ABC transporters and inhibitors: New targets, new agents

Current Opinion in Investigational Drugs

Volumn 3, Issue 11, 2002, Pages 1652-1659

  Leonard, Gregory D ^a   Polgar, Orsolya ^a   Bates, Susan E ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

ABC transporter; Chemosensitizer; Membrane pump; Multidrug resistance; P glycoprotein

Indexed keywords

ABC TRANSPORTER; ANTINEOPLASTIC AGENT; BIRICODAR; CARBOPLATIN; CBT 1; CISPLATIN; CYCLOSPORIN A; CYTARABINE; DAUNORUBICIN; DEXNIGULDIPINE; DEXVERAPAMIL; DOCETAXEL; DOXORUBICIN; ELACRIDAR; ETOPOFOS; ETOPOSIDE; GLYCOPROTEIN P INHIBITOR; GW 120918; IDARUBICIN; IRINOTECAN; LANIQUIDAR; METHOXY ISOBUTYL ISONITRILE TECHNETIUM TC 99M; MITOXANTRONE; NAVELBINE; NSC 77037; OC 144 093; ONT 093; PACLITAXEL; TARIQUIDAR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALSPODAR; VINCRISTINE; ZOSUQUIDAR;

ACUTE LEUKEMIA; AREA UNDER THE CURVE; BREAST CANCER; CANCER RESISTANCE; CLINICAL TRIAL; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DETERMINATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG INDICATION; DRUG POTENTIATION; DRUG TARGETING; DRUG TOXICITY; HUMAN; IMAGING SYSTEM; LEUKEMIA; MALIGNANT NEOPLASTIC DISEASE; MULTIDRUG RESISTANCE; NONHUMAN; OVARY CANCER; PROTEIN EXPRESSION; REVIEW; SARCOMA; SIDE EFFECT; TREATMENT OUTCOME; TUMOR;

ANIMALS; ANTINEOPLASTIC AGENTS; ATP-BINDING CASSETTE TRANSPORTERS; CLINICAL TRIALS; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, MULTIPLE; HUMANS; P-GLYCOPROTEIN;

EID: 0036881871     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (80)

1. Dean M, Hamon Y, Chimini G: The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res (2001) 42(7):1007-1017. Overview of the seven ABC transporter subfamilies, and related diseases with a special emphasis on the ABCA and and ABCG families.
2. Gottesman MM, Fojo T, Bates SE: Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat Rev Cancer (2002) 2:48-56. Overview of ABC transporters linked to drug resistance, including overvie of clinical drug resistance reversal strategies.
3. Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM: Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol (1999) 39:361-398.
4. Hipfner DR, Deeley RG, Cole SP: Structural, mechanistic and clinical aspects of MRP1. Biochim Biophys Acta (1999) 1461(2):359-376.
5. Borst P, Evers R, Kool M, Wijnholds J: A family of drug transporters: The multidrug resistance-associated proteins. J Natl Cancer Inst (2002) 92(16):1295-1302.
6. Allen JD, Schinkel AH: Multidrug resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2). Mol Caner Ther (2002) 1(6):427-434. Excellent overview of ABCG2.
7. Honjo Y, Hrycyna CA, Yan QW, Medina-Perez WY, Robey RW, Van De Laar A, Litman T, Dean M, Bates SE: Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res (2001) 61(18):6635-6639.
8. Allen JD, Jackson SC, Schinkel AH: A mutation hot spot in the Bcrp1 (Abcg2) multidrug transporter in mouse cell lines selected for doxorubicin resistance. Cancer Res (2002) 62(8):2294-2299.
9. Beck WT, Grogan TM, Willman CL, Cordon-Cardo C, Parham DM, Kuttesch JF, Andreeff M, Bates SE, Berard CW, Boyett JM, Brophy NA, et al: Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: Consensus recommendations. Cancer Res (1996) 56(13):3010-3020.
10. Bates SE: Solving the problems of multidrug resistance: ABC transporters in clinical oncology. In ABC Proteins: From Bacteria to Man. Holland IB, Cole SPC, Kuchler K, Higgins CF (Eds), Elsevier Science, London, UK (2002):359-391.
11. Nooter K, Westerman AM, Flens MJ, Zaman GJ, Scheper RJ, Van Wingerden KE, Burger H, Oostrum R, Boersma T, Sonneveld P et al: Expression of the multidrug resistance-associated protein (MRP) gene in human cancers. Clin Cancer Res (1995) 1(11):1301-1310.
12. Ross DD, Karp JE, Chen TT, Doyle LA: Expression of breast cancer resistance protein in blast cells from patients with acute leukemia. Blood (2000) 96(1):365-368.
13. Steinbach D, Sell W, Voigt A, Hermann J, Zintl F, Sauerbrey A: BCRP gene expression is associated with a poor response to remission inductdion therapy in childhood acute myeloid leukemia. Leukemia (2002) 16(8):1443-1447.
14. Sargent JM, Williamson CJ, Maliepaard M, Elgie AW, Scheper RJ, Taylor CG: Breast cancer resistance protein expression and resistance to daunorubicin in blast cells from patients with acute myeloid leukaemia. Br J Haematol (2001) 115(2):257-262.
15. Van Der Kolk DM, Vellenga E, Scheffer GL, Muller M, Bates SE, Scheper RJ, De Vries EG: Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia. Blood (2002) 99(10):3763-3770.
16. Van Der Heuven-Eibrink MM, Wiemer EA, Prins A, Meijerink JP, Vossebeld PJ, Van Der Holt B, Pieters R, Sonneveld P: Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML). Leukemia (2002) 16(5):833-839.
17. Diestra JE, Scheffer GL, Catala II, Maliepaard M, Schellens JH, Scheper RJ, Gema-Lluch JR, Izquierdo MA: Frequent expression of the multidrug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material. J Pathol (2002) 198(2):213-219. First extensive study of ABCG2 expression in human tumors by immunohistochemistry.
18. Kanzaki A, Toi M, Nakayama K, Bando H, Mutoh M, Uchida T, Fukumoto M, Takebayashi Y: Expression of multidrug resistance-related transporters in human breast carcinoma. Jpn J Cancer Res (2001) 92(4):452-458.
19. Faneyte IF, Kristel PM, Maliepaard M, Scheffer GL, Scheper RJ, Schellens JH, Van De Vijver MJ: Expression of the breast cancer resistance protein in breast cancer. Clin Cancer Res (2002) 8(4):1068-1074.
20. List AF, Spier CS, Grogan TM, Johnson C, Roe DJ, Greer JP, Wolff SN, Broxterman HJ, Scheffer GL, Scheper RJ, Dalton WS: Overexpresson of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. Blood (1996) 87(6):2464-2469.
21. Tsimberidou AM, Paterakis G, Androutsos G, Anagnostopoulos N, Galanopoulos A, Kalmantis T, Meletis J, Rombos Y, Sagriotis A, Symeonidis A, Tiniakou M et al: Evaluation of the clinical relevance of the expression and function of P-glycoprotein, multidrug resistance protein and lung resistance protein in patients with primary acute myelogenous leukemia. Leuk Res (2002) 26(2):143-154.
22. Legrand O, Simonin G, Beauchamp-Nicoud A, Zittoun R, Marie JP: Simultaneous activity of MRP1 and Pgp is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia. Blood (1999) 94(3):1046-1056.
23. Van Der Kolk DM, De Vries EG, Van Putten WJ, Verdonck LF, Ossenkoppele GJ, Verhoef GE, Vellenga E: P-glycoprotein and multidrug resistance protein activities in relation to treatment outcome in acute myeloid leukemia. Clin Cancer Res (2000) 6(8):3205-3214. Study showing that P-gp detection was of prognostic value in 104 patients with AML, as studied by flow cytometry.
24. Tsuruo T, Iida H, Tsukagoshi S, Sakura Y: Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res (1981) 41(5):1967-1972.
25. Ozols RF, Cunnion RE, Klecker RW, Hamilton TC, Ostchega Y, Parrillo JE, Young RC: Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J Clin Oncol (1987) 5(4):641-647.
26. Abraham J, Bakke S, Rutt A, Meadows B, Merino M, Alexander R, Schrump D, Bartlett D, Choyke P, Robey R, Hung E et al: A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: Continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist. Cancer (2002) 94(9):2333-2343.
27. Dalton WS, Crowley JJ, Salmon SS, Grogan TM, Laufman LR, Weiss GR, Bonnett JD: 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(3):815-820.
28. Wishart GC, Bissett D, Paul J, Jodrell D, Harnett A, Habeshaw T, Kerr DJ, Macham MA, Soukop M, Leonard RCF, Knepil J 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(9):1771-1777.
29. Baer MR, George SL, Dodge RK, O'Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD et al: Phase III 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(4):1224-1232. First randomized trial with valspodar to be reported. Early deaths required closure of the valspodar-containing arm, but subset analysis suggested benefit in patients with P-gp expression on the surface of their leukemia cells.
30. Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D 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(4):1198-1205.
31. Millward MJ, Cantwell BM, Munro NC, Robinson A, Corris PA, Harris AL: Oral verapamil with chemotherapy for advanced non-small cell lung cancer: A randomised study. Br J Cancer (1993) 67(5):1031-1035.
32. Milroy R: A randomised clinical study of verapamil in addition to combination chemotherapy in small cell lung cancer. West of Scotland Lung Cancer Research Group, and the Aberdeen Oncology Group. Br J Cancer (1993) 68(4):813-818.
33. List AF, Kopecky KJ, Willman CL, Head DR, Persons DL, Slovak ML, Dorr R, Karanes C, Hynes HE, Doroshow JH, Shurafa M 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(12):3212-3220. Randomized trial showing survival advantage in AML patients receiving cyclosporin in combination with daunorubicin and Ara-C. The greatest benefit was observed in the group of patients with P-gp expression on their leukemic cells.
34. Belpomme D, Gauthier S, Pujade-Lauraine E, Facchini T, Goudier MJ, Krakowski I, Netter-Pinon G, Frenay M, Gousset C, Marie FN, Benmiloud M et al: Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma. Ann Oncol (2000) 11(11):1471-1476.
35. List AF, Spier C, Greer J, Wolff S, Hutter J, Dorr R, Salmon S, Futscher B, Baier M, Dalton W: Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J Clin Oncol (1993) 11(9):1652-1660.
36. Kivisto KT, Kroemer HK, Eichelbaum M: The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: Implications for drug interactions. Br J Clin Pharmacol (1995) 40(6):523-530.
37. Wacher VJ, Wu CY, Benet LZ: Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: Implications for drug delivery and activity in cancer chemotherapy. Mol Carcinog (1995) 13(3):129-134.
38. Fracasso PM, Westerveldt P, Fears CA, Rosen DM, Zuhowski EG, Cazenave LA, Litchman M, Egorin MJ: Phase I study of paclitaxel in combination with a multidrug resistance modulator, PSC 833 (Valspodar), in refractory malignancies. J Clin Oncol (2000) 18(5):1124-1134.
39. Chico I, Kang MH, Bergan R, Abraham J, Bakke S, Meadows B, Rutt A, Robey R, Choyke P, Merino M, Goldspiel B et al: Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833. J Clin Oncol (2001) 19(3):832-842.
40. Dorr R, Karanes C, Spier C, Grogan T, Greer J, Moore J, Weinberger B, Schiller G, Pearce T, Litchman M, Dalton W et al: Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia. J Clin Oncol (2001) 19(6):1589-1599. Study reporting interpatient variability of pharmacokinetic interaction due to PSC-833, which has been confirmed by other research groups.
41. Joly F, Joly F, Mangioni C, Nicoletto M, Manikhas GM, Walker J, Mietlowski W, Jones G, Wysowskyj H, Dugan M. A phase III study of PSC 833 in combination with paclitaxel and carboplatin (PC-PSC) versus paclitaxel and carboplatin (PC) alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary cancer of the peritoneum. Proc Am Soc Clin Oncol (2002) 21(1):Abs 806.
42. Germann UA, Ford PJ, Shlyakhter D, Mason VS, Harding MW: 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. Anticancer Drugs (1997) 8(2):141-155.
43. Toppmeyer D, Seidman AD, Pollak M, Russell C, Tkaczuk K, Verma S, Overmoyer B, Garg V, Ette E, Harding MW, Demetri GD: Safety and efficacy of the multidrug resistance inhibitor Incel (biricodar; VX-710) in combination with paclitaxel for advanced breast cancer refractory to paclitaxel. Clin Cancer Res (2002) 8(3):670-678.
44. Seiden MV, Swenerton KD, Matulonis U, Campos S, Rose P, Batist G, Ette E, Garg V, Fuller A, Harding MW, Charpentier D: A phase II study of the MDR inhibitor biricodar (INCEL, VX-710) and paclitaxel in women with advanced ovarian cancer refractory to paclitaxel therapy. Gynecol Oncol (2002) 86(3):302-310.
45. Bramwell VH, Morris D, Ernst DS, Hings I, Blackstein M, Venner PM, Ette EI, Harding MW, Waxman A, Demetri GD: Safety and efficacy of the multidrug-resistance inhibitor biricodar (VX-710) with concurrent doxorubicin in patients with anthracycline-resistant advanced soft tissue sarcoma. Clin Cancer Res (2002) 8(2):383-393.
46. Robey R, Bakke S, Stein W, Meadows B, Litman T, Patil S, Smith T, Fojo T, Bates S: Efflux of rhodamine from CD56+ cells as a surrogate marker for reversal P-glycoprotein-mediated drug efflux by PSC 833. Blood (1999) 93(1):306-314.
47. Peck RA, Hewett J, Harding MW, Wang YM, Chaturvedi PR, Bhatnagar A, Ziessman H, Atkins F, Hawkins MJ: 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(12):3130-3141.
48. Chen CC, Meadows B, Regis J, Kalafsky G, Fojo T, Carrasquillo JA, Bates SE: Detection of in vivo p-glycoprotein inhibition by PSC 833 using Tc-99m sestamibi. Clin Cancer Res (1997) 3(4):545-552.
49. 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors following the administration of the P-glycoprotein inhibitor, XR9576 (tariquidar). Clin Cancer Res (2002) in press. Demonstration that the third generation agent tariquidar convincingly increases P-gp expression in normal tissues and tumors.
50. Mistry P, Stewart AJ, Dangerfield W, Okiji S, Liddle C, Bootle D, Plumb JA, Templeton D, Charlton P: In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res (2001) 61(2):749-758.
51. Newman MJ, Rodarte JC, Benbatoul KD, Romano SJ, Zhang C, Krane S, Moran EJ, Uyeda RT, Dixon R, Guns ES, Mayer LD: Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance. Cancer Res (2000) 60(11):2964-2972.
52. Van Zuylen L, Sparreboom A, Van Der Gaast A, Van Der Burg ME, Van Beurden V, Bol CJ, Woestenborghs R, Palmer PA, Verweij J: The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel. Clin Cancer Res (2000) 6(4):1365-1371.
53. Starling JJ, Shepard RL, Cao J, Law KL, Norman BH, Kroin JS, Ehlhardt WJ, Baughman TM, Winter MA, Bell MG, Shih C et al: Pharmacological characterization of LY335979: A potent cyclopropyldibenzosuberane modulator of P-glycoprotein. Adv Enzyme Regul (1997) 37:335-347.
54. Sparreboom A, Planting AS, Jewell RC, Van Der Burg ME, Van Der Gaast A, De Bruijn P, Loos WJ, Nooter K, Chandler LH, Paul EM, Wissel PS et al: Clinical pharmacokinetics of doxorubicin in combination with GF120918, a potent inhibitor of MDR1 P-glycoprotein. Anticancer Drugs (1999) 10(8):719-728.
55. Gekeler V, Ise W, Sanders KH, Ulrich WR, Beck J: The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance. Biochem Biophys Res Commun (1995) 208(1):345-352.
56. Chen ZS, Furukawa T, Sumizawa T, Ono K, Ueda K, Seto K, Akiyama SI: ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol (1999) 55(5):921-928.
57. De Bruin M, Miyake K, Litman T, Robey R, Bates SE: Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett (1999) 146(2):117-126.
58. Allen JD, Van Loevezijn A, Lakhai JM, Van Der Valk M, Van Tellingen O, Reid G, Schellens JHM, Koomen G-J, Schinkel AH: Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther (2002) 1(6):417-425. A study detailing the development of analogs of fumitremorgin C developed to overcome ABCG2 mediated drug efflux.
59. Han K, Kahng J, Kim M, Lim J, Kim Y, Cho B, Kim HK, Min WS, Kim CC, Lee KY, Kim BK et al: Expression of functional markers in acute nonlymphoblastic leukemia. Acta Haematol (2000) 104(4):174-180.
60. Nooter K, Burger H, Stoter G: Multidrug resistance-associated protein (MRP) in haematological malignancies. Leuk Lymphoma (1996) 20(5-6):381-387.
61. Chauncey TR, Rankin C, Anderson JE, Chen I, Kopecky KJ, Godwin JE, Kalaycio ME, Moore DF, Shurafa MS, Petersdorf SH, Kraut EH 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(7):567-574.
62. Zhou DC, Zittoun R, Marie JP: Expression of multidrug resistance-association protein (MRP) and multidrug resistance (MDR1) genes in acute myeloid leukemia. Leukemia (1995) 9(10):1661-1666.
63. Filipits M, Suchomel RW, Zochbauer S, Brunner R, Lechner K, Pirker R: Multidrug resistance-associated protein in acute myeloid leukemia: No impact on treatment outcome. Clin Cancer Res (1997) 3(8):1419-1425.
64. Filipits M, Pohl G, Stranzl T, Suchomel RW, Scheper RJ, Jager U, Geissler K, Lechner K, Pirker R: Expression of the lung resistance protein predicts poor outcome in de novo acute myeloid leukemia. Blood (1998) 91(5):1508-1513.
65. Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS, Head DR, Weick J, Grever MR, Appelbaum FR, Willman CL: 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(3):1086-1099. Study including 352 patients showing the prognostic value of P-gp, based on immunohistochemical and functional data.
66. Michieli M, Damiani D, Ermacora A, Masolini P, Raspadori D, Visani G, Scheper RJ, Baccarani M: P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias: Biological and clinical implications. Br J Haematol (1999) 104(2):328-335.
67. Boote DJ, Dennis IF, Twentyman PR, Osborne RJ, Laburte C, Hensel S, Smyth JF, Brampton MH, Bleehen NM: Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J Clin Oncol (1996) 14(2):610-618.
68. Giaccone G, Linn SC, Welink J, Catimel G, Stieltjes H, Van Der Vijgh WJ, Eeltink C, Vermorken JB, Pinedo HM: 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(11):2005-2015.
69. Minami H, Ohtsu T, Fujii H, Igarashi T, Itoh K, Uchiyama-Kokubu N, Aizawa T, Watanabe T, Uda Y, Tanigawara Y, Sasaki Y: Phase I study of intravenous PSC-833 and doxorubicin: Reversal of multidrug resistance. Jpn J Cancer Res (2001) 92(2):220-230.
70. Bates S, Kang M, Meadows B, Bakke S, Choyke P, Merino M, Goldspiel B, Chico I, Smith T, Chen C, Robey R et al: A Phase I study of infusional vinblastine in combination with the P-glycoprotein antagonist PSC 833 (valspodar). Cancer (2001) 92(6):1577-1590.
71. Sonneveld P, Marie J-P, Huisman C, Vekhoff A, Schoester M, Faussat AM, Van Kapel J, Groenewegen A, Charnick S, Zittoun R, Lowenberg B: Reversal of multidrug resistance by SDZ PSC 833, combined with VAD (vincristine, doxorubicin, dexamethasone) in refractory multiple myeloma. A phase I study. Leukemia (1996) 10(11):1741-1750.
72. Patnaik A, Warner E, Michael M, Egorin MJ, Moore MJ, Siu LL, Fracasso PM, Rivkin S, Kerr I, Litchman M, Oza AM: Phase I dose-finding and pharmacokinetic study of paclitaxel and carboplatin with oral valspodar in patients with advanced solid tumors. J Clin Oncol (2000) 18(21):3677-3689.
73. Advani R, Fisher GA, Lum BL, Hausdorff J, Halsey J, Litchman M, Sikic BI: A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance. Clin Cancer Res (2001) 7(5):1221-1229.
74. Fracasso PM, Brady MF, Moore DH, Walker JL, Rose PG, Letvak L, Grogan TM, McGuire WP: Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: A gynecologic oncology group study. J Clin Oncol (2001) 19(12):2975-2982.
75. Baekelandt M, Lehne G, Trope CG, Szanto I, Pfeiffer P, Gustavsson B, Kristensen GB: Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer. J Clin Oncol (2001) 19(12):2983-2993.
76. Kornblau SM, Estey E, Madden T, Tran HT, Zhao S, Consoli U, Snell V, Sanchez-Williams G, Kantarjian H, Keating M, Newman RA, et al: Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia. J Clin Oncol (1997) 15(5):1796-1802.
77. Advani R, Saba HI, Tallman MS, Rowe JM, Wiernik PH, Ramek J, Dugan K, Lum B, Villena J, Davis E, Paietta E et al: Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood (1999) 93(3):787-795.
78. Lee EJ, George SL, Caligiuri M, Szatrowski TP, Powell BL, Lemke S, Dodge RK, Smith R, Baer M, Schiffer CA: 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(9):2831-2839.
79. Visani G, Milligan D, Leoni F, Chang J, Kelsey S, Marcus R, Powles R, Schey S, Covelli A, Isidori A, Litchman M 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(5):764-771.
80. Rowinsky EK, Smith L, Wang YM, Chaturvedi P, Villalona M, Campbell E, Aylesworth C, Eckhardt SG, Hammond L, Kraynak M, Drengler R et al: Phase I and pharmacokinetic study of paclitaxel combination with biricolar, a novel agent that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP. J Clin Oncol (1998) 16(9):2964-2976.