title: Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for metastatic renal cell cancer.
abstract: Recent clinical trials for the biological therapy of solid tumours have used recombinant human cytokines in combination with conventional chemotherapy. In patients with progressive metastatic renal cell carcinoma, we established a three-drug combination comprising interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU), using a regimen which allows outpatient therapy. Treatment consisted of 8 weeks each of IFN-alpha [6-9 MU/m2 once to three times weekly subcutaneously (sc)] combined sequentially with IL-2 (5-20 MU/m2 thrice weekly sc for 4 weeks) and 5-FU [750 mg/m2 intravenously (i.v.) weekly for 4 weeks]. Among the first 35 patients treated, there were 4 complete (11.4%) and 13 partial responders (37.1%), with an overall objective response rate of 48.6% (95% confidence interval 32-66%). Regressions occurred in local relapse, in lung, lymph node, bone, pleural, renal and thyroid metastases. Median response duration was calculated at 7+ months. An additional 13 patients (37.1%) were stable throughout therapy and thereafter (median of 6+ months). Response rate of this three-drug combination regimen compared favourably with single agent IFN-alpha (objective response rate approximately 16%) and against the sc IFN-alpha/IL-2 combination (objective response rate approximately 28%). Systemic toxicity was mild to moderate with no severe 5-FU-related mucositis and no dose-limiting adverse effects of sc IL-2. While the exact mechanisms of the potentially additive or synergistic effects of 5-FU and IFN-alpha/IL-2 remain to be established in more detail, it appears that the sequential use of IFN-alpha/IL-2 and IFN-alpha/5-FU in metastatic renal carcinoma further enhances the therapeutic index of IFN-alpha/IL-2-based biological therapy. Based on the present data, combined biochemotherapy may be a promising new approach to the therapy of advanced renal cancer.
authors.affiliation: Department of Hematology and Oncology, Medizinische Hochschule Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Atzpodien
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: E L
authors.initials: EL
authors.lastname: Hänninen
authors.forename: M
authors.initials: M
authors.lastname: Deckert
authors.forename: M
authors.initials: M
authors.lastname: Fenner
authors.forename: H
authors.initials: H
authors.lastname: Poliwoda
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D005472:Fluorouracil