Investigational New Drugs

, Volume 24, Issue 5, pp 429–434 | Cite as

Phase II study of vinflunine in patients with metastatic renal cell carcinoma

  • D. Goldstein
  • S. P. Ackland
  • D. R. Bell
  • I. N. Olver
  • I. D. Davis
  • M. A. Rosenthal
  • G. C. Toner
  • M. C. Pinel
  • M. Byrne
Phase II Studies

Summary

Purpose: An open-label, multicentre, non-comparative phase II trial to determine the response rate of intravenous vinflunine as first line chemotherapy in patients with metastatic renal cell carcinoma (RCC). Patients and methods: Patients with metastatic RCC were treated with vinflunine 350 mg/m2 (n = 11) or 320 mg/m2 (n = 22) administered intravenously every 21 days. Results: Out of 33 patients included in this study, one partial response was observed in the group treated at 350 mg/m2 and none in the group receiving 320 mg/m2 resulting in a response rate in this population of 9.1% (95% CI: 0.2–41.3). Median progression free survival was 5.6 months (95% CI: 2.8–14.4) for patients treated at 350 mg/m2, and 3.3 months (95% CI: 1.6–6.4) for those treated at 320 mg/m2.The median survival time was 10.4 months (95% CI: 6.8–12.4) for the whole study population. The principal toxicities were grade 3/4 neutropaenia —90.9% at 350 mg/m2 and 68.1% at 320 mg/m2, febrile neutropaenia was recorded in 3 patients (27.3%) at 350 mg/m2 and in 5 patients (22.7%) at 320 mg/m2. One episode of thromboembolic event was reported in 1 patient at each dose level. Conclusion: Vinflunine given intravenously once every 3 weeks has not shown any clinically relevant activity in the management of patients with metastatic renal cell carcinoma; tolerance of the treatment was better at a dose of 320 mg/m2 than at 350 mg/m2.

Keywords

Vinflunine Renal cell carcinoma 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Motzer RJ, Russo P (2000) Systemic therapy for renal cell carcinoma. J Urol 163:408–417PubMedCrossRefGoogle Scholar
  2. 2.
    Motzer RJ, Mazumdar M, Bacik J, Russo P, Berg WJ, Metz EM (2000) Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma. J Clin Oncol 18:1928–1935PubMedGoogle Scholar
  3. 3.
    Yang JC, Haworth L, Sherry RM, et al (2003) A randomised trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434PubMedCrossRefGoogle Scholar
  4. 4.
    Motzer RJ, Rini BI, Michaelson MD, Redman BG, Hudes GR, Wilding G, Bukowski RM, George DJ, Kim ST, Baum CM (2005) Phase 2 trials of SU11248 show antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 23:4508Google Scholar
  5. 5.
    Escudier B, Szczylik C, Eisen T, Stadler WM, Schwartz B, Shan M, Bukowski RM (2005) Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 23:LBA4510Google Scholar
  6. 6.
    Pyrhönen S, Salminen E, Lehtonen T, et al. (1999) Prospective randomized trial of interferon alpha-2a plus vinblastine versus vinblastine alone in patients with advanced renal cancer. J Clin Oncol 17:2859–2867PubMedGoogle Scholar
  7. 7.
    Hill BT, Fiebig HH, Waud WR, et al. (1999) Superior in vivo experimental antitumour activity of vinflunine, relative to vinorelbine, in a panel of human tumour xenografts. Eur J Cancer 35:512–520PubMedCrossRefGoogle Scholar
  8. 8.
    Bennouna J, Fumoleau P, Armand J-P, Raymond E, Campone M, Delgado F-M, Puozzo C, Marty M (2003) 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 14:630–637PubMedCrossRefGoogle Scholar
  9. 9.
    Green S, Weiss GR (1992) Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Investigational New Drugs 10:239–253PubMedCrossRefGoogle Scholar
  10. 10.
    WHO Handbook for reporting results for cancer treatment, Geneva: World Health Organisation, 1979Google Scholar
  11. 11.
    Fleming TR (1982) One-sample multiple testing procedure for phase II clinical trials. Biometrics 38:143–151PubMedGoogle Scholar
  12. 12.
    Weber BL, Vogel C, Jones S, et al. (1995) Intravenous vinorelbine as first line and second line therapy in advanced breast cancer. J Clin Oncol 13:2722–2730PubMedGoogle Scholar
  13. 13.
    Rini B, Vogelzang NJ, Dumas MC, Wadell JL, Taber DA, Stadler WM (2000) Phase II trial of weekly intravenous gemcitabine with continuous infusion fluororuracil in patients with metastatic renal cell cancer. J Clin Oncol 18:2419–2426PubMedGoogle Scholar
  14. 14.
    Waters JS, Moss C, Pyle L, James M, Hackett S, A’Hern R, Gore M, Eisen T (2004) Phase II clinical trial of capecitabine and gemcitabine in patients with metastatic renal carcinoma. Br J Cancer 91:1763–1768PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • D. Goldstein
    • 1
  • S. P. Ackland
    • 2
  • D. R. Bell
    • 3
  • I. N. Olver
    • 4
  • I. D. Davis
    • 5
  • M. A. Rosenthal
    • 6
  • G. C. Toner
    • 7
  • M. C. Pinel
    • 8
  • M. Byrne
    • 9
  1. 1.Prince of Wales HospitalRandwickAustralia
  2. 2.Mater Misericordiae HospitalWaratahAustralia
  3. 3.Royal North Shore HospitalSt. LeonardsAustralia
  4. 4.Royal Adelaide HospitalAdelaideAustralia
  5. 5.Austin HealthHeidelbergAustralia
  6. 6.Royal Melbourne HospitalParkvilleAustralia
  7. 7.Peter Mac Callum Cancer CentreEast MelbourneAustralia
  8. 8.Institut de Recherche Pierre FabreBoulogne BillancourtFrance
  9. 9.Sir Charles Gairdner HospitalNedlandsAustralia

Personalised recommendations