Granulocyte-macrophage colony-stimulating factor and interferon-alpha 2B in patients with advanced renal cell carcinoma.
OBJECTIVE
Biological response modifiers such as interferon-alpha2B (IFN-alpha2B) have well-known clinical activities against renal cell carcinoma (RCC). Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has antitumorigenic effects both in vitro and in vivo. Therefore, a phase-I/II trial of IFN-alpha2B and GM-CSF was performed in patients with metastatic RCC.


METHODS
21 patients in groups of 3 patients received GM-CSF at 7 different dose levels (15-300 microg) subcutaneously in combination with IFN-alpha2B at a fixed dose of 10 x 10(6) IU s.c. three times weekly for 12 weeks.


RESULTS
Two complete remissions have been observed, both with lung metastases only. With increasing dose levels of GM-CSF a slight tendency to more toxicity was detectable. Due to grade-3 toxicities 5 patients (24%) dropped out of the treatment schedule. Increases in WBC, neutrophils, lymphocytes, and monocytes were noted but were not related to the dose levels of GM-CSF.


CONCLUSIONS
Results demonstrate that simultaneous administration of GM-CSF and IFN-alpha2B is tolerated up to doses of 120-150 microg GM-CSF three times weekly. But there is no additional antitumorigenic effect of GM-CSF because the overall response rate of the combined administration of GM-CSF/IFN-alpha2B is similar to IFN-alpha2B alone and there is no obvious dose relationship between increasing doses of GM-CSF and the responses.
Lümmen
G
G
Department of Urology, University of Essen Medical School, Essen, Germany.
Sperling
H
H
Luboldt
H
H
Otto
T
T
Rübben
H
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor