Chapter 12
Multidrug Resistance Reversal in Solid Tumors
Tatiana Bogush, Jacques Robert,
Jacques Robert
Institut Bergonié, Université Victor Segalen, Bordeaux, France
Search for more papers by this authorTatiana Bogush, Jacques Robert,
Jacques Robert
Institut Bergonié, Université Victor Segalen, Bordeaux, France
Search for more papers by this authorBook Editor(s):Ahcène Boumendjel, Jean Boutonnat,
Jacques Robert,
Jean Boutonnat
Institut Jean Roget, Université Joseph Fourier, Grenoble, France
Hôpital Michallon de Grenoble, Grenoble, France
Search for more papers by this authorJacques Robert
Institut Bergonié, Université Victor Segalen, Bordeaux, France
Search for more papers by this authorFirst published: 15 June 2009
Series Editor(s): Binghe Wang,
Binghe Wang
Search for more papers by this authorSummary
This chapter contains sections titled:
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Introduction
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Clinical trials aimed at MDR reversal in solid tumors
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MDR reversal in solid tumors: The reasons for a failure
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Conclusions
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References
REFERENCES
- Tsuruo T, Iida H, Tsukagoshi S, and Sakurai Y. 1981. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41: 1967–1972.
- Ford JM and Hait WN. 1990. Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol Rev 42: 155–199.
- Robert J and Jarry C. 2003. Multidrug resistance reversal agents. J Med Chem 46: 4805–4817.
- Modok S, Mellor HR, and Callaghan R. 2006. Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. Curr Opin Pharmacol 6: 350–354.
- Nobili S, Landini I, Giglioni B, and Mini E. 2006. Pharmacological strategies for overcoming multidrug resistance. Curr Drug Targets 7: 861–879.
- Ozols RF, Cunnion RE, Klecker RWJ, Hamilton TC, Ostchega Y, Parrillo JE et al. 1987. Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J Clin Oncol 5: 641–647.
- Demicheli R, Jirillo A, Bonciarelli G, Lonardi F, Balli, M, and Bandello A. 1989. 4′-Epidoxorubicin plus verapamil in anthracycline refractory cancer patients. Tumori 75: 245–247.
- Langenbuch T, Mross K, Jonat W, and Hossfeld DK. 1990. A phase II study of intensive-dose epirubicin/verapamil as induction therapy followed by intensivedose ifosfamide for advanced breast cancer. Cancer Chemother Pharmacol 26: S93–S96.
- Mross K, Bohn C, Edler L, Jonat W, Queisser W, Heidemann E et al. 1993. Randomized phase II study of single-agent epirubicin/verapamil in patients with advanced metastatic breast cancer. Ann Oncol 4: 45–50.
- Millward MJ, Cantwell BM, Munro NC, Robinson A, Corris PA, and Harris AL. 1993. Oral verapamil with chemotherapy for advanced non-small cell lung cancer: A randomised study. Br J Cancer 67: 1031–1035.
- Cairo MS, Siegel S, Anas N, and Sender L. 1989. Clinical trial of continuous infusion verapamil, bolus vinblastine, and continuous infusion VP-16 in drug-resistant pediatric tumors. Cancer Res 49: 1063–1066.
- Belpomme D, Gauthier S, Pujade-Lauraine E, Facchini T, Goudier MJ, Krakowski I et al. 2000. Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma. Ann Oncol 11: 1471–1476.
- Gruber A, Peterson C, and Reizenstein P. 1988. D-verapamil and Lverapamil are equally effective in increasing vincristine accumulation in leukemic cells in vitro. Int J Cancer 41: 224–226.
- Bissett D, Kerr DJ, Cassidy J, Meredith P, Traugott U, and Kaye SB. 1991. Phase I and pharmacokinetic study of D-verapamil and doxorubicin. Br J Cancer 64: 1168–1171.
- Lehnert M, Mross K, Schueller J, Thuerlimann B, Kroeger N, and Kupper H. 1998. Phase II trial of dexverapamil and epirubicin in patients with non-responsive metastatic breast cancer. Br J Cancer 77: 1155–1163.
- Warner E, Hedley D, Andrulis I, Myers R, Trudeau M, Warr D et al. 1998. Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen. Clin Cancer Res 4: 1451–1457.
- Scheithauer W, Kornek G, Kastner J, Raderer M, Locker G, Depisch D et al. 1993. Phase II study of D-verapamil and doxorubicin in patients with metastatic colorectal cancer. Eur J Cancer 29A: 2337–2338.
- Motzer RJ, Lyn P, Fischer P, Lianes P, Ngo RL, Cordon-Cardo C et al. 1995. Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma. J Clin Oncol 13: 1958–1965.
- Verweij J, Herweijer H, Oosterom R, van der Burg ME, Planting AS, Seynaeve C et al. 1991. 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 64: 361–364.
- Rodenburg CJ, Nooter K, Herweijer H, Seynaeve C, Oosterom R, Stoter G et al. 1991. Phase II study of combining vinblastine and cyclosporin-A to circumvent multidrug resistance in renal cell cancer. Ann Oncol 2: 305–306.
- Twentyman PR and Bleehen NM. 1991. Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin. Eur J Cancer 27: 1639–1642.
- Fracasso PM, Westervelt P, Fears CL, Rosen DM, Zuhowski EG, Cazenave LA et al. 2000. Phase I study of paclitaxel in combination with a multidrug resistance modulator, PSC 833 (Valspodar), in refractory malignancies. J Clin Oncol 18: 1124–1134.
- Patnaik A, Warner E, Michael M, Egorin MJ, Moore MJ, Siu LL et al. 2000. Phase I dose-finding and pharmacokinetic study of paclitaxel and carboplatin with oral valspodar in patients with advanced solid tumors. J Clin Oncol 18: 3677–3689.
- Chico I, Kang MH, Bergan R, Abraham J, Bakke S, Meadows B et al. 2001. Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833. J Clin Oncol 19: 832–842.
-
Bates S, Kang M, Meadows B, Bakke S, Choyke P, Merino M et al. 2001. A Phase I study of infusional vinblastine in combination with the P-glycoprotein antagonist PSC 833 (valspodar). Cancer 92: 1577–1590.
10.1002/1097-0142(20010915)92:6<1577::AID-CNCR1484>3.0.CO;2-H CAS PubMed Web of Science® Google Scholar
- Advani R, Fisher GA, Lum BL, Hausdorff J, Halsey J, Litchman M, and Sikic BI. 2001. A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance. Clin Cancer Res 7: 1221–1229.
- Carlson RW, O'Neill AM, Goldstein LJ, Sikic BI, Abramson N, Stewart JA et al. 2006. A pilot phase II trial of valspodar modulation of multidrug resistance to paclitaxel in the treatment of metastatic carcinoma of the breast (E1195): A trial of the Eastern Cooperative Oncology Group. Cancer Invest 24: 677–681.
- Bates SE, Bakke S, Kang M, Robey RW, Zhai S, Thambi P et al. 2004. A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma. Clin Cancer Res 10: 4724–4733.
- Fracasso PM, Brady MF, Moore DH, Walker JL, Rose PG, Letvak L et al. 2001. Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: A gynecologic oncology group study. J Clin Oncol 19: 2975–2982.
- Baekelandt M, Lehne G, Trope CG, Szanto I, Pfeiffer P, Gustavssson B et al. 2001. Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer. J Clin Oncol 19: 2983–2993.
- Lhommé C, Joly F, Walker JL, Lissoni AA, Nicoletto MO, Manikhas GM et al. 2008. Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol 26: 2674–2682.
- Wishart GC, Bissett D, Paul J, Jodrell D, Harnett A, Habeshaw T et al. 1994. Quinidine as a resistance modulator of epirubicin in advanced breast cancer: Mature results of a placebo-controlled randomized trial. J Clin Oncol 12: 1771–1777.
- Diéras V, Bonneterre J, Laurence V, Degardin M, Pierga JY, Bonneterre ME et al. 2005. Phase I combining a P-glycoprotein inhibitor, MS209, in combination with docetaxel in patients with advanced malignancies. Clin Cancer Res 11: 6256–6260.
- Saeki T, Nomizu T, Toi M, Ito Y, Noguchi S, Kobayashi T et al. 2007. Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer. J Clin Oncol 25: 411–417.
- Wang RB, Kuo CL, Lien LL, and Lien EJ. 2003. Structure-activity relationship: Analyses of P-glycoprotein substrates and inhibitors. J Clin Pharm Ther 28: 203–228.
- Wiese M and Pajeva IK. 2001. Structure-activity relationships of multidrug resistance reversers. Curr Med Chem 8: 685–713.
- Rowinsky EK, Smith L, Wang YM, Chaturvedi P, Villalona M, Campbell E et al. 1998. 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 16: 2964–2976.
- Peck RA, Hewett J, Harding MW, Wang YM, Chaturvedi PR, Bhatnagar A et al. 2001. Phase I and pharmacokinetic study of the novel MDR1 and MRP1 inhibitor biricodar administered alone and in combination with doxorubicin. J Clin Oncol 19: 3130–3141.
- Bramwell VH, Morris D, Ernst DS, Hings I, Blackstein M, Venner PM et al. 2002. 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 8: 383–393.
- Toppmeyer D, Seidman AD, Pollak M, Russell C, Tkaczuk K, Verma S et al. 2002. 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 8: 670–678.
- Seiden MV, Swenerton KD, Matulonis U, Campos S, Rose P, Batist G et al. 2002. 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 86: 302–310.
- Rago RP, Einstein A Jr., Lush R, Beer TM, Ko YJ, Henner WD et al. 2003. Safety and efficacy of the MDR inhibitor Incel (biricodar, VX-710) in combination with mitoxantrone and prednisone in hormone-refractory prostate cancer. Cancer Chemother Pharmacol 51: 297–305.
- Gandhi L, Harding MW, Neubauer M, Langer CJ, Moore M, Ross HJ et al. 2007. A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. Cancer 109: 924–932.
- Sparreboom A, Planting AS, Jewell RC, van der Burg ME, van der Gaast A, de Bruijn P et al. 1999. Clinical pharmacokinetics of doxorubicin in combination with GF120918, a potent inhibitor of MDR1 P-glycoprotein. Anti-cancer Drugs 10: 719–728.
- Planting AS, Sonneveld P, van der Gaast A, Sparreboom A, van der Burg ME, Luyten GP et al. 2005. A phase I and pharmacologic study of the MDR converter GF120918 in combination with doxorubicin in patients with advanced solid tumors. Cancer Chemother Pharmacol 55: 91–99.
- Kruijtzer CM, Beijnen JH, Rosing H, Ten Bokkel H, Schot M, Jewell RC et al. 2002. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 20: 2943–2950.
- Kuppens IE, Witteveen EO, Jewell RC, Radema SA, Paul EM, Mangum SG et al. 2007. A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (GF120918) and oral topotecan in cancer patients. Clin Cancer Res 13: 3276–3285.
- Malingre MM, Beijnen JH, Rosing H, Koopman FJ, Jewell RC, Paul EM et al. 2001. Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients. Br J Cancer 84: 42–47.
- Rubin EH, De Alwis DP, Pouliquen I, Green L, Marder P, Lin, Y et al. 2002. A phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered orally in combination with doxorubicin in patients with advanced malignancies. Clin Cancer Res 8: 3710–3717.
- Sandler A, Gordon M, De Alwis DP, Pouliquen I, Green L, Marder P et al. 2004. A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxorubicin in patients with advanced malignancy. Clin Cancer Res 10: 3265–3272.
- Fracasso PM, Goldstein LJ, de Alwis DP, Rader JS, Arquette MA, Goodner SA et al. 2004. Phase I study of docetaxel in combination with the P-glycoprotein inhibitor, zosuquidar, in resistant malignancies. Clin Cancer Res 10: 7220–7228.
- Lê LH, Moore MJ, Siu LL, Oza AM, MacLean M, Fisher B et al. 2005. Phase I study of the multidrug resistance inhibitor zosuquidar administered in combination with vinorelbine in patients with advanced solid tumours. Cancer Chemother Pharmacol 56: 154–160.
- Stewart A, Steiner J, Mellows G, Laguda B, Norris D, and Bevan P. 2000. Phase I trial of XR9576 in healthy volunteers demonstrates modulation of P-glycoprotein in CD56+ lymphocytes after oral and intravenous administration. Clin Cancer Res 6: 4186–4191.
- Agrawal M, Abraham J, Balis FM, Edgerly M, Stein WD, Bates SE et al. 2003. Increased 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576. Clin Cancer Res 9: 650–656.
- Pusztai L, Wagner P, Ibrahim N, Rivera E, Theriault R, Booser D et al. 2005. Phase II study of tariquidar, a selective P-glycoprotein inhibitor, in patients with chemotherapy-resistant, advanced breast carcinoma. Cancer 104: 682–691.
- Mechetner EB and Roninson IB. 1992. Efficient inhibition of Pglycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc Natl Acad Sci U S A 89: 5824–5828.
- Alahari SK, Dean NM, Fisher MH, Delong R, Manoharan M, Tivel KL et al. 1996. Inhibition of expression of the multidrug resistance-associated P-glycoprotein of by phosphorothioate and 5′ cholesterol-conjugated phosphorothioate antisense oligonucleotides. Mol Pharmacol 50: 808–819.
- Labialle S, Gayet L, Marthinet E, Rigal D, and Baggetto LG. 2002. Transcriptional regulators of the human multidrug resistance 1 gene: Recent views. Biochem Pharmacol 64: 943–948.
- Matsui Y, Kobayashi N, Nishikawa M, and Takakura Y. 2005. Sequence-specific suppression of mdr1a/1b expression in mice via RNA interference. Pharm Res 22: 2091–2098.
- Thierry AR, Vige D, Coughlin SS, Belli JA, Dritschilo A, and Rahman A. 1993. Modulation of doxorubicin resistance in multidrug-resistant cells by liposomes. FASEB J 7: 572–579.
- Bennis S, Chapey C, Couvreur P, and Robert J. 1994. Enhanced cytotoxicity of doxorubicin encapsulated in polyisohexylcyanoacrylate nanospheres against multidrug-resistant tumour cells in culture. Eur J Cancer 30A: 89–93.
- Ludwig JA, Szakács G, Martin SE, Chu BF, Cardarelli C, Sauna ZE et al. 2006. Selective toxicity of NSC73306 in MDR1-positive cells as a new strategy to circumvent multidrug resistance in cancer. Cancer Res 66: 4808–4815.
- Fanciulli M, Bruno T, Giovannelli A, Gentile FP, Di Padova M, Rubiu O et al. 2000. Energy metabolism of human LoVo colon carcinoma cells: Correlation to drug resistance and influence of lonidamine. Clin Cancer Res 6: 1590–1597.
- Lopez M, Vici P, Di Lauro L, Paoletti G, Gionfra T, Conti F et al. 1995. Intrapatient comparison of single-agent epirubicin with or without lonidamine in metastatic breast cancer. Eur J Cancer 31A: 1611–1614.
-
Ianniello GP, De Cataldis G, Comella P, Scarpati MD, Maiorino A, Brancaccio L et al. 1996. Cisplatin, epirubicin, and vindesine with or without lonidamine in the treatment of inoperable nonsmall cell lung carcinoma: A multicenter randomized clinical trial. Cancer 78: 63–69.
10.1002/(SICI)1097-0142(19960701)78:1<63::AID-CNCR11>3.0.CO;2-5 CAS PubMed Web of Science® Google Scholar
- Di Cosimo S, Ferretti G, Papaldo P, Carlini P, Fabi A, and Cognetti F. 2003. Lonidamine: Efficacy and safety in clinical trials for the treatment of solid tumors. Drugs Today 39: 157–174.
- van de Vrie W, Marquet RL, Stoter G, De Bruijn EA, and Eggermont AM. 1998. In vivo model systems in P-glycoprotein-mediated multidrug resistance. Crit Rev Clin Lab Sci 35: 1–57.
- Galski H, Sullivan M, Willingham MC, Chin KV, Gottesman MM, Pastan I et al. 1989. Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: Resistance to daunomycin-induced leukopenia. Mol Cell Biol 9: 4357–4363.
- Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L et al. 1994. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77: 491–502.