Background: Due to lack of success with standard chemotherapy and only modest success with immunotherapy, metastatic renal cell carcinoma (RCC) is associated with a poor prognosis. Granulocyte-macrophage-colony stimulating factor (GM-CSF) is a cytokine with potential antitumor activity, including stimulation of tumor necrosis factor (TNF) and interleukin-1 secretion. It is also a potent growth factor for and activator of antigen-presenting dendritic cells. GM-CSF toxicity may be mediated by TNF, and inhibition of TNF release by pentoxifylline (PTX) may ameliorate these toxic effects. The authors conducted a Phase II trial to determine the activity of GM-CSF in metastatic RCC and to study the effect of PTX on GM-CSF toxicity.
Methods: Twenty-four eligible patients with metastatic RCC received 10 microg/kg of GM-CSF per day, administered subcutaneously, on a 14-days-on/14-days-off schedule. Twelve patients received concurrent PTX at a dose of 400 mg administered orally 4 times per day.
Results: One patient experienced prolonged stability of disease after having progressive disease on entry. Two other patients experienced substantial slowing of their progressive disease while on study. One of these patients had rapidly progressing metastases on other immunotherapy before receiving GM-CSF. Toxicity was not diminished in patients treated with PTX; it included hyperleukocytosis, nausea, vomiting, pain, fever, skin reactions, myalgia, and fatigue.
Conclusions: GM-CSF at the dose and schedule described in this report has minor activity against metastatic RCC, and PTX does not ameliorate its side effects.