tucker, E.; et al. A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer. Cancer Chemother. Pharmacol. 1995, 35, 457-463.
149. Linn, S. C.; van Kalken, C. K.; van Tellingen, O.; van der Valk, P.; van Groeningen, C. J.; Kuiper, C. M.; et al. Clinical and pharmacologic study of multidrug resistance reversal with vinblastine and bepridil. J. Clin. Oncol. 1994, 12, 812-819.
150. Ukena, D.; Boewer, C.; Oldenkott, B.; Rathgeb, F.; Wurst, W.; Zech, K.; et al. Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial. Cancer Chemother. Pharmacol. 1995, 36, 160-164.
151. Braybrooke, J. P.; Vallis, K. A.; Houlbrook, S.; Rockett, H.; Ellmen, J. ; Anttila, M.; et al. Evaluation of toremifene for reversal of multidrug resistance in renal cell cancer patients treated with vinblastine. Cancer Chemother. Pharmacol. 2000, 46, 27-34.