Skip to main content
SpringerLink
Log in

A Phase I Trial of Weekly Gemcitabine and Subcutaneous Interferon Alpha in Patients with Refractory Renal Cell Carcinoma

  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Abstract

Introduction: Recombinant humaninterferon-α2b (rHuIFN-α2b)and Interleukin-2 have limitedeffectiveness in the treatment ofmetastatic renal cell carcinoma (MRCC).Gemcitabine (Gemzar®) is also reported tohave activity against MRCC, and recent invitro, in nude mice xenografts, and humandata suggests increased activity ofgemcitabine (Gemzar®) when combined withIFN-α2b.

Purpose: A phase I clinical trialutilizing gemcitabine (Gemzar®) andrHuIFN-α2b was conducted in patientswith metastatic renal cell carcinoma.

Methods: Treatment consisted of:gemcitabine (Gemzar®) 600 mg/m2 I.V.weekly and rHuIFN-α2b 1.0 MU/m2(dose level A) or 3.0MU/m2 S.C. (doselevel B) three times a week for 6 weekswith a 2 weeks rest period.

Results: Thirteen patients wereentered into the trial and were evaluated.Dose limiting toxicity was predominantlyhematologic, and was seen at dose level B.This included grade 3 anemia (1 patient),neutropenia (1 patient), and nausea (1patient) and grade 4 neutropenia (1patient). The maximal tolerateddose was gemcitabine (Gemzar®)600 mg/m2 I.V. weekly andrHuIFN-α2b 1.0 MU/m2 threetimes a week.

Conclusion: This combination ofgemcitabine (Gemzar®) and rHuIFN-α2bhas significant hematologic toxicitydespite low doses of each agent. Furtherinvestigation of this combination usingthis schedule is not recommended.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics 2000. CA Cancer J Clin 50:7, 2000

    Google Scholar 

  2. Linehan WM, Zbar B, Bates SE, Zelefsky MJ, Yang JC: Cancer of the kidney and ureter. In: DeVita VT, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology. Philadelphia, JB Lippincott Williams & Wilkins Co., 2001

    Google Scholar 

  3. Sandock DS, Seftel AD, Resnick MI: A new protocol for the follow-up of renal cell carcinoma based on pathological stage. J Urol 154:28–31, 1995

    Google Scholar 

  4. Rabinovitch RA, Zelefsky MJ, Gaynor JJ, Fuks Z: Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy. J Clin Oncol 12:206–212, 1994

    Google Scholar 

  5. Golimbu M, Joshi P, Sperber A, Tessler A, Al-Askari S, Morales P: Renal cell carcinoma: Survival and prognostic factors. Urology 27:291–301, 1986

    Google Scholar 

  6. Maldazys JD, DeKernion JB: Prognostic factor in metastatic renal cell carcinoma. J Urol 136:376–379, 1986

    Google Scholar 

  7. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Lovie AC: Results of treatment of 255 patients with metastatic renal cell carcinoma who received high dose recombinant interleukin-2 therapy. J Clin Oncol 13:688–696, 1995

    Google Scholar 

  8. Fisher RJ, Rosenberg SA, Sznol M, Parkinson DR, Fyfe G: High dose aldesleukin in renal cell carcinoma: long term survival update. Cancer J Sci Am 3Suppl. 1:S70–S72, 1997

    Google Scholar 

  9. Bukowski RM. Natural history and therapy of metastatic renal cell carcinoma: role of interleukin 2. Cancer 80:1198–1220, 1997

    Google Scholar 

  10. Proleukin (aldesleukin for injection) package insert. Emeryville (CA): Chiron Therapeutics, 1992

  11. Nanus DM, Pfeffer LM, Bander NH, Bahri S, Albino AP: Antiproliferative and antitumor effects of alpha-interferon in renal cell carcinomas: correlation with the expression of a kidney-associated differentiation glycoprotein. Cancer Res 50:4190–4194, 1990

    Google Scholar 

  12. Minasian LM, Motzer RJ, Gluck L, Mazumar M, Vlamis V, Krown SE: interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol 11:1368–1375, 1993

    Google Scholar 

  13. Fossa SD, Martinelli G, Otto U, Schneider G, Wander H, Oberling F, Baver HW, Achtnicht U, Holdener EE: Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. Ann Oncol 3:301–305, 1992

    Google Scholar 

  14. Neidhart JA, Anderson SA, Harris JE, Rinehart JJ, Lazlo J, Dexus FH, Einhorn LH, Trump DL, Benedetto PW, Tuttle RL: Vinblastine fails to improve response of renal cancer to interferon-alfa: High response rate in patients with pulmonary metastases. J Clin Oncol 9:832–836, 1991

    Google Scholar 

  15. Krown SE: Interferon treatment of renal cell carcinoma: current status and future prospects. Cancer 59:647–651, 1987

    Google Scholar 

  16. Medical Research Council Renal Cancer Collaborators: Interferon-γ and survival in metastatic renal carcinoma: early results of a randomized controlled trial. Lancet 353:14–17, 1999

    Google Scholar 

  17. Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Masseau M, Philip T, Tursz T: Randomized human interleukin-2, recombinant alfa-2a, or both in metastatic renal cell carcinoma. N Engl J Med 338:1272–1278, 1998

    Google Scholar 

  18. DeMulder PHM, Weissbach L, Jakse G, Osieka R, Blatter J: Gemcitabine: atA phase II study in patients with advanced renal cell cancer. Cancer Chemother Pharmacol 37:491–495, 1996

    Google Scholar 

  19. Mertens WC, Eisenhauer EA, Moore M, Venner P, Stewart D, Muldal A, Wong D: Gemcitabine in advanced renal cell carcinoma. Ann Oncol 4:331–332, 1993

    Google Scholar 

  20. Rohde D, Geortz M, Hayn NK, Cremer U, Jakse G: Interferon-2a and gemcitabine (2′,2′-difluorodeoxycytidine) in adult and pediatric renal tumors. Int J Oncol 11:623–627, 1997

    Google Scholar 

  21. Rohde D, Hayn HK, Blatter J, Jakse G: The efficacy of 2′,2′-difluorodeoxycytidine (gemcitabine) combined with interferon in human renal cell carcinoma cell lines. Int J Oncol 12:1361–1366, 1998

    Google Scholar 

  22. Rohde D, Goertz M, Blatter J, Jakse G: The efficacy of 2′2′-difluorodeoxycytidine (gemcitabine) and vinblastine combined with interferon in nude mice xeografts of human renal cell carcinoma. Int J Oncol 12:1367–1372, 1988

    Google Scholar 

  23. Rohde D, Thiemann D, Wildberger J, Wolff J, Jakse G: Treatment of renal cancer patients with gemcitabine (2′2′-difluorodeoxycytidine) and interferons: antitumor activity and toxicity. Oncology Reports 5:1555–1560, 1998

    Google Scholar 

  24. Sella A, Amato RJ, Fitz K: Interferon-alpha and 5-fluourouracil combination chemotherapy for metastatic renal cell cancer. Interferons Cytokines 1:17–21, 1992

    Google Scholar 

  25. Sparano JA, Wadler S, Diasio RB, Zhang R, Lu Z, Schwartz EL, Einzig A, Wiernik PH: Phase I trial of low-dose, prolonged continuous infusion fluorouracil plus interferon-alfa: Evidence for enhanced fluourouracil toxicity without pharmacokinetic perturbation. J Clin Oncol 11:1609–1617, 1993

    Google Scholar 

  26. Wadler S, Lembersky B, Atkins M, Kirkwood J, Petrelli N: Phase II trial of fluorouracil and recombinant alfa-2a interferon in patients with advanced colorectal carcinoma: An Eastern Cooperative Oncology Group study. J Clin Oncol 9:1806–1810, 1991

    Google Scholar 

  27. Haarstad H, Jacobsen AB, Schjølseth SA, Risberg T, Fossa SD: Interferon-alfa, 5-FU and prednisone in metastatic renal cell carcinoma: A phase II study. Ann Oncol 5:245–248, 1994

    Google Scholar 

  28. Bukowski R: Cytokine combinations: Therapeutic use in patients with advanced renal cell carcinoma. Semin Oncol 27:204–212, 2000

    Google Scholar 

  29. Pittman K, Selby P: The management of renal cell carcinoma. Crit Rev Oncol Hematol 16:181–200, 1994

    Google Scholar 

  30. Fuxius S, Mross K, Mansouri K, Unger C: Phase I study with gemcitabine and interferon alfa-2b in patients with advanced ovarian, pancreatic, kidney and NSCL cancer. Proc Am Soc Clin Oncol 18:211a (Abstr), 1999

    Google Scholar 

  31. Abbruzzese JL, Grunewald R, Weeks EA, Gravel D, Adams T, Nowak B, Mineishi S, Tarassoff P, Satterlee W, Raber MN: A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol 9:491–498, 1991

    Google Scholar 

  32. Pollera CF, Ceribelli A, Crecco M, Calabresi F: Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study. Invest New Drugs 12:111–119, 1994.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, USA

    F. Perez-Zincer, T. Olencki, G.T. Budd, D. Peereboom & R.M. Bukowski

  2. Experimental Therapeutics Program, Cleveland Clinic Foundation, Taussig Cancer Center, Cleveland, OH, USA

    T. Olencki, G.T. Budd, D. Peereboom, P. Elson & R.M. Bukowski

Authors
  1. F. Perez-Zincer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Olencki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G.T. Budd
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Peereboom
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Elson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R.M. Bukowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perez-Zincer, F., Olencki, T., Budd, G. et al. A Phase I Trial of Weekly Gemcitabine and Subcutaneous Interferon Alpha in Patients with Refractory Renal Cell Carcinoma. Invest New Drugs 20, 305–310 (2002). https://doi.org/10.1023/A:1016214030069

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1016214030069

Search

Navigation