Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy.
Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) 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-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta 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. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. 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.
Tamura
T
T
Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
Sasaki
Y
Y
Shinkai
T
T
Eguchi
K
K
Sakurai
M
M
Fujiwara
Y
Y
Nakagawa
K
K
Minato
K
K
Bungo
M
M
Saijo
N
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007370:Interferon Type I / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008214:Lymphocytes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010641:Phenotype; D011994:Recombinant Proteins / Q000008:administration & dosage
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins