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.