title: Multi-cytokine therapy for advanced renal cell carcinoma: determination of the minimal effective dose.
abstract: A low-dose cytokine combination therapy was given continuously for as extended period to seven patients with advanced renal cell carcinoma to investigate adverse reactions and anti-cancer effectiveness. These cases were: five patients with metastasis; one whose surgical removal of metastatic foci resulted in a non-curative operation; and one patient administered our regimen as postoperative treatment for locally-advanced cancer. Our regimen was started with a subcutaneous injection of a two-drug combination: 6x10(6) units interferon-alfa (IFN-alpha) and 1x10(6) units interferon-gamma (IFN-gamma) to per week iwall our patients; subcutaneous injection of 1.4x10(6) units interleukin-2 (IL-2) per week was added for three patients who showed insufficient therapeutic effects. The combination therapy was performed for 31 months maximum. Objective adverse reactions were very slight in all patients, thus they could be treated as outpatients. Therapeutic outcomes of IFN-alpha and IFN-gamma combination therapy were assessed as CR in one, PR in one, NC in 2 and PID in one patient. One patient showed NC for 27 months. Three patients, one PR case, one NC case and one PD case, were shifted to the three-drug combination therapy and the results after shifting were assessed as 2 PR cases and one PD case. These 2 PR cases are still under treatment with a good quality of life after 31 and 24 months, respectively. These results suggest the possibility of prolonging survival-time by combining continuous low-dose cytokine with conventional local treatments.
authors.affiliation: Department of Urology, Saitama Medical School, Iruma-Gun, Japan.
authors.forename: Ikuto
authors.initials: I
authors.lastname: Hamada
authors.forename: Mikio
authors.initials: M
authors.lastname: Kato
authors.forename: Koichi
authors.initials: K
authors.lastname: Okada
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D016207:Cytokines / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007371:Interferon-gamma / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2; D007371:Interferon-gamma