Background:Metastatic renal-cell carcinoma is a neoplasm that is minimally responsive to cytotoxic chemotherapy. Tumor regression following therapy with cytokines such as interferon alpha and/or interleukin-2 is seen in selected subsets of patients. Investigations with other immunomodulatory cytokines, such as GM-CSF and IL-6 are therefore of interest.
Patients and methods:A phase I trial of concomitantly administered granulocyte macrophage-colony stimulating factor (3.0 mcg/kg/day s.c. d1–14) and escalating doses of interleukin-6 (1.0, 5.0 or 10.0 µg/kg/day d1–14) was conducted in patients with metastatic renal-cell carcinoma to explore the toxicity of the combination and its hematologic effects.
Results:The most common side effects seen were fever, fatigue and arthralgias. Dose limiting toxicity included thrombocytosis and hyperbilirubinemia in patients receiving 10 µg/kg/day of IL-6. The hematologic effects of IL-6 and GM-CSF included leukocytoses and thrombocytosis, with increases in peripheral blood progenitors (BFU-E, CFU-GM, and CFU-GEMM). Evidence of platelet activation demonstrated by increased platelet expression of CD62 was found. 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-cell carcinoma are not recommended.