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Overview of preclinical and clinical studies of interferon alfa-2b in combination with cytotoxic drugs

  • Papers Presented at a Symposium on Interferons in Oncology, Budapest, 26th August, 1986
  • Published:
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Summary

Both in vitro and in vivo studies have demonstrated antiproliferative effects of interferon alfa-2b (Intron A; Schering-Plough) when tested with human tumor cells. A clonogenic assay has been widely used to determine its direct antiproliferative effects on human tumor cells in vitro using colony reduction as a reproducible endpoint. As a single agent, interferon alfa-2b shows maximum tumor cell colony reduction when used in high concentrations with continuous cell exposure. Short-term exposure to interferon alfa-2b does not produce significant tumor cell colony reduction. Clonogenic assays have also been used to test combinations of interferon alfa-2b with cytotoxic drugs. Variations in drug scheduling, sequencing and concentrations have indicated the best combinations which maximize tumor cell colony reduction. Combinations of interferon alfa-2b with doxorubicin, cisplatin, vinblastine, melphalan and cyclophosphamide have been shown to have at least additive and occasionally synergistic antiproliferative effects.

In clinical trials, optimal pairs of agents have been identified frequently combining either doxorubicin, cisplatin or vinblastine with interferon alfa-2b. Pretreatment with interferon alfa-2b has been adopted from in vitro studies and applied to most clinical trials. One study has enrolled 135 patients having a variety of advanced or recurrent solid tumor types, using a schema which combines interferon alfa-2b and doxorubicin administration, both given on a weekly basis for three weeks, followed by treatments every two weeks in responding patients. Clinical responses have been seen using this regimen in patients with ovarian, cervical, colorectal and pancreatic carcinomas and in one lymphoma patient. Another study has been designed combining melphalan, prednisone and interferon alfa-2b for the treatment of patients with relapsing multiple myeloma. This is also based upon preclinical data.

New methods of administration are being studied giving interferon alfa-2b as a single agent or in combination with cisplatin by the intraperitoneal route to patients with relapsing ovarian carcinomas limited to the peritoneal cavity. This method can maximize both the levels of interferon alfa-2b as well as the tumor cell exposure time.

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References

  1. Ratain MJ, Golomb HM, Vardiman JW: Treatment of hairy cell leukemia with recombinant alpha2 interferon. Blood 65:644–648, 1985

    Google Scholar 

  2. O'Connell MJ, Colgan JP, Oken MM: Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hodgkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study. J Clin Oncol 4:128–136, 1986

    Google Scholar 

  3. Volberding PA, Wofsy CB, Abrams DI: Interferon and interleukin-2 therapy of Kaposi's sarcoma. Adv Exp Med Biol 187:151–157, 1985

    Google Scholar 

  4. Costanzi JJ, Cooper MR, Scarffe JH: Phase II study of recombinant alpha-2 interferon in resistant multiple myeloma. J Clin Oncol 3:654–659, 1985

    Google Scholar 

  5. Kirkwood JM, Ernstoff M: Interferons in the treatment of human cancer. J Clin Oncol 2(4):336–352, 1984

    Google Scholar 

  6. Welander CE, Morgan TM, Homesley HD, Trotta PP, Spiegel RJ: Combined recombinant human interferon alpha2 and cytotoxic agents studied in the clonogenic assay. Int J Cancer 35:721–729, 1985

    Google Scholar 

  7. Saito T, Berens ME, Welander CE: Direct and indirect effects of human recombinant α-interferon on tumor cells in a clonogenic assay. Cancer Res 46:1142–1147, 1986

    Google Scholar 

  8. Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 197:461–463, 1977

    Google Scholar 

  9. Pattillo RA, Hussa RO, Story MT, Ruckert ACF, Shalaby MR, Mattling RF: Tumor antigen and human chorionic gonadotropin in Caski cells: A new epidermoid cervical cancer cell line. Science 196:1456–1458, 1977

    Google Scholar 

  10. Fogh J, Trempe G: New human tumor cells lines. In J Fogh (ed): Human Tumor Cells in Vitro. Plenum Press, New York, pp 115–159, 1975

    Google Scholar 

  11. Soule HD, Vasquez J, Long A, Albert S, Brennan M: A human cell line from a pleural effusion derived from a breast carcinoma. J Nat Cancer Inst 51:1409–1416, 1973

    Google Scholar 

  12. Carey T, Takahsahi T, Resnick LA, Oettgen HF, Old LJ: Cell surface antigens of human malignant melanoma: Mixed hemadsorption assays for humoral immunity to cultural autologous melanoma cells. Proc Nat Acad Sci USA 73:3278–3282, 1976

    Google Scholar 

  13. Saito T: Personal communication

  14. Momparler RL: In vitro systems for evaluation of combination chemotherapy. Pharmacol Therapeutics 8:21–35, 1980

    Google Scholar 

  15. Drewinko TL, Loo B, Brown B, Gottlieb JA, Freireich EJ: Combination chemotherapy in vitro with Adriamycin. Observations of additive, antagonistic and synergistic effects when used in the drug combinations of cultured human lymphoma cells. Cancer Biochem Biophys 1:187–195, 1976

    Google Scholar 

  16. Matsuoka Y, Moore GE, Yagi Y: Production of free light chains of immunoglobin by a hematopoietic cell line derived from a patient with multiple myeloma. Proc Soc Exp Biol Med 125:1246–1250, 1967

    Google Scholar 

  17. Aapro MS, Alberts DS, Salmon SE: Interaction of human leukocyte interferon with vinca alkaloids and other chemotherapeutic agents against human tumors in clonogenic assay. Cancer Chemother Pharmacol 10:161–166, 1983

    Google Scholar 

  18. Miyoshi T, Ogawa S, Kanamori T: Interferon potentiates cytotoxic effects of 5-fluorouracil on cell proliferation of established human cell lines originating from neoplastic tissues. Cancer Letters 17:239–247, 1983

    Google Scholar 

  19. Balkwill FR, Moodie EM: Positive interaction between human interferon and cyclophosphamide or Adriamycin in a human tumor model system. Cancer Res 44:904–908, 1984

    Google Scholar 

  20. Gresser I, Maury C, Tovey M: Efficacy of combined interferon cyclophosphamide therapy after diagnosis of lymphoma in AKR mice. Eur J Cancer 14:97–99, 1978

    Google Scholar 

  21. Slater LM, Wetzel MW, Cesario T: Combined interferon-antimetabolite therapy of murine L1210 leukemia. Cancer 48:5–9, 1981

    Google Scholar 

  22. Welander CE, Muss HB, Homesley HD, Spiegel RJ: Phase II trial of combined human interferon alpha-2 and doxorubicin in advanced solid tumors (Abstract). Proc Am Soc Clin Oncol 4:220, 1985

    Google Scholar 

  23. Sarosy GA, Brown TD, Von Hoff DD, Spiegel RJ, Golando JP, Beougher KL, Kohn JG, Kisner DL: Phase I study of α2-interferon plus doxorubicin in patients with solid tumors. Cancer Res 46:5368–5371, 1986

    Google Scholar 

  24. Welander CE, Berens ME, Cooper MR: Combined antiproliferative effects of interferon alfa-2b (Intron AR) plus melphalan and prednisone in human myeloma. Submitted for publication

  25. Cooper MR, Fefer A, Thompson, J: Alpha-2 interferon/ melphalan/prednisone in previously untreated patients with multiple myeloma: A phase II trial. Cancer Treat Rep 70:473–476, 1986

    Google Scholar 

  26. De Kernion JB, Sarna GP, Figlin RA: The treatment of renal cell carcinoma with leukocyte alpha interferon. J Urol 130:1063–1066, 1983

    Google Scholar 

  27. Hrushesky WJ, Murphy GP: Current status of the therapy of advanced renal carcinoma. J Surg Oncol 19:277–288, 1977

    Google Scholar 

  28. Figlin RA, De Kernion JB, Maldazys J: Treatment of renal cell carcinoma with (human leukocyte) interferon and vinblastine in combination: A phase II trial. Cancer Treat Rep 69:263–267, 1986

    Google Scholar 

  29. Creagan ET, Kovach JS, Long HJ, Richardson RL: Phase I study of recombinant leukocyte A human interferon combined with BCNU in selected patients with advanced cancer. J Clin Oncol 4:408–413, 1986

    Google Scholar 

  30. Berek JS, Hacker NF, Lichtenstein A: Intraperitoneal recombinant α-interferon for “salvage” immunotherapy in stage III epithelial ovarian cancer: A Gynecology Oncology Group study. Cancer Res 45:4447–4453, 1985

    Google Scholar 

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  1. Section on Gynecologic Oncology, Bowman Gray School of Medicine, Winston-Salem, NC, USA

    Charles E. Welander

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  1. Charles E. Welander
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Welander, C.E. Overview of preclinical and clinical studies of interferon alfa-2b in combination with cytotoxic drugs. Invest New Drugs 5 (Suppl 4), S47–S59 (1987). https://doi.org/10.1007/BF00207263

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  • DOI: https://doi.org/10.1007/BF00207263

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