title: Cytokine combinations: therapeutic use in patients with advanced renal cell carcinoma.
abstract: Treatment of metastatic renal cell carcinoma (RCC) remains unsatisfactory. To enhance the antitumor effects of various cytokines, combinations of these agents have been investigated. Interleukin-2 (IL-2) and interferon-alfa (IFN-alpha) have been combined based on data from preclinical studies suggesting synergism. A review of available phase I and II trials in more than 1,400 patients indicates that response rates are approximately 20%. Complete regressions are seen in 3% to 5% of patients. To demonstrate that this combination increases overall response rates, randomized trials were required. The results of a phase III study demonstrate a significantly improved response rate (18.6%) and 1-year event-free survival (20.9%) for patients treated with continuous infusion recombinant (r) IL-2 and subcutaneous IFN-alpha compared with either cytokine alone. The toxicity of rlL-2 and IFN-alpha is related to cytokine dose and schedule, but appears less than that reported with high-dose rIL-2. Analysis of prognostic factors and surrogate marker changes have been conducted. Performance status and number of disease sites predict response. rIL-2 and IFNalpha were then combined with fluorouracil, with initial reports suggesting response rates greater than 40%. Recent reports indicate 1% to 39% of patients responding. In a group of 836 patients with metastatic RCC receiving this therapy, 25.3% responded. Randomized trials comparing chemoimmunotherapy to rIL-2 and/or IFN-alpha are now required. The biologic basis and rationale for utilization of cytokines are strong. Clinical results are consistent with improved response rates in patients receiving rIL-2 and IFN-alpha. Continued investigation of novel and new treatment approaches remains a priority.
authors.affiliation: Experimental Therapeutics Program, Cleveland Clinic Taussig Cancer Center, OH 44195, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000628:therapy*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016131:Lymphocyte Subsets / Q000187:drug effects; D009362:Neoplasm Metastasis; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D005472:Fluorouracil