This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tamura, T. Articles by Saijo, N. Search for Related Content PubMed PubMed Citation Articles by Tamura, T. Articles by Saijo, N.

Phase I Study of Combination Therapy with Interleukin 2 and ß-Interferon in Patients with Advanced Malignancy¹

Department of Internal Medicine, National Cancer Center Hospital [T. T., Y. S., T. S., K. E., M. S., Y. F., N. S.], Pharmacology Division, National Cancer Center Research Institute [K. N., K. M., M. B.], 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan

Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and ß-interferon (IFN-ß) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-ß was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-ß by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Doselimiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-ß were 1.1 x 10⁶ U/m²/day for rIL-2 and 6.0 x 10⁶ IU/m²/day for IFN-ß. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.

¹ This study was supported in part by Grants-in-Aid for Cancer Research, and for Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare.

Received 6/21/88. Revised 10/28/88. Accepted 11/ 1/88.

This article has been cited by other articles:

				T. Y. Shibuya, S. Kim, K. Nguyen, J. Do, C. E. McLaren, K.-T. Li, W.-P. Chen, P. Parikh, A. Wadhwa, X. Zi, et al. Bioactive Suture: A Novel Immunotherapy for Head and Neck Cancer Clin. Cancer Res., October 15, 2004; 10(20): 7088 - 7099. [Abstract] [Full Text] [PDF]