Skip to main content

Advertisement

SpringerLink
Log in

A phase II study of combined administration of dacarbazine and carboplatin with home therapy of recombinant interleukin-2 and interferon-α2a in patients with advanced malignant melanoma

  • Original Articles
  • Metastatic Malignant Melanoma, Chemotherapy, Immunotherapy, Recombinant Interferon, Interleikin-2, Carboplatin, Dacarbazine
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Chemotherapy and interleukin-2 (IL-2) and/or interferon α (IFNα) produce objective responses in a proportion of patients with advanced malignant melanoma. The duration of response to chemotherapy is usually less than 4 months, and immunotherapy has resulted in longlasting remissions in a small number of patients with metastatic melanoma. The current study was conducted to improve the antitumor efficacy and the interactions between recombinant (r) IL-2, rIFNα2a and chemotherapy. A total of 16 evaluable patients with metastatic malignant melanoma were entered into a phase-II study designed to assess the response rate and therapeutic efficacy of dacarbazine and carboplatin followed by rIL-2 and rIFNα2a. Patients received 750 mg/m2 dacarbazine with 400 mg/m2 carboplatin each by intravenous bolus on days 1 and 22. Recombinant IL-2 and IFNα2a were administered on an outpatient basis (home therapy) subcutaneously for 6 consecutive weeks: 4.8×106 IU/m2 rIL-2 daily, 5 days a week; 6.0×106 IU/m2 rIFNα2a thrice weekly. There were responses in 6 of the 16 enrolled patients with an overall response rate of 37.5% (95% confidence interval: 14%–61%). All responding patients had partial responses. The median survival time of the responding patients was significantly better than that of patients with progressive and stable disease (P=0.03). The median duration of response was 11 months (range 2–24 months). Responses in lung, liver, soft tissue and lymph-node sites were noted.

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. Atzpodien J, Kirchner H (1990) Cancer, cytokines and cytotoxic cells: interleukin-2 in the immunotherapy of human neoplasms. Klin Wochenschr 68: 1

    Google Scholar 

  2. Atzpodien J, Krofer A, Evers P, Franks CR, Knuver-Hopf J, Fischer M, Mohr H, Dallmann I, Hadam M, Poliwoda H., Kirchner H (1990) Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy. A phase II outpatient study. Mol Biother 2: 18

    PubMed  Google Scholar 

  3. Atzpodien J, Korfer A, Franks CR, Poliwoda H, Kirchner H (1990) Home therapy with recombinant interleukin-2 and interferon-α2b in advanced human malignancies. Lancet 335: 1509

    PubMed  Google Scholar 

  4. Chang A, Hunt M, Parkinson DR, Hochster H, Smith TJ (1993) Phase II trial of carboplatin in patients with metastatic malignant melanoma. A report from the Eastern Cooperative Oncology Group. Am J Clin Oncol 16: 152

    PubMed  Google Scholar 

  5. Coates A, Rallings M, Hersey P, Swanson C (1986) Phase II study of recombinant alpha-2 interferon in advanced malignant melanoma. J Interferon Res 6: 1

    Google Scholar 

  6. Creagan ET, Ahamann DL, Green SG, Long HG, Frytak S, O'Fullon JR, Itri LM (1984) Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma. J Clin Oncol 2: 1002

    PubMed  Google Scholar 

  7. Eisenthal A, Skornick Y, Ron I, Zakuth V, Chaitchik S (1993) Phenotypic and functional profile of peripheral blood mononuclear cells isolated from melanoma patients undergoing combined immunotherapy and chemotherapy. Cancer Immunol Immunother 37: 367

    PubMed  Google Scholar 

  8. Evans LM, Casper ES, Rosenbluth R (1987) Phase II trial of carboplatin in advanced malignant melanoma. Cancer Treat Rep 71:171

    PubMed  Google Scholar 

  9. Falkson CI, Falkson G, Falkson HC (1991) Improved results with addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J Clin Oncol 9: 1403

    PubMed  Google Scholar 

  10. Flaherty LE, Redman BG, Chabot GG, Martino S, Gualdoni SM, Heilbrun LK, Valdivieso M, Bradley EC (1990) A phase II study of dacarbazine in combination with outpatient interleukin-2 in metastatic malignant melanoma. Cancer 65: 2471

    PubMed  Google Scholar 

  11. Flaherty LE, Robinson W, Redman BG, Gonzalez R, Martino S, Kraut M, Valdivieso M, Rudolph AR (1993) A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatif malignant melanoma. Cancer. 71: 3520

    PubMed  Google Scholar 

  12. Fletcher J, Dana B, Jewell W, Townsend R, Fletcher W (1986) Evaluation of cisplatin and DTIC combination chemotherapy in disseminated melanoma: a SWOG phase II pilot study. Proc Am Soc Clin Oncol 5: 131

    Google Scholar 

  13. Goodnight JE, Moseley HS, Eilber FR, Sarna G, Morton DL (1979) Cis-dichlorodiammine-platinum (II) alone and combined with DTIC for treatment of disseminated malignant melanoma. Cancer Treat Rep 63: 2005

    PubMed  Google Scholar 

  14. Gracomini P, Aguzzi A, Pestka S, Fisher PB, Ferrone S (1984) Modulation by recombinant DNA leukocyte (alpha) and fibroblast (beta) interferons by the expression and shedding of HLA- and tumor-associated antigens by human melanoma cells. J Immunol 133: 1649

    PubMed  Google Scholar 

  15. Gresser I (1977) Commentary on varied biologic effects of interferon. Cell Immunol 34: 406

    PubMed  Google Scholar 

  16. Hersey P, Hasic E, MacDonal M, Edwards A, Spurling A, Coates AS, Milton GW, McCarthy WH (1985) Effects of recombinant leukocyte interferon (r-IFN alpha A) on tumor growth and immune responses in patients with metastatic melanoma. Br J Cancer 51: 815

    PubMed  Google Scholar 

  17. Hersey P, McLeod GRC, Thomson DB (1991) Treatment of advanced malignant melanoma with rIFNα in combination with DTIC. Br J Haematol 79: 60

    PubMed  Google Scholar 

  18. Huberman M, Bering H, Fallon B, Tessitore J, Sonnenborn H, Paul S, Zeffren J, Levitt D, Groopman J (1991) A Phase I study of an outpatient regimen of recombinant human interleukin-2 and alfa-2a-interferon in patients with solid tumors. Cancer 68: 1708

    PubMed  Google Scholar 

  19. Icli F, Karaguz H (1991) Treatment of metastatic malignant melanoma with 24 hours of continuous venous infusion of DTIC and cisplatin. J Surg Oncol 48: 199

    PubMed  Google Scholar 

  20. Khavat D, Borel C, Antonie F, Benhamouda A, Soubrane CI, Auclerc G, Franks C, Weil M, Vuillemin E, Banzet P (1992) Highly active chemoimmunotherapy (cisplatin, IL-2, IFN-α) in the treatment of metastatic malignant melanoma. Proc ASCO 11: 332

    Google Scholar 

  21. Lee RE, Lotze MT, Skibber JM, Tucker E, Bonow RO, Ognibene FP, Carrasquillo JA, Shelhamer JH, Parrillo JE, Rosenberg SA (1989) Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol 7: 7

    PubMed  Google Scholar 

  22. Legha SS (1986) Interferons in the treatment of malignant melanoma, A review of recent trials. Cancer 57: 1675

    PubMed  Google Scholar 

  23. Legha SS (1989) Current therapy for malignant melanoma. Semin Oncol 16: 34

    Google Scholar 

  24. McLeod GRC, Thomson DB, Hersey P (1987) rIFNα2a in advanced malignant melanoma, a phase I–II study in combination with DTIC. Int J Cancer 1 [Suppl]: 31

    Google Scholar 

  25. Oratz R, Speyer JL, Green M, Blum R, Wernz JC, Muggin FM (1987) Treatment of metastatic malignant melanoma with dacarbazine and cisplatin. Cancer Treat Rep 71: 877

    PubMed  Google Scholar 

  26. Parkinson DR (1988) Interleukin-2 in cancer therapy. Semin Oncol 15: 10

    Google Scholar 

  27. Prichard KI, Quirt IC, Cowan DH, Osoba D, Kutas GJ (1980) DTIC therapy in metastatic malignant melanoma: a simplified dose schedule. Cancer Treat Rep 64: 1123

    PubMed  Google Scholar 

  28. Ron IG, Inbar MJ, Gutman M, Merimsky O, Chaitchik S (1993) rIFNα2a in combination with dacarbazine in the treatment of metastatic malignant melanoma. Analysis of long-term responding patients. Cancer Immunol Immunother 37: 61

    PubMed  Google Scholar 

  29. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer-cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316: 889

    PubMed  Google Scholar 

  30. Rosenberg SA, Lotze MT, Yang JC, Aebersold PM, Lineban WM, Seipp CA, White DE (1989) Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol 7: 1863

    PubMed  Google Scholar 

  31. Rosenstein M, Ettinghausen SF, Rosenberg SA (1986) Extravasation of recombinant interleukin-2. J Immunol 137: 1735

    PubMed  Google Scholar 

  32. Sertoli MR, Queirolo P, Bajetta E, Negretti E, Calabresi F, Bardugani L, Gianotti B, Cascinelli N (1992) DTIC with or without rIFNα2a at different dosages in the treatment of stage IV melanoma patients. Proc ASCO 11: 345

    Google Scholar 

  33. West WH, Taker KW, Yannelli JR, Marshall GD, Orr DW, Thurman GB, Oldham RK (1987) Constant infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med 316: 898

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Tel-Aviv Sourasky Medical Centre, 6 Weizmann Street, 64239, Tel-Aviv, Israel

    Han G. Ron, Yair Mordish, Avi Eisenthal, Moshe J. Inbar & Samario Chaitchik

  2. Sackler Faculty of Medicine, Tel-Aviv University, 6 Weizmann Street, 64239, Tel-Aviv, Israel

    Han G. Ron, Yair Mordish, Avi Eisenthal, Yehuda Skornick, Moshe J. Inbar & Samario Chaitchik

  3. Department of Surgery, Tel-Aviv Sourasky Medical Centre, 6 Weizmann Street, 64239, Tel-Aviv, Israel

    Yehuda Skornick

Authors
  1. Han G. Ron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yair Mordish
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Avi Eisenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yehuda Skornick
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Moshe J. Inbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Samario Chaitchik
    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

Ron, H.G., Mordish, Y., Eisenthal, A. et al. A phase II study of combined administration of dacarbazine and carboplatin with home therapy of recombinant interleukin-2 and interferon-α2a in patients with advanced malignant melanoma. Cancer Immunol Immunother 38, 379–384 (1994). https://doi.org/10.1007/BF01517207

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01517207

Key words

Search

Navigation