Phase II trial of dexverapamil and epirubicin in patients with non-responsive metastatic breast cancer

British Journal of Cancer

Volumn 77, Issue 7, 1998, Pages 1155-1163

  Lehnert, M ^a,e   Mross, K ^b,f   Schueller, J ^c   Thuerlimann, B ^a   Kroeger, N ^b   Kupper, H ^d  

^a CANTONAL HOSPITAL ST GALLEN   (Switzerland)

^b UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^c KRANKENANSTALT RUDOLFSTIFTUNG   (Austria)

^d Knoll AG   (Germany)

^e NATIONAL UNIVERSITY HOSPITAL   (Singapore)

^f UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Anthracycline resistance; Breast cancer; Dexverapamil

Indexed keywords

DEXVERAPAMIL; EPIRUBICIN; GLYCOPROTEIN P;

ADULT; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BLEEDING; BREAST CANCER; CANCER REGRESSION; CHEMOSENSITIVITY; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG BLOOD LEVEL; FEMALE; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; METASTASIS; MUCOSA INFLAMMATION; MULTIDRUG RESISTANCE; NAUSEA; NEUTROPENIA; ORAL DRUG ADMINISTRATION; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; VOMITING;

EID: 0031881790     PISSN: 00070920     EISSN: None     Source Type: Journal    
DOI: 10.1038/bjc.1998.192     Document Type: Article

References (68)

1. Baldini N, Scotlandi K, Barbanti-Brodano G, Manara MC, Maurici D, Bacci G, Bertoni F, Picci P, Sottilis, Campanacci M and Serra M (1995) Expression of P-glycoprotein in high-grade osteosarcoma in relation to clinical outcome. N Engl J Med 333: 1380-1385
2. Bartlett NL, Lum BL, Fisher G, Brophy NA, Ehsan MN, Halsey J and Sikic BI (1994) Phase I trial of doxorubicin with cyclosporine as a modulator of multidrug resistance. J Clin Oncol 12: 835-842
3. Bates SE, Meadows B, Goldspiel BR, Denicoff A, Tung BL, Tucker E, Steinberg S and Elwood LJ (1995) A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer. Cancer Chemother Pharmacol 35: 457-163
4. Beck WT, Grogan TM, Willman CL, Cordon-Cardo C, Parham DM, Kuttesch JF, Andreeff M, Bates SE, Berard CW, Boyett JM, Brophy NA, Broxterman HJ, Chan HSL, Dalton WS, Dietel M, Fojo AT, Gascoyne RD, Head D, Houghton PJ, Srivastava DK, Lehnert M, Leith CP, Paietta E, Pavelic ZP, Rimsza L, Roninson IB, Sikic BI, Twentyman PR, Warnke R and Weinstein R (1996) Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations. Cancer Res 56: 3010-3020
5. Berg SL, Tolcher A, O'Shaughnessy JA, Denicoff AM, Noone M, Ognibene FP, Cowan KH and Balis FM (1995) Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer. J Clin Oncol 13: 2039-2042
6. 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
7. Boote DJ, Dennis IF, Twentyman PR, Osborne RJ, Laburte C, Hensel S, Smyth JF, Brampton MH and Bleehen NM (1996) Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J Clin Oncol 14: 610-618
8. Brodsky SJ, Cutler SS, Weiner DA and Klein MD (1981) Hepatotoxicity due to treatment with verapamil. Ann Intern Med 94: 490-491
9. Broxterman HJ, Lankelma J and Pinedo HM (1996) How to probe tumour samples for P-glycoprotein and multidrug resistance-associated protein. Eur J Cancer 32A: 1024-1033
10. Budd GT, Bukowski RM, Lichtin A, Bauer L, Van Kirk P and Ganapathi R (1993) Phase II trial of doxorubicin and trifluoperazine in metastatic breast cancer. Invest New Drugs 11: 75-79
11. Chan HSL, Thorner PS, Haddad G and Ling V (1990) Immunohistochemical detection of P-glycoprotein: prognostic correlation in soft tissue sarcoma of childhood. J Clin Oncol 8: 689-704
12. Chan HSL, Haddad G, Thorner PS, DeBoer G, Lin YP, Ondrused N, Yeger H and Ling V (1991) P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma. N Engl J Med 325: 1608-1614
13. Echizen H, Brecht T, Niedergesaess S, Vogelsang B and Eichelbaum M (1985) The effect of dextro-levo- and racemic verapamil on atrio-ventricular conduction in humans. Am Heart J 109: 210-217
14. Ferry DR, Traunecker H and Kerr DJ (1996) Clinical trials of P-glycoprotein reversal in solid tumours. Eur J Cancer 32A: 1070-1081
15. Fisher GA, Lum BL, Hausdorff J and Sikic BI (1996) Pharmacological considerations in the modulation of multidrug resistance. Eur J Cancer 32A: 1082-1088
16. Ford JM (1996) Experimental reversal of P-glycoprotein-mediated multidrug resistance by pharmacological chemosensitisers. Eur J Cancer 32A: 991-1001
17. Gehan EA and Schneiderman MA (1982) Experimental design of clinical trials. In Cancer Medicine, Holland JF and Frei E III. (eds), pp. 531-553. Lea and Febiger: Philadelphia
18. Goldstein LJ (1996) MDR1 gene expression in solid tumours. Eur J Cancer 32A: 1039-1050
19. Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM, Lieber M, Cossman J, Gottesman MM and Pastan I (1989) Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81: 116-124
20. Gottesman MM and Pastan I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Ann Rev Biochem 62: 385-427
21. Gruber A, Peterson C and Reizensten P (1988) D-verapamil and L-verapamil are equally effective in increasing vincristine accumulation in leukemic cells in vitro. Int J Cancer 41: 224-226
22. Harapat SR and Kates RE (1980) High-performance liquid chromatographic analysis of verapamil. J Chromatogr 181: 484-489
23. Hausmaninger H, Lehnert M, Steger G, Sevelda P, Tschurtschenthaler G, Hehenwarter W, Fridrik M, Samonigg H, Schiller L, Manfreda D, Haidinger R, Kienzer R and Kemmler G (1995) Randomized phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer. Eur J Cancer 31A: 2169-2173
24. Hayward JL, Carbone PP, Heuson JC, Rubens ED, Kumaoka S and Segaloff A (1977) Assessment of response to therapy in advanced breast cancer. Eur J Cancer 13: 89-94
25. Kaye SB (1997) Multidrug resistance in breast cancer - is the jury in yet? J Natl Cancer Inst 89: 902-903
26. Kerr DJ, Graham J, Cummings J, Morrison JG, Thompson GG, Brodie MJ and Kaye SB (1986) The effect of verapamil on the pharmacokinetics of adriamycin. Cancer Chemother Pharmacol 18: 239-242
27. Lehnert M (1996) Clinical multidrug resistance in cancer: a multifactorial problem. Eur J Cancer 32A: 912-920
28. Lehnert M, De Giuli R and Twenty-man PR (1996) A sensitive and rapid bioassay for analysis of P-glycoprotein-inhibiting activity of chemosensitizers in patient serum. Clin Cancer Res 2: 403-110
29. Linn SC, Giaccone G, Van Diest PJ, Blokhuis WMD, Van Der Valk P, Van Kalken CK, Kuiper CM, Pinedo HM and Baak JPA (1995) Prognostic relevance of P-glycoprotein expression in breast cancer. Ann Oncol 6: 679-685
30. List AF, Spier C, Greer J, Wolff S, Hutter J, Dorr R, Salmon SE, Futscher B, Baier M and Dalton W (1993) Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J Clin Oncol 11: 1652-1660
31. Lum BL, Kraubisch S, Yahanda AM, Adler KM, Jew L, Ehsan MN, Brophy NA, Hlasey J, Gosland MP and Sikic BI (1992) Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J Clin Oncol 10: 1635-1642
32. Maessen P, Mross K, Pinedo HM and Van Der Vijgh WJF (1987) Improved method for the determination of 4′-epidoxorubicin and seven metabolites in plasma by high-performance liquid chromatography. J Chromatogr 417: 339-346
33. Marie J-P, Zhoud-S, Gurbuxani S, Legrand O and Zittoun R (1996) MDR1/P-glycoprotein in haematological neoplasms. Eur J Cancer 32A: 1034-1038
34. Marschner N, Kreienberg R, Souchon R, Räth U, Eggeling B, Voigtmann R, Ruffert K, Schütte M, Ammon A, Kesztyüs T, Kaplan E and Nagel G (1994) Evaluation of the importance and relevance of dose intensity using epirubicin and cyclosphosphamide in metastatic breast cancer: interim analysis of a prospective randomized trial. Semin Oncol 21: 10-16
35. Merkel DE, Fuqua SAW, Tandon AK, Hill SM, Buzdar AU and McGuire WL (1989) Electrophoretic analysis of 248 clinical breast cancer specimens for P-glycoprotein overexpression or gene amplification. J Clin Oncol 7: 1129-1136
36. Merry S, Flanigan P, Schlick E, Freshney RI and Kaye SB (1989) Inherent adriamycin resistance in a murine tumour line: circumvention with verapamil and norverapamil. Br J Cancer 59: 895-897
37. Miller AB, Hoogstraten B, Staquet M and Winkler A (1981) Reporting results of cancer treatment. Cancer 47: 207-214
38. Miller TP, Grogan TM, Dalton WS, Spier CM, Scheper RJ and Salmon SE (1991) P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J Clin Oncol 9: 17-24
39. Millward MJ, Cantwell BMJ, 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
40. Motzer RJ, Lyn P, Fischer P, Lianes P, Ngo RL, Cordon-Cardo C and O'Brien JP (1995) Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma. J Clin Oncol 13: 1958-1965
41. Mross K, Mayer U, Hamm K and Hossfeld DK (1990) High-performance liquid chromatography of iodo-doxorubicin and fluorescent metabolites in plasma samples. J Chromatogr 530: 192-199
42. Mross K, Bohn C, Edler L, Jonat W, Queisser W, Heidemann E, Goebel M and Hossfeld DK (1993a) Randomized phase II study of single-agent epirubicin ± verapamil in patients with advanced metastatic breast cancer. Ann Oncol 4: 45-50
43. Mross K, Hamm K and Hossfeld DK (1993b) Effects of verapamil on the pharmacokinetics and metabolism of epirubicin. Cancer Chemother Pharmacol 31: 369-375
44. Murren JR, Durivage HJ, Buzaid AC, Reiss M, Flynn SD, Carter D and Hait WN (1996) Trifluoperazine as a modulator of multidrug resistance in refractory breast cancer. Cancer Chemother Pharmacol 38: 65-70
45. Nash DT and Drumheller Feer T (1983) Hepatic injury possibly induced by verapamil. JAMA 249: 395-396
46. Neugebaucr G (1978) Comparative cardiovascular actions of verapamil and its major metabolites in the anaesthetised dog. Cardiovas Res 12: 247-254
47. Ozols RF, Cunnion RE, Klecker RW, Hamilton TC, Ostchega Y, Perillo JE and Young RC (1987) Verapamil and Adriamycin in the treatment of drug-resistant overian cancer patients. J Clin Oncol 5: 641-647
48. Pennock GD, Dalton WS, Roeske WR, Appleton AP, Mosley K, Plezia P, Miller TP and Salmon SE (1991) Systemic toxic effects associated with high-dose verapamil infusion and chemotherapy administration. J Natl Cancer Inst 83: 105-110
49. Philip PA, Joel S, Monkman SC, Dolega-Ossowski E, Tonkjin K, Carmichael J, Idle JR and Harris AL (1992) A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide. Br J Cancer 65:267-270
50. Pinedo HM and Giaccone G (1995) P-glycoprotein - a marker of cancer-cell behavior. N Engl J Med 333: 1417-1419
51. Pirker R, Keilhauer G, Raschak M, Lechner C and Ludwig H (1990) Reversal of multi-drug resistance in human KB cell lines by structural analogs of Verapamil. Int J Cancer 45: 916-919
52. Pirker R, Wallner J, Geissler K, Linkesch W, Haas OA, Bettelheim P, Hopfner M, Scherrer R, Valent P, Havelec L, Ludwig H and Lechner K (1991) MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst 83: 708-712
53. Ries F and Dicato M (1991) Treatment of advanced and refractory breast cancer with doxorubicin, vincristine and continuous infusion of verapamil. A phase I-II clinical trial. Med Oncol Tumor Pharmacother 8: 39-43
54. Salmon SE, Dalton WS, Grogan TM, Plezia P, Lehnert M, Roe DJ and Miller TM (1991) Multidrug-resistant myeloma, laboratory and clinical effects of verapamil as a chemosensitizer. Blood 78: 44-50
55. Sanfilippo O, Ronchi E, De Marco C Di Fronzo G and Silvestrine R (1991) Expression of P-glycoprotein in breast cancer tissue and in vitro resistance to doxorubicin and vincristine. Eur J Cancer 27: 155-158
56. Scheithauer W, Schenk T and Czeika M (1993) Pharmacokinetic interaction between epirubicin and the multidrug resistance reverting agent D-verapamil. Br J Cancer 68: 8-9
57. Sikic BI (1993) Modulation of multidrug resistance: at the threshold. J Clin Oncol 11: 1629-1635
58. Sonneveld P (1996) Reversal of multidrug resistance in acute myeloid leukaemia and other haematological malignancies. Eur J Cancer 32A: 1062-1069
59. Sonneveld P, Durie BGM, Lokhorst HM, Marie JP, Solbu G, Suciu S, Zittoun R, Löwenberg B and Noter K (1992) Modulation of multidrug-resistant multiple myeloma with cyclosporin. Lancet 340: 255-259
60. Trock BJ, Leonessa F and Clarke R (1997) Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst 89: 917-931
61. Van Kalken CK, Van Der Hoeven JJM, De Jong J, Giaccone G, Schuurhuis GJ, Maessen PA, Blokhuis WMD, Van Der Vijgh WJF and Pinedo HM (1991) Bepridil in combination with anthracyclines to reverse anthracycline resistance in cancer patients. Eur J Cancer 27: 739-744
62. Verrelle P, Meissonnier F, Fonck Y, Feillel V, Dionet C, Kwiatkowski F, Plagne R and Chassagne J (1991) Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma. J Natl Cancer Inst 83: 111-116
63. Wallner J, Depisch D, Hopfner M, Haider K, Spona J, Ludwig H and Pirker R (1991) MDR1 gene expression and prognostic factors in primary breast carcinomas. Eur J Cancer 27: 1352-1355
64. Wilson WH, Jami-Dow C, Bryant G, Balis FM, Klecker RW, Bates SE, Chabner BA, Steinberg SM, Kohler DR and Wittes RE (1995a) Phase I and pharmacokinetic study of the multidrug resistance modulator dexverapamil with EPOCH chemotherapy. J Clin Oncol 13: 1985-1994
65. Wilson WH, Bates SE, Fojo A, Bryant G, Zhan Z, Regis J, Wittes RE, Jaffe ES, Steinberg SM, Herdt J and Chabner B (1995b) Controlled trial of dexverapamil, a modulator of multidmg resistance, in lymphomas refractory to EPOCH chemotherapy. J Clin Oncol 13: 1995-2004
66. Wishart GC, Plumb JA, Going JJ, McNicol AM, McArdle CS, Tsuruo T and Kaye SB (1990) P-glycoprotein expression in primary breast cancer detected by immunocytochemistry with two monoclonal antibodies. Br J Cancer 62:758-761
67. Wishart GC, Plumb JA, Morrison JG, Hamilton TG and Kaye SB (1992) Adequate tumor quinidine levels for multidrug resistance modulation can be achieved in vivo. Eur J Cancer 28: 28-31
68. Wishart GC, Bissett D, Paul J, Jodrell D, Harnett A, Habeshaw T, Kerr DJ, Macham MA, Soukop M, Leonard RCF, Knepil J and Kaye SB (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