Sequential administration of interferon-gamma, GM-CSF, and interleukin-2 in patients with metastatic renal cell carcinoma: results of a phase II trial.
Various cytokine combinations have been tested for efficacy in the treatment of metastatic renal cell carcinoma (MRCC). Because several immunologic synergisms between granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been demonstrated, this phase II trial was conducted on the efficacy and toxicity of subcutaneous, sequentially administered, interferon-gamma (IFNgamma), GM-CSF, and IL-2. Fifty-five consecutive patients with MRCC were treated with 100 microg recombinant IFNgamma1b administered thrice weekly during weeks 1 and 4, followed by 400 microg GM-CSF on 5 consecutive days during weeks 2 and 5. In weeks 3 and 6, patients received 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was repeated every 8 weeks. Five (10%) of patients experienced an objective response (complete response [CR]: 2%, partial response [PR]: 8%). Fourteen (26%) patients had stable disease with a median duration of 19 months (6-47+). The median overall survival was 12 months (range: 0.3-44 months). No toxicity greater than World Health Organization grade II was observed, with fever (43%) and erythema (43%) being the most frequent side effects. Compared with other phase II trials with IFN-gamma and IL-2 alone, the addition of GM-CSF failed to improve response or survival in patients with MRCC.
Schmidinger
M
M
Department of Medicine I, University Hospital, Vienna, Austria.
Steger
G
G
Wenzel
C
C
Locker
G J
GJ
Budinsky
A C
AC
Brodowicz
T
T
Kramer
G
G
Marberger
M
M
Zielinski
C C
CC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004359:Drug Therapy, Combination; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D015996:Survival Rate
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor