Phase I trial of simultaneously administered GM-CSF and IL-6 in patients with renal-cell carcinoma: Clinical and laboratory effects

Background: Metastatic renal-cell carcinoma is a neoplasm that is minimally responsive to cytotoxic chemotherapy. Tumor regression following therapy w ith cytokines such as interferon alpha and/or interleukin-2 is seen in sele cted subsets of patients. Investigations with other immunomodulatory cytoki nes, such as GM-CSF and IL-6 are therefore of interest. Patients and methods: A phase I trial of concomitantly administered granulo cyte macrophage-colony stimulating factor (3.0 mcg/kg/day s.c. d1-14) and e scalating doses of interleukin-6 (1.0, 5.0 or 10.0 mug/kg/day d1-14) was co nducted in patients with metastatic renal-cell carcinoma to explore the tox icity of the combination and its hematologic effects. Results: The most common side effects seen were fever, fatigue and arthralg ias. Dose limiting toxicity included thrombocytosis and hyperbilirubinemia in patients receiving 10 mug/kg/day of IL-6. The hematologic effects of IL- 6 and GM-CSF included leukocytoses and thrombocytosis, with increases in pe ripheral blood progenitors (BFU-E, CFU-GM, and CFU-GEMM). Evidence of plate let activation demonstrated by increased platelet expression of CD62 was fo und. No clinical responses were observed. Conclusions: The combination of IL-6 and GM-CSF has pleotropic hematologic effects. Further studies with this combination for the treatment of renal-c ell carcinoma are not recommended.