Investigational New Drugs

, Volume 10, Issue 3, pp 217–223 | Cite as

A phase II study of interleukin-2 and interferon-alpha in head and neck cancer

  • Stimson P. Schantz
  • Isaiah Dimery
  • Scott M. Lippman
  • Gary L. Clayman
  • Candice Pellegrino
  • Rudolfo Morice
Clinical Studies


The capacity to modulate host response against metastatic head and neck cancer may eventually lead to improved survival. This phase II study in patients with advanced head and neck cancer evaluated the efficacy of combination systemic recombinant interleukin-2 (IL-2) and interferon-alpha (INF-a) and evaluated laboratory correlates between tumor response and a) tumor differentiation and b) NK cell activation. Five of fourteen patients responded; two had partial responses and three had transient responses (one complete and two partial, each lasting less than four weeks). Patients that responded had relatively lesser tumor burden and poorly-differentiated metastases. No response was observed in those few individuals in whom natural immune function was only minimally enhanced by therapy. Major toxicity, including but not limited to fever, fatigue and pulmonary compromise, allowed only 3 of 14 patients to complete three cycles of therapy. This preliminary phase II study shows that combination IL-2/INF-a therapy has clinical anti-tumor activity and that the level of NK cell activation and the degree of tumor differentiation may correlate with response.

Key words

interleukin-2 interferon-alpha head and neck cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cameron RB, McIntosh JK, Rosenberg SA. Synergistic antitumor effects of combination immunotherapy with recombinant interleukin-2 and recombinant hybrid alphainterferon in the treatment of established murine hepatic metastases. Cancer Res 48:5810–5817, 1988PubMedGoogle Scholar
  2. 2.
    Rosenberg SA, Lotze MT, Yang JC,et al. Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol 7:1863–1874, 1989PubMedGoogle Scholar
  3. 3.
    Lee KH, Talpaz M, Rothberg JM,et al: Concomitant administration of recombinant human interleukin-2 and recombinant interferon-alpha-2A in cancer patients: a phase I study. J Clin Oncol 17:1726–1732, 1989Google Scholar
  4. 4.
    Smith KA, Interleukin-2: Inception, impact, and implications. Science 240:1169–1176, 1988PubMedGoogle Scholar
  5. 5.
    Goldstein D, Lazlo J: Interferon therapy in cancer: From imaginon to interferon. Cancer Res 46:4315–4329, 1986PubMedGoogle Scholar
  6. 6.
    Schantz SP, Clayman G, Racz T,et al.: The in-vivo biologic effect of interleukin-2 and interferon alpha on natural immunity in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 116:1302–1308, 1990PubMedGoogle Scholar
  7. 7.
    Sondel PM, Kohler PC, Hank JA,et al: Clinical and immunological effects of recombinant interleukin-2 given by repetitive weekly cycles to patients with cancer. Cancer Res 48:2561–2567, 1988PubMedGoogle Scholar
  8. 8.
    Thompson JA, Lee DL, Cox WW,et al.: Recombinant interleukin-2 toxicity, pharmacokinetics, and immunomodulatory effects in a phase I trial. Cancer Res 47:4202–4207, 1987PubMedGoogle Scholar
  9. 9.
    Phillips JH, Gemlo BT, Myers WW, Rayner AA, Lanier LL: In vivo and in vitro activation of natural killer cells in advanced cancer patients undergoing combined recombinant interleukin-2 and LAK cell therapy. J Clin Oncol 5:1933–1941, 1987PubMedGoogle Scholar
  10. 10.
    Schantz SP, Ordonez NG: Quantitation of natural killer cell function and risk of metastatic poorly differentiated head and neck cancer. Nat Immun Cell Growth Regul 10:278–288, 1991PubMedGoogle Scholar
  11. 11.
    Schantz SP, Brown BW, Lira E, Taylor DL, Beddingfield N: Evidence for the role of natural immunity in the control of metastatic spread of head and neck cancer. Cancer Immunol Immunother 25:141–148, 1987PubMedGoogle Scholar
  12. 12.
    Saranath D, Panchal RG, Nair R,et al.: Oncogene amplification in squamous cell carcinoma of the oral cavity. Jpn J Cancer Res 80:430–437, 1989PubMedGoogle Scholar
  13. 13.
    Parkinson DR, Schantz SP: The immunobiological therapy of head and neck cancer. In: Snow G, Clark JR (eds). Multimodality Therapy for Head and Neck Cancers, George Thieme Verlag, Stuttgart, pp. 147–159, 1992.Google Scholar
  14. 14.
    Nicolson G, Milas L (eds): Cancer invasion and metastasis. Biologic and therapeutic aspects. Raven Press, New York, 1984.Google Scholar
  15. 15.
    Takasugi M, Mickey MR, Terasaki PI: Reactivity of lymphocytes from normal persons on cultured tumor cells. Cancer Res 33:2898–2902, 1973PubMedGoogle Scholar
  16. 16.
    Schantz SP, Shillitoe EJ, Brown B, Campbell B: Natural killer cell activity and head and neck cancer: a clinical assessment. J Natl Cancer Inst 77:869–875, 1986PubMedGoogle Scholar
  17. 17.
    Mickel RA, Kessler DJ, Taylor JMG, Lichtenstein A: Natural killer cell cytotoxicity in the peripheral blood, cervical lymph nodes, and tumor of head and neck cancer patients. Cancer Res 48:5017–5022, 1988PubMedGoogle Scholar
  18. 18.
    Guo M, Rabin BS, Johnson JT, Paradis IL: Lymphocyte phenotypes at tumor margins in patients with head and neck cancer. Head Neck Surg 9:265–271, 1987PubMedGoogle Scholar
  19. 19.
    Kärre K, Ljunggren HG, Piontek G, Kiessling R: Selective rejection of H-2 deficient lymphoma variants suggests alternative immune defense strategy. Nature 319:675–678, 1986PubMedGoogle Scholar
  20. 20.
    Urba S, Forastiere AA, Amrein PC, Wolf GT, Zeffren J: A phase-II pilot study of concomitantly administered recombinant human interleukin-2 (rIL-2) and roferon-a (rIFN) in patients (pts) with locally recurrent or metastatic head and neck cancer (H & N CA). Proc Am Soc Clin Onc 10:208, 1991Google Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • Stimson P. Schantz
    • 1
  • Isaiah Dimery
    • 1
  • Scott M. Lippman
    • 1
  • Gary L. Clayman
    • 1
  • Candice Pellegrino
    • 1
  • Rudolfo Morice
    • 1
  1. 1.Departments of Head and Neck Surgery and Medical Oncology, Section of Head and Neck Oncology and Pulmonary MedicineUniversity of Texas M.D. Anderson Cancer CenterHoustonUSA

Personalised recommendations