Vinflunine: Review of a new vinca alkaloid and its potential role in oncology

Journal of Oncology Pharmacy Practice

Volumn 17, Issue 3, 2011, Pages 209-224

  Ng, John S ^a,b  

^a WOLFSON CHILDREN S HOSPITAL   (United States)

^b UNIVERSITY OF FLORIDA HEALTH   (United States)

Author keywords

solid tumor; vinca alkaloid; vinflunine

Indexed keywords

BEVACIZUMAB; CAMPTOTHECIN; CAPECITABINE; CARBOPLATIN; CETUXIMAB; CISPLATIN; DEXAMETHASONE; DOCETAXEL; DOXORUBICIN; ERLOTINIB; ETOPOSIDE; EVEROLIMUS; FLUOROURACIL; GEMCITABINE; GLYCOPROTEIN P; IRINOTECAN; IXABEPILONE; METHOTREXATE; MITOMYCIN C; NAVELBINE; PACLITAXEL; PEMETREXED; SORAFENIB; SUNITINIB; TEMSIROLIMUS; TRASTUZUMAB; UNINDEXED DRUG; VINBLASTINE; VINCRISTINE; VINFLUNINE;

ABDOMINAL PAIN; ADD ON THERAPY; ADULT RESPIRATORY DISTRESS SYNDROME; ALOPECIA; ANEMIA; ANOREXIA; ANTIANGIOGENIC ACTIVITY; APOPTOSIS; ARTHRALGIA; BINDING SITE; BONE PAIN; BREAST CANCER; CANCER GROWTH; CANCER RADIOTHERAPY; CONSTIPATION; DEHYDRATION; DRUG DOSE REDUCTION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DYSPHAGIA; DYSPNEA; EMBOLISM; FATIGUE; FEBRILE NEUTROPENIA; FLU LIKE SYNDROME; HEART MUSCLE ISCHEMIA; HUMAN; HYPONATREMIA; ILEUS; IN VITRO STUDY; IN VIVO STUDY; INFECTION; INJECTION SITE REACTION; INTRACELLULAR TRANSPORT; JAW PAIN; KIDNEY CARCINOMA; KIDNEY DYSFUNCTION; LEUKOPENIA; LOADING DRUG DOSE; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; METASTASIS INHIBITION; METASTATIC BREAST CANCER; MICROTUBULE; MONOTHERAPY; MUCOSA INFLAMMATION; MULTIDRUG RESISTANCE; MULTIPLE CYCLE TREATMENT; MYALGIA; NAUSEA; NEUROPATHIC PAIN; NEUROPATHY; NEUTROPENIA; NONHUMAN; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PLEURA MESOTHELIOMA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROSTATE CANCER; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SALVAGE THERAPY; SENSORY NEUROPATHY; SEPSIS; SEPTIC SHOCK; SIDE EFFECT; SOLID TUMOR; STOMACH ADENOCARCINOMA; STOMATITIS; SURVIVAL RATE; SYNCOPE; THORAX PAIN; THROMBOCYTOPENIA; THROMBOSIS; TRANSITIONAL CELL CARCINOMA; URINARY EXCRETION; VOMITING; WEIGHT REDUCTION;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; NEOPLASMS; TREATMENT OUTCOME; TUBULIN MODULATORS; VINBLASTINE;

EID: 80053319586     PISSN: 10781552     EISSN: 1477092X     Source Type: Journal    
DOI: 10.1177/1078155210373525     Document Type: Review

References (129)

1. Rowinsky EK and Donehower RC Antimicrotubule agents. In: Chabner BA, Longo DL (eds) Cancer chemotherapy and biotherapy. NY: Lippincott-Raven Publishers, 1996, p. 263-296.
2. Bhat KMR and Setaluri V. Microtubule-associated proteins as targets in cancer chemotherapy. Clin Cancer Res 2007 ; 13 (10). 2849-2854. (Pubitemid 46849557)
3. Horwitz SB Semin Oncol 2008 ; 35 (Suppl. 3). S1 - S2.
4. Teicher BA Newer cytotoxic agents: attacking cancer broadly. Clin Cancer Res 2008 ; 14 (6). 1610-1617. (Pubitemid 351469444)
5. Noble RL, Beer CT and Cutts JH Further biological activities of vinca leukoblastine - an alkaloid isolated from Vinca rosea (L.). Biochem Pharmacol 1958 ; 1: 347-348.
6. Jordan MA, Horwitz SB, Lobert S. and Correia JJ Exploring the mechanisms of action of the novel microtubule inhibitor vinflunine. Semin Oncol 2008 ; 35 (Suppl 3). S6 - S12.
7. Svoboda GH Alkaloids of Vinca rosea Linn. IX. Extraction and characterisation of leurosidine and leucocristine. Lloyda 1961 ; 24: 173-178.
8. Johnson SA, Harper P., Hortobagyi GN and Pouillart P. Vinorelbine: an overview. Cancer Treat Rev 1996 ; 22 (2). 127-142. (Pubitemid 26235725)
9. Fahy J., Hellier P., Breillout F. and Bailly C. Vinflunine: discovery and synthesis of a novel microtubule inhibitor. Semin Oncol 2008 ; 35 (Suppl. 3). S3 - S5.
10. Rowinsky EK and Tolcher A. Antimicrotubule agents. In: DeVita Jr VT, Hellman S, Rosenberg SA (eds) Cancer principles & practice of oncology, 7 th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2005, p. 390-416.
11. Sheng LX, Da YX, Long Y., et al. Synthesis and biological evaluation of C-12' substituted vinflunine derivatives. Bioorg Med Chem Lett 2008 ; 18: 4602-4605.
12. Langlois N., Gueritte F., Langlois Y. and Potier P. Application of a modification of the Polonovski reaction to the synthesis of vinblastine-type alkaloids. J Am Chem Soc 1976 ; 98 (22). 7017-7024.
13. Mangeney P., Andriamialisoa RZ, Langlois N., Langlois Y. and Potier P. A new class of antitumor compounds: 5'-nor and 5',6'-seco derivatives of vinblastine type alkaloids. J Org Chem 1979 ; 44 (22). 3765-3768. (Pubitemid 10169595)
14. Fahy J., Duflos A., Ribet JP, et al. Vinca alkaloids in superacidic media: a method for creating a new family of antitumor derivatives. J Am Chem Soc 1997 ; 119 (36). 8576-8577. (Pubitemid 27404589)
15. Jacquesy JC and Fahy J. Cancer: superacid generation of new antitumor agents. In: Torrence PF (ed.) Biomedical chemistry: applying chemical principles to the understanding and treatment of disease. New York, NY: Wiley-Interscience, 2000, p. 227-246.
16. Fahy J. Modifications in the 'upper' velbenamine part of the vinca alkaloids have major implications for tubulin interacting activities. Curr Pharm Des 2001 ; 7: 1181-1197. (Pubitemid 32798803)
17. Bennouna J., Delord JP, Campone M. and Nguyen L. Vinflunine: a new microtubule inhibitor agent. Clin Cancer Res 2008 ; 14 (6). 1625-1632. (Pubitemid 351469446)
18. Jordan MA, Thrower D. and Wilson L. Mechanism of inhibition of cell proliferation by vinca alkaloids. Cancer Res 1991 ; 51 (8). 2212-2222.
19. Jordan MA and Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004 ; 4 (4). 253-265. (Pubitemid 38525281)
20. Kruczynski A., Barret JM, Etievant C., Colpaert F., Fahy J. and Hill BT Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated vinca alkaloid. Biochem Pharmacol 1998 ; 55 (5). 635-648. (Pubitemid 28077822)
21. Pourroy B., Carre M., Honore S., et al. Low concentrations of vinflunine induce apoptosis in human SK-N-SH neuroblastoma cells through a postmitotic G1 arrest and a mitochondrial pathway. Mol Pharmacol 2004 ; 66 (3). 580-591. (Pubitemid 39329257)
22. Simoens C., Vermorken JB, Korst AE, et al. Cell cycle effects of vinflunine, the most recent promising vinca alkaloid and its interaction with radiation, in vitro. Cancer Chemother Pharmacol 2006 ; 58 (2). 210-218.
23. Lobert S. and Puozzo C. Pharmacokinetics, metabolites, and preclinical safety of vinflunine. Semin Oncol 2008 ; 35 (Suppl 3). S28 - S33.
24. Kruczynski A., Etievant C., Perrin D., Chansard N., Duflos A. and Hill BT Characterization of cell death induced by vinflunine, the most recent vinca alkaloid in clinical development. Br J Cancer 2002 ; 86 (1). 143-150. (Pubitemid 34146355)
25. Kruczynski A. and Hill BT Vinflunine, the latest vinca alkaloid in clinical development. A review of its preclinical anticancer properties. Crit Rev Oncol Hematol 2001 ; 40 (2). 159-173. (Pubitemid 33001600)
26. Jean-Decoster C., Brichese L., Barrett JM, Tollon Y., Kruczynski A. and Hill BT Vinflunine, a new vinca alkaloid: cytotoxicity, cellular accumulation and action on the interphasic and mitotic microtubule cytoskeleton of PtK2 cells. Anticancer Drugs 1999 ; 10: 537-543. (Pubitemid 29410800)
27. Hill BT, Fiebig HH, Waud WR, Poupon MF, Colpaert F. and Kruczynski A. Superior in vivo experimental antitumour activity of vinflunine, relative to vinorelbine, in a panel of human tumour xenografts. Eur J Cancer 1999 ; 35 (3). 512-520. (Pubitemid 29151954)
28. Pasquier E., Honore S., Pourrou B., et al. Antiangiogenic concentrations of paclitaxel induce an increase in microtubule dynamics in endothelial cells but not in cancer cells. Cancer Res 2005 ; 65: 2433-2440. (Pubitemid 40490155)
29. Kruczynski A., Poli M., Dossi R., et al. Antiangiogenic, vascular-disrupting and antimetastatic activities of vinflunine, the latest vinca alkaloid in clinical development. Eur J Cancer 2006 ; 42: 2821-2832. (Pubitemid 44584664)
30. Honore S., Pagano A., Gauthier G., et al. Antiangiogenic vinflunine affects EB1 localization and microtubule targeting to adhesion sites. Mol Cancer Ther 2008 ; 7 (7). 2080-2089.
31. Holwell SE, Hill BT and Bibby MC Anti-vascular effects of vinflunine in the MAC 15A transplantable adenocarcinoma model. Br J Cancer 2001 ; 84: 290-295. (Pubitemid 32113459)
32. Johnson P., Geldart T., Fumoleau P., Pinel M. -C, Nguyen L. and Judson I. Phase I study of vinflunine administered as a 10-minute infusion on days 1 and 8 every 3 weeks. Invest New Drugs 2006 ; 24: 223-231. (Pubitemid 43738961)
33. Vermoken JB, Stupp R., Nguyen L., et al. Phase I study of i.v. vinflunine given on a weekly schedule in previously untreated patients with advanced solid tumours. (abstract 887). Proc Am Soc Clin Oncol 2003 ; 22: 221.
34. Zhao XP, Liu XQ, Wang YS, Wang H. and Wang GJ Pharmacokinetics, tissue distribution and excretion of vinflunine. Eur J Drug Metab Pharmacokinet 2006 ; 31 (2). 59-64. (Pubitemid 44166282)
35. Zhao X., Zhong J., Liu X. and Wang G. CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes. Acta Pharmacol Sin 2007 ; 28 (1). 118-124. (Pubitemid 46046635)
36. Dominique BR, Bascale G., Christian P., et al. Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine. Fundam Clin Pharmacol 2005 ; 19: 545-553.
37. Bennouna J., Fumoleau P., Armand JP, et al. Phase I and pharmacokinetic study of the new vinca alkaloid vinflunine administered as a 10-min infusion every 3 weeks in patients with advanced solid tumours. Ann Oncol 2003 ; 14: 630-637. (Pubitemid 41295094)
38. Bennouna J., Campone M., Delord JP and Pinel MC Vinflunine: a novel antitubulin agent in solid malignancies. Expert Opin Investig Drugs 2005 ; 14: 1259-1267. (Pubitemid 41488874)
39. Pastan I. and Gottesman MM Multidrug resistance. Annu Rev Med 1991 ; 42: 277-286.
40. Hill BT Differing patterns of cross-resistance resulting from exposure to specific antitumour drugs or to radiation in vitro. Cytotechnology 1993 ; 12: 265-288.
41. Hill BT, Whelan RD, Shellard SA, McLean S. and Hosking L. Differential cytotoxic effects of docetaxel in a range of mammalian tumor cell lines and certain drug resistant sublines in vitro. Invest New Drugs 1994 ; 12: 169-182. (Pubitemid 24376401)
42. Etievant C., Barret JM, Krczynski A., Perrin D. and Hill BT Vinflunine (20',20'-difluoro-3',4'-dihydrovinorelbine), a novel vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro. Invest New Drugs 1998 ; 16: 3-17. (Pubitemid 28379411)
43. Ueda K., Cardarelli C., Gottesman MM and Pastan I. Expression of a full-length cDNA for the human 'MDR1' gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci USA 1987 ; 84: 3004-3008. (Pubitemid 17064766)
44. Ambudkar SV, Dey S., Krycyna CA, Ramachandra M., Pastan I. and Gottesman MM Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 1999 ; 39: 361-398. (Pubitemid 29222564)
45. Dean M., Rzhetsky A. and Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 2001 ; 11: 1156-1166. (Pubitemid 32677289)
46. Gottesman MM and Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Med 1993 ; 62: 385-427. (Pubitemid 23237876)
47. Esteve MA, Carre M., Bourgarel-Rey V., et al. Bcl-2 down-regulation and tubulin subtype composition are involved in resistance of ovarian cancer cells to vinflunine. Mol Cancer Ther 2006 ; 5 (11). 2824-2833. (Pubitemid 44849009)
48. Carre M. and Braguer D. Microtubule damaging agents and apoptosis. In: Fojo T (ed.) Role of microtubules in cell biology, neurobiology, and oncology. Totowa, NJ: Humana Press, 2008, p. 479-518.
49. Etievant C., Kruczynski A., Barret JM, Tait AS, Kavallaris M. and Hill BT Markedly diminished drug resistance-inducing properties of vinflunine (20',20'difluoro-3',4'-dihydrovinorelbine) relative to vinorelbine, identified in murine and human tumour cells in vivo and in vitro. Cancer Chemother Pharmacol 2001 ; 48 (1). 62-70. (Pubitemid 32662438)
50. Bennouna J., Breton JL, Tourani JM, et al. Vinflunine-an active chemotherapy for treatment of advanced non-small-cell lung cancer previously treated with a platinum-based regimen: results of a phase II study. Br J Cancer 2006 ; 94: 1383-1388. (Pubitemid 43772270)
51. Bonfil RD, Russo DM, Binda MM, Delgado FM and Vincenti M. Higher antitumor activity of vinflunine than vinorelbine against an orthotopic murine model of transitional cell carcinoma of the bladder. Urol Oncol 2002 ; 7: 159-166.
52. Culine S., Theodore C., De Santis M., et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer 2006 ; 94: 1394-1401.
53. Erjala K., Raitanen M., Kulmala J. and Grenman R. Head and neck carcinoma cell lines are sensitive to vinflunine in vitro. Anticancer Res 2005 ; 25 (6B). 4363-4367. (Pubitemid 41665229)
54. Crown J. Optimising treatment outcomes: a review of current management strategies in first-line chemotherapy of metastatic breast cancer. Eur J Cancer 1997 ; 33: S15 - S19.
55. Bunn Jr A. and Kelly K. New chemotherapeutic agents prolong survival and improve quality of life in non-small cell lung cancer: a review of the literature and future directions. Clin Cancer Res 1998 ; 4: 1087-1200.
56. Barret JM, Etievant C. and Hill BT In vitro synergistic effects of vinflunine, a novel fluorinated vinca alkaloid, in combination with other anticancer drugs. Cancer Chemother Pharmacol 2000 ; 45 (6). 471-476. (Pubitemid 30316907)
57. Shnyder SD, Cooper PA, Gyselinck N., Hill BT, Double JA and Bibby MC Vinflunine potentiates the activity of cisplatin but not 5-fluorouracil in a transplantable murine adenocarcinoma model. Anticancer Res 2003 ; 23 (6C). 4815-4820. (Pubitemid 38173901)
58. Edelstein MP, Wolfe LA and Duch DS Potentiation of radiation therapy by vinorelbine (Navelbine) in nonsmall cell lung cancer. Semin Oncol 1996 ; 23: 41-47. (Pubitemid 26130114)
59. Fukuoka K., Arioka H., Iwamoto Y., et al. Mechanism of the radiosensitization induced by vinorelbine in human non-small cell lung cancer cells. Lung Cancer 2001 ; 34: 451-460. (Pubitemid 33041481)
60. Simoens C., Lardon F., Pauwels B., et al. Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, in vitro. BMC Cancer 2008 ; 8: 65.
61. Simoens C., Pauwels B., Vermorken J., et al. Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro. Cancer Chemother Pharmacol 2008 ; 62: 183-193. (Pubitemid 351692072)
62. Fukuoka K., Arioka H., Iwamoto Y., et al. Mechanism of vinorelbine-induced radiosensitization of human small cell lung cancer cells. Cancer Chemother Pharmacol 2002 ; 49: 385-390. (Pubitemid 34439339)
63. Erjala K., Pulkkinen J., Kulmala J. and Grenman R. Concomitant vinorelbine and radiation in head and neck squamous cell carcinoma in vitro. Acta Oncol 2004 ; 43: 169-174. (Pubitemid 38478903)
64. Sinclair WK and Morton RA X-ray sensitivity during the cell generation cycle of cultured Chinese hamster cells. Radiat Res 1966 ; 29: 450-474.
65. Terasima R. and Tolmach LJ X-ray sensitivity and DNA synthesis in synchronous populations of HeLa cells. Science 1963 ; 140: 490-492.
66. Goldstein D., Ackland SP, Bell DR, et al. Phase II study of vinflunine in patients with metastatic renal cell carcinoma. Invest New Drugs 2006 ; 24 (5). 429-434. (Pubitemid 43876079)
67. Bunn PA Chemotherapy for advanced non-small-cell lung cancer: who, what, when, why? J Clin Oncol 2002 ; 20 (Suppl. 18). S23 - S33.
68. Natale RB Gemcitabine-containing regimens versus others in first-line treatment of NSCLC. Oncology 2004 ; 18 (Suppl. 5). 27-31.
69. Le Chevalier T., Scagliotti G., Natale R., et al. Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced nonsmall-cell lung cancer: a meta-analysis of survival outcomes. Lung Cancer 2005 ; 47: 69-80. (Pubitemid 39643243)
70. Kelly K., Crowley J., BunnJr PA, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: a southwest oncology group trial. J Clin Oncol 2001 ; 19: 3210-3218. (Pubitemid 32591438)
71. Schiller JH, Harrington D., Belani C., et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med 2002 ; 346: 92-98. (Pubitemid 34438899)
72. Shepherd FA, Dancey J., Arnold A., et al. Phase II study of pemetrexed disodium, a multitargeted antifolate, and cisplatin as first-line therapy in patients with advance non-small cell lunch carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group. Cancer 2001 ; 92: 595-600. (Pubitemid 32735195)
73. Magnegold C., Gatzemeier U., von Pawel J., et al. Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, pemetrexed disodium, ALIMTA) and cisplain: a multicenter phase II trial. Ann Oncol 2000 ; 11: 435-440.
74. Krzakowski M., Douillard J., Ramlau R., et al. Phase III study of vinflunine versus docetaxel in patients with advanced non-small cell lung cancer (NSCLC) previously treated with a platinum-containing regimen (abstract 7511). J Clin Oncol 2007 ; 25: 4278.
75. US National Institutes of Health. Vinflunine and cetuximab as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer. http://clinicaltrials.gov/ct2/show/NCT00519831?term=vinflunine&rank= 12 (accessed May 2010 ).
76. Tourani K., Pinel M., Planchard D., Aslanis V., Gouva S. and Robinet G. Phase I and pharmacokinetic study of vinflunine (VFL) in combination with carboplatin (CBDCA) for treatment of advanced non-small cell lung cancer (NSCLC) in chemonaive patients: final results (abstract 7271). J Clin Oncol 2005 ; 23 (16S). S688.
77. Ramlau R., Souquet P-J., Sun X., et al. Results of a phase I/II and pharmacokinetic study of vinflunine (VFL) in combination with cisplatin (CDDP) for primary treatment of advanced non-small cell lung cancer (NSCLC) (abstr 7110). J Clin Oncol 2004 ; 22: 2723.
78. Ettinger DS and Aisner J. Changing face of small-cell lung cancer: real and artifact. J Clin Oncol 2006 ; 24: 4526.
79. MacCallum C. and Gillenwater HH Second-line treatment of small-cell lung cancer. Curr Oncol Rep 2006 ; 8: 258-264. (Pubitemid 43970977)
80. Peyton JD, Spigel DR, Hainsworth JD, et al. Phase II trial of vinflunine in patients with relapsed small cell lung cancer (abstract 18091). J Clin Oncol 2007 ; 25 (18S). 18091.
81. Cardoso F., Di Leo A., Lohrisch C., et al. Second and subsequent lines of chemotherapy for metastatic breast cancer: What did we learn in the last two decades? Ann Oncol 2002 ; 13: 197-207. (Pubitemid 34704970)
82. Bernard-Marty C., Cardoso F. and Piccart MJ Facts and controversies in systemic treatment of metastatic breast cancer. Oncologist 2004 ; 9: 617-632. (Pubitemid 39546403)
83. Livingston RB, Ellis GK, Gralow JR, et al. Dose-intensive vinorelbine with concurrent granulocyte colony-stimulating factor support in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1997 ; 15: 1395-1400. (Pubitemid 27167371)
84. Calvert H. Pemetrexed (Alimta) a promising new agent for the treatment of breast cancer. Semin Oncol 2003 ; 30: 2-5. (Pubitemid 36506282)
85. Heinemann V. Role of gemcitabine in the treatment of advanced and metastatic breast cancer. Oncology 2003 ; 64: 191-206. (Pubitemid 36438803)
86. Perez EA, Hillman DW, Mailliard JA, et al. Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both. J Clin Oncol 2004 ; 22: 2839-2855.
87. Low JA, Wedam SB, Lee JJ, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J Clin Oncol 2005 ; 23: 2726-2734. (Pubitemid 46179462)
88. Blum JL, Jones SE, Buzdar AU, et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999 ; 17: 485-493. (Pubitemid 29075232)
89. Fumoleau P., Largillier R., Clippe C., et al. Multicentre, phase II study evaluating capecitabine monotherpay in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J Cancer 2004 ; 40: 536-542. (Pubitemid 38220770)
90. Smorenburg CH, Bontenbal M., Seynaeve C., et al. Phase II study of weekly gemcitabine in patients with metastatic breast cancer relapsing or failing both an anthracycline and a taxane. Breast Cancer Res Treat 2001 ; 66: 83-87. (Pubitemid 32397946)
91. Campone M., Cortes-Funes H., Vorobiof D., et al. Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy. Br J Cancer 2006 ; 95 (9). 1161-1166. (Pubitemid 44658478)
92. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987 ; 235: 117-182.
93. Slamon DJ, Godolphin W., Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989 ; 244: 707-712. (Pubitemid 19147683)
94. Hynes NE and Stern DF The biology of erbB-2/neu/ HER-2 and its role in cancer. Biochim Biophys Acta 1994 ; 1198: 165-184.
95. Ravdin PM and Chamness GC The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other marcromolecular markers - a review. Gene 1995 ; 159: 19-27.
96. Vogel CL, Cobleigh MA, Tripathy D., et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002 ; 20: 719-726. (Pubitemid 34111379)
97. Paridaens R., Wildiers H., Dalenc F., et al. Vinflunine in combination with trastuzumab for treatment of HER2-positive metastatic breast cancer (abstract 1058). J Clin Oncol 2007 ; 25: 1020.
98. Yardley D., McCleod M., Rubin M., et al. Final results of a first-line multicenter phase II metastatic breast cancer trial of vinflunine monotherapy and in combination with trastuzumab in HER2+ patients. In: 31st annual San Antonio Breast Cancer symposium, San Antonio, TX, 2008.
99. US National Institutes of Health. Trial of vinflunine plus capecitabine in advanced breast cancer. http://www.clinicaltrials.gov/ct2/show/NCT01095003? term=vinflunine&rank=14 (accessed May 2010 ).
100. Rini B., Vogelzang NJ, Dumas MC, Wadell JL, Taber DA and Stadler WM Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol 2000 ; 18: 2419-2426. (Pubitemid 30415829)
101. Waters JS, Moss C., Pyle L., James M., Hackett S., A'Hern R., et al. Phase II clinical trial of capecitabine and gemcitabine in patients with metastatic renal carcinoma. Br J Cancer 2004 ; 91: 1763-1768. (Pubitemid 39664962)
102. Bladder Cancer Guidelines. Clinical practice guidelines in oncology (version 2.0). J Natl Compr Canc Netw 2007 ; NS - 1.
103. Sternberg CN, Yagoda A., Schar HI, et al. Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. J Urol 1985 ; 133: 403-407. (Pubitemid 15129797)
104. von der Maase H., Hansen SU, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000 ; 18: 3068-3077.
105. Vaughn DJ, Srinivas S., Stadler WM, et al. Phase II study of single-agent vinflunine in platinum-refractory transitional cell carcinoma of the urothelium (TCCU) (abstract 15543). J Clin Oncol 2007 ; 25 (Suppl 18). S653.
106. Petrylak DP, Vaughn DJ, Srinivas S., et al. Phase II study of single-agent vinflunine in platinum-refractory transitional cell carcinoma of the urothelium (TCCU) (abstract 4534). Eur J Cancer 2007 ; (Suppl 5). 309.
107. US National Institutes of Health. Phase III Trial of vinflunine plus best supportive care versus best supportive care in patients with transitional cell carcinoma (TCC) of the urothelial tract. http://clinicaltrials.gov/ct2/show/ NCT00359476?term=vinflunine&rank=13 (accessed February, 2010 ).
108. US National Institutes of Health. First-line treatment of advanced bladder cancer randomized versus. gemcitabine ± vinflunine in patients ineligible to receive cisplatin-based therapy. http://clinicaltrials.gov/ct2/ show/NCT00359476?term=vinflunine&rank=10 (accessed February, 2010 ).
109. Talbot DC, Margery J., Dabouis G., et al. Phase II study of vinflunine in malignant pleural mesothelioma. J Clin Oncol 2007 ; 25 (30). 4751-4756. (Pubitemid 350086477)
110. Lerner HJ, Schoenfeld DA, Martin A., Falkson G. and Borden E. Malignant mesothelioma. The eastern cooperative oncology group (ECOG) experience. Cancer 1983 ; 52: 1981-1985. (Pubitemid 14232234)
111. Zidar BL, Green S., Pierce HI, Roach RW, Balcerzak SP and Militello L. A phase II evaluation of cisplatin in unresectable diffuse malignant mesothelioma: a southwest oncology group study. Invest New Drugs 1988 ; 6: 223-226.
112. Vogelzang NJ, Goutsou M., Corson JM, et al. Carboplatin in malignant mesothelioma: a phase II study of the cancer and leukemia group B. Cancer Chemother Pharmacol 1990 ; 27: 139-142.
113. Steele JP, Shamash J., Evans MT, Gower NH, Tischkowitz MD and Rudd RM Phase II study of vinorelbine in patients with malignant pleural mesothelioma. J Clin Oncol 2000 ; 18: 3912-3917.
114. Vogelzang NJ, Rusthoven JJ, Symanowski J., et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003 ; 21: 2636-2644. (Pubitemid 46606305)
115. Steele JP and Klabatsa A. Chemotherapy options and new advances in malignant pleural mesothelioma. Ann Oncol 2005 ; 16: 345-351. (Pubitemid 40458309)
116. Van Meerbeeck JP, Manegold C., Gaafar R., et al. A randomized phase III study of cisplatin with or without raltirexed in patients with malignant pleural mesothelioma: an intergroup study of the EORTC lung cancer group and NCIC (abstract 7021). J Clin Oncol 2004 ; (Suppl 22). S622.
117. Macdonald DR Neurologic complications of chemotherapy. Neurol Clin 1991 ; 9: 955-967.
118. Quasthoff S. and Hartung HP Chemotherapy-induced peripheral neuropathy. J Neurol 2002 ; 249: 9-17. (Pubitemid 34119018)
119. Hussain M., Wozniak AJ and Edelstein MB Neurotoxicity of antineoplastic agents. Crit Rev Oncol Hematol 1993 ; 14: 61-75. (Pubitemid 23183739)
120. Lobert S., Frankfurter A. and Correia JJ The energetics of vinca alkaloid interactions with tubulin iso-types: implications for drug efficacy and toxicity. Cell Motil Cytoskeleton 1998 ; 39: 107-121. (Pubitemid 28079642)
121. Lobert S., Ingram JW and Correia JJ The thermodynamics of vinca alkaloid-induced tubulin spiral formation. Biophys Chem 2007 ; 126: 50-58. (Pubitemid 46186639)
122. Lobert S., Fahy J., Hill BT, Duflos A., Etievant C. and Correia JJ Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in the leukemic L1210 cell line. Biochemistry 2000 ; 39 (39). 12053-12062.
123. Lobert S., Ingram JW, Hill B., et al. A comparison of thermodynamic parameters for vinorelbine and vinflunine induced tubulin self-association by sedimentation velocity. Mol Pharmacol 1998 ; 53: 908-915. (Pubitemid 28244079)
124. European Medicines Agency. Summary of product characteristics (Javlor). http://www.ema.europa.eu/humandocs/PDFs/EPAR/javlor/emea-combined-h983en.pdf (accessed May 2010 ).
125. US National Institutes of Health. Effect of ketoconazole on the pharmacokinetics of vinflunine. http://clinicaltrials.gov/ct2/show/NCT00388557? term=vinflunine&rank=1 (accessed May 2010 ).
126. US National Institutes of Health. A study of vinflunine in patients with gastric cancer. http://clinicaltrials.gov/ct2/show/NCT00359476?term= vinflunine&rank=9 (accessed May 2010 ).
127. US National Institutes of Health. Vinflunine in hormone refractory prostate cancer (HRPC). http://clinicaltrials.gov/ct2/show/NCT00545766?term= vinflunine&rank=6 (accessed May 2010 ).
128. US National Institutes of Health. A study of the alternative administration of ixabepilone and vinflunine. http://clinicaltrials.gov/ct2/ show/NCT00362830?term=vinflunine&rank=4 (accessed February 2009 ).
129. US National Institutes of Health. Vinflunine and erlotinib or pemetrexed in treating patients with unresectable or metastatic solid tumors. http://clinicaltrials.gov/ct2/show/NCT00362830?term=vinflunine&rank=4 (accessed May 2010 ).