Combination Therapy with Interferon in Renal Cell Carcinoma

  • S. D. Fossa
Conference paper

Abstract

Interferon alpha (IFNα) yields a 15%–20% response rate in patients with metastatic renal cell carcinoma (RCC) when given as monotherapy at doses of 9–18 x 106 U thrice weekly [22]. There seems to be no significant difference in the response rates obtained by different IFNs: IFNα, EFNβ, natural leukocyte IFN, of recombinant IFN. Monotherapy with IFNγ has, however, been insufficiently evaluated in clinical studies. Due to the considerable interstudy variability of the selection criteria of patients treated with IFN, the overall role of this drug in the management of metastatic RCC cannot yet be determined. However, IFN therapy of RCC represents the first treatment of this malignancy which has consistently achieved a response rate of 10% or more. The most frequently responding sites are lung metastases [27]. Treatment should be given for at least 2 months unless the patient progresses before this time interval has elapsed. Patients who after 2 months show an at least 30% reduction have a reasonable chance of finally obtaining an objective response [15]. Responders usually live longer than nonresponders [4, 15], which, however, may mirror a biologically less aggressive disease rather than treatment efficacy.

Keywords

Fatigue Aspirin Radium Oncol Interferon 

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References

  1. 1.
    Aapro MS, Alberts DS, Salmon SE (1983) Interaction of human leukocyte interferon with vincra alkaloids and other chemother apeutic agents against human tumors in clonogenic assay. Cancer Chemother Pharmacol 10: 161–166PubMedCrossRefGoogle Scholar
  2. 2.
    Abdi EA (1988) Combination of interferon and prednisone in human cancer. Eur J Clin Oncol 24: 723–724CrossRefGoogle Scholar
  3. 3.
    Balkwill FR, Moodie EM (1984) Positive interactions between human interferon and cyclophosphamide or adriamycin in a human tumor model system. Cancer Res 44: 904–908PubMedGoogle Scholar
  4. 4.
    Bergerat JP, Herbrecht R, Dufour P, Jocqmin D, Bollack C, Prevot G, Bailly G, de Garis S, Juraschek F, Oberlin F (1988) Combination of recombinant alpha-2A and vinblastine in advanced renal cell cancer. Cancer 62: 2320–2324Google Scholar
  5. 5.
    Cetto GL, Franceschi T, Chiarion-Sileni V, Bellini A, Molino AM, Paccagnella A (1987) Recombinant alpha-2 interferon (EFN) and vinblastine (VBL) in metastatic renal cell carcinoma (MRCC): Phase I-II study. Proc Ecco 4, Abstr no 229Google Scholar
  6. 6.
    Creagan ET, Buckner JC, Hahn RG, Richardson RR, Schaid DJ, Kovach JS (1988) An evaluation of recombinant leukocyte A interferon with aspirin in patients with metastatic renal cell cancer. Cancer 61: 1787–1791PubMedCrossRefGoogle Scholar
  7. 7.
    Mulder P de, Debruyne F, Rikken G, Franssen M, van Hoesel Q, Damsma O (1989) Recombinant) tumor necrosis factor alpha(NFaa) and interferon (IFN)-gamma(g) in the treatment of advanced renal cell carcinoma (RCC). Proc Asco 8: Abstract no 560Google Scholar
  8. 8.
    Dexeus FH, Logothetis CJ, Sella A, Finn L (1989) Interferon alternating with chemo¬therapy for patients with metastatic renal cell carcinoma. Am J Clin Oncol (CCT) 12: 350–354CrossRefGoogle Scholar
  9. 9.
    Diedrich H, Freund M, Schmoll H-J, Wilke H, V Wussow P (1987) Phase II-trial of a combination therapy with vinblastin (VBL), alpha-human-leukocyte-interferon (HU IFN-alpha) and tamoxifen in advanced renal cell carcinoma (RCC). Proc Ecco 4, Abstract no 229Google Scholar
  10. 10.
    Foon K, Doroshow J, Bonnem E, Fefer A, Graham S, Grosh B etal. (1988) A prospective randomized trial of a-2b-interferony-interferon or the combination in advanced metastatic renal cell carcinoma. J Biol Res Mod 7: 540–545Google Scholar
  11. 11.
    Figlin RA, De Kernion JB, Maldazys J, Sarna G (1985) Treatment of renal cell carcinoma with alfa (human leucocyte) interferon and vinblastine combination: A phase I–II trial. Cancer Treat Rep 69: 263–267PubMedGoogle Scholar
  12. 12.
    Fossil SD (1987) Improved subjective tolerability of interferon by combination with prednisolone. Eur J Cancer Clin Oncol 23: 875–876CrossRefGoogle Scholar
  13. 13.
    Fossa SD, De Garis ST (1987) Further experience with recombinant interferon alfa-2α with vinblastine in metastatic renal cell carcinoma: A progress report. Int J Cancer 1: 35–40Google Scholar
  14. 14.
    Fossa SD, Cavalli F, Otto U, Bauer HW, Oberling JM, Achtnich U etal. (1988) Randomized study of roferon-A (IFN) with or without vinblastine (VBL) in advanced or metastatic renal cell cancer (RCC). Proc ASCO 7, 118: Abstract no 453Google Scholar
  15. 15.
    Fossa SD, Raabe N, Moe B (1989) Recombinant interferon-alpha with or without vinblastine in metastatic renal carcinoma. Results of a randomized phase II study. Br J Urol 64: 468–471PubMedCrossRefGoogle Scholar
  16. 16.
    Geboers ADH, de Mulder PHM, Debrayne FMJ, Strijk SP, Damsma O (1988) Alpha and gamma interferon in treatment of advanced renal cell carcinoma. Sem Surg Oncol 4: 191–194Google Scholar
  17. 17.
    Hrusheksy WJ, Murphy GP (1977) Current study of the therapy of advanced renal carcinoma. J Surg Oncol 9: 277CrossRefGoogle Scholar
  18. 18.
    Krigel R, Padavik K, Rudolph A, Comis R (1988) Phase II study of recombinant interleukin-2 (RIL-2) plus recombinant beta interferon (IFN-) in advanced renal cell carcinoma. Proc ASCO 7: Abstract no 509Google Scholar
  19. 19.
    Markowitz A, Talpaz M, Lee K, Parkinson D, Doig R, Rothberg J etal. (1989) Phase I– II study of recombinant interleukin-2 (roil-2) plus recombinant interferon 2A (RlFN-a) in renal cell carcinoma (RCC). Proc ASCO 8: Abstract no 568Google Scholar
  20. 20.
    Miyoshi T, Ogawa S, Kanamori T, Masahiro N, Namba MY (1983) Interferon poten¬tiates cytotoxic effects of 5-fluorouracil on cell proliferation of established human cell lines originating from neoplastic tissues. Cancer Lett 17: 239–247PubMedCrossRefGoogle Scholar
  21. 21.
    Muss HB, Welander C, Caponera M, Reavis K, Cruz JM, Cooper MR etal. (1985) Interferon and doxorubicin in renal cell carcinoma. Cancer Treat Report 69: 721–722Google Scholar
  22. 22.
    Muss HB (1988) The role of biological response modifiers in metatatic renal cell carcinoma. Sem Oncol 15 (Suppl) 5: 30–34Google Scholar
  23. 23.
    Porzolt F, Messerer D, Hautmann R, Gottwald A, Sparwasser H, Stockamp K, Aulitzky W etal. (1988) Treatment of advanced renal cell cancer with recombinant interferon alpha as a single agent and in combination with medroxyprogesterone acetate. A randomized multicenter trial. J Cancer Res Clin Oncol 114: 95–100CrossRefGoogle Scholar
  24. 24.
    Quesada JR, Evans L, Saks SR, Guttermann JU (1988) Recombinant interferon alpha and gamma in combination as treatment for metastatic renal cell carcinoma. J Biol Resp Mod 7: 234–239Google Scholar
  25. 25.
    Rizzo M, Bartoletti R, Selli C, Sicignano A, Criscuolo D (1989) Interferon alpha–2a and vinblastine in the treatment of metastatic renal carcinoma. Eur Urol 16: 271–277PubMedGoogle Scholar
  26. 26.
    Schornagel HJ, Verweij J, ten Bokkel Huinink WW, Klijn JGM, de Mulder PHM, Debrayne FMJ, van Deijk WA etal. (1989) Phase H study of recombinant interferon alpha-2α and vinblastine in advanced renal cell carcinoma. J Urol 142: 253–256PubMedGoogle Scholar
  27. 27.
    Smalley R, Neidhart J, Harris J, Anderson S, Rinehart J, Laszlo J etal. (1989) Pul¬monary metastases from renal cell carcinoma. Proc ASCO 8: Abstract no 508Google Scholar
  28. 28.
    Wadler S, Einzig I, Dutcher JP, Ciobano N, Landau L, Wiernik PH (1988) Phase II trial or recombinant alpha-2b-interferon and low-dose cyclophosphamide in advanced melanoma and renal cell carcinoma. Am J Clin Oncol 11: 55–59PubMedCrossRefGoogle Scholar
  29. 29.
    Welander C, Gaines JT, Homesley HD etal. (1983) In vitro synergistic effects of recombinant human interferon alphaj (rIFN-a2) and doxorubicin on human tumor cell lines. Proc ASCO 2: 42Google Scholar
  30. 30.
    Yamamoto S, Tanaka H, Kanamori T etal. (1983) In vitro studies on potentiation of cytotoxic effects of anticancer drugs by interferon on a human neoplastic cell line (HeLa). Cancer Lett 20: 131–138PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • S. D. Fossa
    • 1
  1. 1.The Norwegian Radium HospitalOslo 3Norway

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