A phase II study of the MDR inhibitor biricodar (INCEL, VX-710) and paclitaxel in women with advanced ovarian cancer refractory to paclitaxel therapy

Gynecologic Oncology

Volumn 86, Issue 3, 2002, Pages 302-310

  Seiden, Michael V ^a   Swenerton, Kenneth D ^b   Matulonis, Ursula ^c   Campos, Susan ^c   Rose, Peter ^d   Batist, Gerald ^e   Ette, Ene ^f   Garg, Varun ^f   Fuller, Arlan ^a   Harding, Matthew W ^f   Charpentier, Danielle ^g  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b BRITISH COLUMBIA CANCER AGENCY   (Canada)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^e MCGILL UNIVERSITY   (Canada)

^f VERTEX PHARMACEUTICALS   (United States)

^g CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANASTROZOLE; ASTEMIZOLE; BIRICODAR; CIMETIDINE; CYCLOSPORIN; DEXAMETHASONE; DIPHENHYDRAMINE; ETHINYLESTRADIOL; KETOCONAZOLE; PACLITAXEL; PHENOBARBITAL; PHENYTOIN; QUERCETIN; QUINIDINE; RANITIDINE; RIFAMYCIN; TACROLIMUS; TERFENADINE; TOREMIFENE; TROLEANDOMYCIN;

ADVANCED CANCER; ANOREXIA; ARTHRALGIA; ARTICLE; ASTHENIA; BLOOD TOXICITY; BONE MARROW SUPPRESSION; CANCER CHEMOTHERAPY; CANCER GROWTH; CLINICAL ARTICLE; CLINICAL TRIAL; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DISEASE COURSE; DRUG EFFECT; DYSPNEA; FEMALE; FEVER; HUMAN; MULTICENTER STUDY; MYALGIA; NAUSEA; NEURITIS; NEUTROPENIA; OVARY CANCER; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; SIDE EFFECT; VOMITING;

EID: 0036445653     PISSN: 00908258     EISSN: None     Source Type: Journal    
DOI: 10.1006/gyno.2002.6762     Document Type: Article

References (55)

1. Canada NCIo. Canadian Cancer Statistics. Toronto: NCIC; 2001.
2. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin 1999;49(1):8-31.
3. Stuart G, Bertelsen K, Mangioni C, Trope CG, James K, Cassidy J, et al. Updated analysis shows a highly significant improved overall survival (OS) for cisplatin-paclitaxel as first line treatment of advanced ovarian cancer: Mature results of the EORTC-GCCG, NO-COVA, NCIC CTG and Scottish Intergroup Trial. ASCO 1998;17:361a.
4. Neijt JP, Hansen M, Hansen SW, Sorensen PG, Sessa C, Witteveen PO, et al. Randomized phase III study in previously untreated epithelial ovarian cancer FIG stage IIB, IIC, III, IV, comparing paclitaxelcisplatin and paclitaxel-carboplatin. ASCO 1997;16:352a.
5. Ozols RF, Bundy BN, Fowler J, Clarke-Pearson D, Mannel R, Hartenbach EM, et al. Randomized phase III study of cisplatin (CIS)/paclitaxel (PAC) versus carboplatin (CARBO)/PAC in optimal stage II epithelial ovarian cancer (OC): A Gynecologic Oncology Group Trial (GOG 158). ASCO 1999;18:356a.
6. du Bois A, Lueck HJ, Meier W, Moebus V, Costa SD, Bauknecht T, et al. Cisplatin/paclitaxel vs carboplatin/paclitaxel in ovarian cancer: Update of an Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Trial. ASCO 1999;18:356a.
7. Coukos G, Rubin SC. Chemotherapy resistance in ovarian cancer: New molecular perspectives. Obstet Gynecol 1998;91(5 Pt 1):783-92.
8. Dumontet C, Sikic BI. Mechanisms of action of and resistance to antitubulin agents: Microtubule dynamics, drug transport, and cell death. J Clin Oncol 1999;17(3):1061-70.
9. Fracasso PM. Overcoming drug resistance in ovarian carcinoma. Curr Oncol Rep 2001;3(1):19-26.
10. Arao S, Suwa H, Mandai M, Tashiro H, Miyazaki K, Okamura H, et al. Expression of multidrug resistance gene and localization of P- glycoprotein in human primary ovarian cancer. Cancer Res 1994;54(5):1355-9.
11. Noonan KE, Beck C, Holzmayer TA, Chin JE, Wunder JS, Andrulis IL, et al. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proc Natl Acad Sci USA 1990;87(18):7160-4.
12. van der Zee AG, Hollema H, de Jong S, Boonstra H, Gouw A, Willemse PH, et al. P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy. Cancer Res 1991;51(21):5915-20.
13. Holzmayer TA, Hilsenbeck S, Von Hoff DD, Roninson IB. Clinical correlates of MDR1 (P-glycoprotein) gene expression in ovarian and small-cell lung carcinomas. J Natl Cancer Inst 1992;84(19):1486-91.
14. Kavallaris M, Leary JA, Barrett JA, Friedlander ML. MDR1 and multidrug resistance-associated protein (MRP) gene expression in epithelial ovarian tumors. Cancer Lett 1996;102(1-2):7-16.
15. Izquierdo MA, van der Zee AG, Vermorken JB, van der Valk P, Belien JA, Giaccone G, et al. Drug resistance-associated marker Lrp for prediction of response to chemotherapy and prognoses in advanced ovarian carcinoma. J Natl Cancer Inst 1995;87(16):1230-7.
16. van der Zee AG, Hollema H, Suurmeijer AJ, Krans M, Sluiter WJ, Willemse PH, et al. Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas. J Clin Oncol 1995;13(1):70-8.
17. Rubin SC, Finstad CL, Hoskins WJ, Saigo PE, Provencher DM, Federici MG, et al. Expression of P-glycoprotein in epithelial ovarian cancer: Evaluation as a marker of multidrug resistance. Am J Obstet Gynecol 1990;163(1 Pt 1):69-73.
18. Nooter K, Westerman AM, Flens MJ, Zaman GJ, Scheper RJ, van Wingerden KE, et al. Expression of the multidrug resistance-associated protein (MRP) gene in human cancers. Clin Cancer Res 1995;1(11):1301-10.
19. Goldstein LJ. MDR1 gene expression in solid tumours. Eur J Cancer 1996;32A(6):1039-50.
20. Bourhis J, Goldstein LJ, Riou G, Pastan I, Gottesman MM, Benard J. Expression of a human multidrug resistance gene in ovarian carcinomas. Cancer Res 1989;49(18):5062-5.
21. Baekelandt M, Holm R, Nesland JM, Trope CG, Kristensen GB. Expression of apoptosis-related proteins is an independent determinant of patient prognosis in advanced ovarian cancer. J Clin Oncol 2000;18(22):3775-81.
22. Arts HJ, Katsaros D, de Vries EG, Massobrio M, Genta F, Danese S, et al. Drug resistance-associated markers P-glycoprotein, multidrug resistance-associated protein 1, multidrug resistance-associated protein 2, and lung resistance protein as prognostic factors in ovarian carcinoma. Clin Cancer Res 1999;5(10):2798-805.
23. Khalifa MA, Abdoh AA, Mannel RS, Walker JL, Angros LH, Min KW. P-glycoprotein as a prognostic indicator in pre- and postchemotherapy ovarian adenocarcinoma. Int J Gynecol Pathol 1997;16(1):69-75.
24. Schneider J, Rubio MP, Barbazan MJ, Rodriguez-Escudero FJ, Seizinger BR, Castresana JS. P-glycoprotein, HER-2/neu, and mutant p53 expression in human gynecologic tumors. J Natl Cancer Inst 1994;86(11):850-5.
25. Ford JM. Experimental reversal of P-glycoprotein-mediated multidrug resistance by pharmacological chemosensitisers. Eur J Cancer 1996;32A(6):991-1001.
26. Ferry DR, Traunecker H, Kerr DJ. Clinical trials of P-glycoprotein reversal in solid tumours. Eur J Cancer 1996;32A(6):1070-81.
27. Bradshaw DM, Arceci RJ. Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance. J Clin Oncol 1998;16(11):3674-90.
28. Germann UA, Shlyakhter D, Mason VS, Zelle RE, Duffy JP, Galullo V, et al. Cellular and biochemical characterization of VX-710 as a chemosensitizer: Reversal of P-glycoprotein-mediated multidrug resistance in vitro. Anticancer Drugs 1997;8(2):125-40.
29. Yanagisawa T, Newman A, Coley H, Renshaw J, Pinkerton CR, Pritchard-Jones K. BIRICODAR (VX-710; Incel): An effective chemosensitizer in neuroblastoma. Br J Cancer 1999;80(8):1190-6.
30. Rowinsky EK, Smith L, Wang YM, 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(9):2964-76.
31. Rustin GJ, Nelstrop AE, McClean P, Brady MF, McGuire WP, Hoskins WJ, et al. Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125. J Clin Oncol 1996;14(5):1545-51.
32. Zee B, Melnychuk D, Dancey J, Eisenhauer E. Multinomial phase II cancer trials incorporating response and early progression. J Biopharm Stat 1999;9(2):351-63.
33. Gianni L, Kearns CM, Giani A, Capri G, Vigano L, Lacatelli A, et al. Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 1995;13(1):180-90.
34. Huizing MT, Keung AC, Rosing H, van der Kuij V, ten Bokkel Huinink WW, Mandjes IM, et al. Pharmacokinetics of paclitaxel and metabolites in a randomized comparative study in platinum-pretreated ovarian cancer patients. J Clin Oncol 1993;11(11):2127-35.
35. Toppmeyer D, Seldman AD, Pollak M, Russell C, Tkaczuk K, Verma S, et al. Safety and efficacy of the MDR Inhibitor Incel (Biricodar; VX-710) in combination with paclitaxel for advanced breast cancer refractory to paclitaxel. Clin Cancer Res 2002;8(3):670-8.
36. Drach D, Zhao S, Drach J, Mahadevia R, Gattringer C, Huber H, et al. Subpopulations of normal peripheral blood and bone marrow cells express a functional multidrug resistant phenotype. Blood 1992;80(11):2729-34.
37. Chaudhary PM, Roninson IB. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 1991;66(1):85-94.
38. Ozols RF, Cunnion RE, Klecker RW, Jr., Hamilton TC, Ostchega Y, Parrillo JE, et al. Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J Clin Oncol 1987;5(4):641-7.
39. Hendrick AM, Harris AL, Cantwell BM. Verapamil with mitoxantrone for advanced ovarian cancer: A negative phase II trial. Ann Oncol 1991;2(1):71-2.
40. Markman M, Kennedy A, Webster K, Kulp B, Peterson G, Belinson J. Phase I trial of paclitaxel plus megestrol acetate in patients with paclitaxel-refractory ovarian cancer. Clin Cancer Res 2000;6(11):4201-4.
41. Baekelandt M, Lehne G, Trope CG, 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(12):2983-93.
42. Fields A, Hochster C, Runowicz J, Speyer J, Goldberg G, Cohen C, et al. SDZ PSC 833/paclitaxel in paclitaxel refractory ovarian carcinoma: A phase II trial with renewed responses. ASCO 1997;16:351a.
43. Fracasso PM, Brady MF, Moore DH, Walker JL, Rose PG, 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(12):2975-82.
44. Ling V. Multidrug resistance: Molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol 1997;40(Suppl):S3-8.
45. Dumontet C, Duran GE, Steger KA, Beketic-Oreskovic L, Sikic BI. Resistance mechanisms in human sarcoma mutants derived by single-step exposure to paclitaxel (Taxol). Cancer Res 1996;56(5):1091-7.
46. Ranganathan S, Benetatos CA, Colarusso PJ, Dexter DW, Hudes GR. Altered beta-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells. Br J Cancer 1998;77(4):562-6.
47. Kavallaris M, Kuo DY, Burkhart CA, Regl DL, Norris MD, Haber M, et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 1997;100(5):1282-93.
48. Montgomery RB, Guzman J, O'Rourke DM, Stahl WL. Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters beta-tubulin isotype expression. J Biol Chem 2000;275(23):17358-63.
49. Giannakakou P, Sackett DL, Kang YK, Zhan Z, Buters JT, Fojo T, et al. Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J Biol Chem 1997; 272(27):17118-25.
50. Gonzalez-Garay ML, Chang L, Blade K, Menick DR, Cabral F. A beta-tubulin leucine cluster involved in microtubule assembly and paclitaxel resistance. J Biol Chem 1999;274(34):23875-82.
51. Monzo M, Rosell R, Sanchez JJ, Lee JS, O'Brate A, Gonzalez-Larriba JL, et al. Paclitaxel resistance in non-small-cell lung cancer associated with beta-tubulin gene mutations. J Clin Oncol 1999;17(6):1786-93.
52. Srivastava RK, Mi QS, Hardwick JM, Longo DL. Deletion of the loop region of Bcl-2 completely blocks paclitaxel- induced apoptosis. Proc Natl Acad Sci USA 1999;96(7):3775-80.
53. Hengartner MO. The biochemistry of apoptosis. Nature 2000;407(6805):770-6.
54. Wang TH, Wang HS, Soong YK. Paclitaxel-induced cell death: Where the cell cycle and apoptosis come together. Cancer 2000;88(11):2619-28.
55. Bridgewater JA, Nelstrop AE, Rustin GJ, Gore ME, McGuire WP, Hoskins WJ. Comparison of standard and CA-125 response criteria in patients with epithelial ovarian cancer treated with platinum or paclitaxel. J Clin Oncol 1999;17(2):501-8.