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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Dec;83(12):1612–1616. doi: 10.1054/bjoc.2000.1480

Evidence for a schedule-dependent deleterious interaction between paclitaxel, vinblastine and cisplatin (PVC) in the treatment of advanced transitional cell carcinoma

C Mulatero 1, B R McClaren 1, M Mason 2, R T D Oliver 1, C J Gallagher 1
PMCID: PMC2363438  PMID: 11104554

Abstract

A phase II study to evaluate the efficacy and toxicity of the combination of vinblastine, paclitaxel and cisplatin (PVC) in previously untreated patients with advanced transitional cell carcinoma. Chemotherapy naive patients with locally advanced or metastatic transitional cell carcinoma received the intravenous combination of paclitaxel 175 mg/m2 over three hours followed by cisplatin 70 mg/m2 over 3 hours on day 1 and vinblastine 3 mg/m2 as a bolus on days 1 and 8 on a 21-day cycle, to a maximum of 6 cycles. The day 8 vinblastine was omitted if the total neutrophil count was <1.0. 15 patients (13 M, 2 F) of median age 66 (54–75) received a median of 5 cycles of treatment. There were two complete responses (13%; 95% CI 2–40%) and five partial responses (33%; 95% CI 12–62%), for an overall response rate of 46% (95% CI 21–73%). Responses occurred only in those with locally recurrent tumours and/or lymph nodes involved. Neutropenia at Grade 3–4 occurred in 14 of 67 cycles (21%) resulting in 7 episodes of neutropenic sepsis. Grade 3–4 thrombocytopenia was not observed. Other Grade 3 toxicity included alopecia (10 pts), diarrhoea (2 pts), constipation resulting in bowel obstruction (2 pts), nephrotoxicity (1 pt), myalgic pain (1 pt) and peripheral neuropathy (1 pt). Six patients developed Grade 2 paraesthesia. The median time to progression was 6 months and the median survival was 11 months. The regimen PVC was both less effective against transitional cell carcinoma and less toxic than expected. This may reflect an inhibitory interaction between vinblastine and paclitaxel and this schedule cannot be recommended for further investigation. © 2000 Cancer Research Campaign http://www.bjcancer.com

Keywords: transitional cell, paclitaxel, vinblastine, cisplatin, schedule

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Selected References

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  1. Bajorin D. F., McCaffrey J. A., Hilton S., Mazumdar M., Kelly W. K., Scher H. I., Spicer J., Herr H., Higgins G. Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial. J Clin Oncol. 1998 Aug;16(8):2722–2727. doi: 10.1200/JCO.1998.16.8.2722. [DOI] [PubMed] [Google Scholar]
  2. Blumenreich M. S., Yagoda A., Natale R. B., Watson R. C. Phase II trial of vinblastine sulfate for metastatic urothelial tract tumors. Cancer. 1982 Aug 1;50(3):435–438. doi: 10.1002/1097-0142(19820801)50:3<435::aid-cncr2820500309>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  3. Boshoff C., Oliver R. T., Gallagher C. J., Ong J. Accelerated cisplatin-based chemotherapy for advanced bladder cancer. Eur J Cancer. 1995 Sep;31A(10):1633–1636. doi: 10.1016/0959-8049(95)00201-s. [DOI] [PubMed] [Google Scholar]
  4. Giannakakou P., Villalba L., Li H., Poruchynsky M., Fojo T. Combinations of paclitaxel and vinblastine and their effects on tubulin polymerization and cellular cytotoxicity: characterization of a synergistic schedule. Int J Cancer. 1998 Jan 5;75(1):57–63. doi: 10.1002/(sici)1097-0215(19980105)75:1<57::aid-ijc10>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  5. Harker W. G., Meyers F. J., Freiha F. S., Palmer J. M., Shortliffe L. D., Hannigan J. F., McWhirter K. M., Torti F. M. Cisplatin, methotrexate, and vinblastine (CMV): an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study. J Clin Oncol. 1985 Nov;3(11):1463–1470. doi: 10.1200/JCO.1985.3.11.1463. [DOI] [PubMed] [Google Scholar]
  6. Hayward J. L., Carbone P. P., Heusen J. C., Kumaoka S., Segaloff A., Rubens R. D. Assessment of response to therapy in advanced breast cancer. Br J Cancer. 1977 Mar;35(3):292–298. doi: 10.1038/bjc.1977.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Herr H. W. Cis-diamminedichloride platinum II in the treatment of advanced bladder cancer. J Urol. 1980 Jun;123(6):853–855. doi: 10.1016/s0022-5347(17)56161-3. [DOI] [PubMed] [Google Scholar]
  8. Jekunen A. P., Christen R. D., Shalinsky D. R., Howell S. B. Synergistic interaction between cisplatin and taxol in human ovarian carcinoma cells in vitro. Br J Cancer. 1994 Feb;69(2):299–306. doi: 10.1038/bjc.1994.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Loehrer P. J., Sr, Einhorn L. H., Elson P. J., Crawford E. D., Kuebler P., Tannock I., Raghavan D., Stuart-Harris R., Sarosdy M. F., Lowe B. A. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992 Jul;10(7):1066–1073. doi: 10.1200/JCO.1992.10.7.1066. [DOI] [PubMed] [Google Scholar]
  10. Merrin C. Treatment of advanced bladder cancer with cis-diamminedichloroplatinum (II NSC 119875): a pilot study. J Urol. 1978 Apr;119(4):493–495. doi: 10.1016/s0022-5347(17)57527-8. [DOI] [PubMed] [Google Scholar]
  11. Natale R. B., Yagoda A., Watson R. C., Whitmore W. F., Blumenreich M., Braun D. W., Jr Methotrexate: an active drug in bladder cancer. Cancer. 1981 Mar 15;47(6):1246–1250. doi: 10.1002/1097-0142(19810315)47:6<1246::aid-cncr2820470603>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  12. Oliver R. T., England H. R., Risdon R. A., Blandy J. P. Methotrexate in the treatment of metastatic and recurrent primary transitional cell carcinoma. J Urol. 1984 Mar;131(3):483–485. doi: 10.1016/s0022-5347(17)50459-0. [DOI] [PubMed] [Google Scholar]
  13. Oliver R. T., Newlands E. S., Wiltshaw E., Malpas J. S. A phase 2 study of Cis-platinum in patients with recurrent bladder carcinoma. The London and Oxford Co-operative Urological Cancer Group. Br J Urol. 1981 Oct;53(5):444–447. doi: 10.1111/j.1464-410x.1981.tb03227.x. [DOI] [PubMed] [Google Scholar]
  14. Papamichael D., Gallagher C. J., Oliver R. T., Johnson P. W., Waxman J. Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter. Br J Cancer. 1997;75(4):606–607. doi: 10.1038/bjc.1997.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Parker S. L., Tong T., Bolden S., Wingo P. A. Cancer statistics, 1997. CA Cancer J Clin. 1997 Jan-Feb;47(1):5–27. doi: 10.3322/canjclin.47.1.5. [DOI] [PubMed] [Google Scholar]
  16. Peters P. C., O'Neill M. R. Cis-diamminedichloroplatinum as a therapeutic agent in metastatic transitional cell carcinoma. J Urol. 1980 Mar;123(3):375–377. doi: 10.1016/s0022-5347(17)55943-1. [DOI] [PubMed] [Google Scholar]
  17. Rossof A. H., Coltman C. A., Jr, Jones S. E., Talley R. W. Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1605–1608. [PubMed] [Google Scholar]
  18. Roth B. J., Dreicer R., Einhorn L. H., Neuberg D., Johnson D. H., Smith J. L., Hudes G. R., Schultz S. M., Loehrer P. J. Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 1994 Nov;12(11):2264–2270. doi: 10.1200/JCO.1994.12.11.2264. [DOI] [PubMed] [Google Scholar]
  19. Rowinsky E. K., Citardi M. J., Noe D. A., Donehower R. C. Sequence-dependent cytotoxic effects due to combinations of cisplatin and the antimicrotubule agents taxol and vincristine. J Cancer Res Clin Oncol. 1993;119(12):727–733. doi: 10.1007/BF01195344. [DOI] [PubMed] [Google Scholar]
  20. Sternberg C. N., Yagoda A., Scher H. I., Watson R. C., Ahmed T., Weiselberg L. R., Geller N., Hollander P. S., Herr H. W., Sogani P. C. Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. J Urol. 1985 Mar;133(3):403–407. doi: 10.1016/s0022-5347(17)48996-8. [DOI] [PubMed] [Google Scholar]
  21. Tu S. M., Hossan E., Amato R., Kilbourn R., Logothetis C. J. Paclitaxel, cisplatin and methotrexate combination chemotherapy is active in the treatment of refractory urothelial malignancies. J Urol. 1995 Nov;154(5):1719–1722. [PubMed] [Google Scholar]
  22. Yagoda A. Chemotherapy of urothelial tract tumors. Cancer. 1987 Aug 1;60(3 Suppl):574–585. doi: 10.1002/1097-0142(19870801)60:3+<574::aid-cncr2820601524>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  23. Yagoda A., Watson R. C., Gonzalez-Vitale J. C., Grabstald H., Whitmore W. F. Cis-dichlorodiammineplatinum(II) in advanced bladder cancer. Cancer Treat Rep. 1976 Jul;60(7):917–923. [PubMed] [Google Scholar]
  24. Yagoda A., Watson R. C., Whitmore W. F., Grabstald H., Middleman M. P., Krakoff I. H. Adriamycin in advanced urinary tract cancer: experience in 42 patients and review of the literature. Cancer. 1977 Jan;39(1):279–285. doi: 10.1002/1097-0142(197701)39:1<279::aid-cncr2820390143>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]

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