Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for metastatic renal cell cancer.
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.
Atzpodien
J
J
Department of Hematology and Oncology, Medizinische Hochschule Hannover, Germany.
Kirchner
H
H
Hänninen
E L
EL
Deckert
M
M
Fenner
M
M
Poliwoda
H
H
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
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D005472:Fluorouracil