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 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.


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 microg/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 microg/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.
Tate
J
J
Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, Ohio, USA.
Olencki
T
T
Finke
J
J
Kottke-Marchant
K
K
Rybicki
L A
LA
Bukowski
R M
RM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015539:Platelet Activation; D013922:Thrombocytosis / Q000139:chemically induced; D016896:Treatment Outcome
D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor