In a phase I trial, 13 patients with refractory solid tumors received thiotepa, granulocyte-macrophage colony-stimulating factor (GM-CSF), and either prednisone or pentoxifylline (PTX) on alternate cycles. The prednisone and PTX were administered in an attempt to ameliorate toxicity related to GM-CSF. Of the first six patients treated at a thiotepa dose of 60 mg/m(2), five experienced grade 3 or 4 thrombocytopenia and four grade 2 or greater leukopenia. One of these patients died secondary to E. coli sepsis. Seven patients received a thiotepa dose of 50 mg/m(2), with one experiencing grade 3 thrombocytopenia and another grade 3 leukopenia. The latter patient died secondary to presumed sepsis. The five remaining patients at the 50 mg/m(2) dose did not experience greater than grade 1 hematologic toxicity. Serum tumor necrosis factor levels were not increased by GM-CSF. Patients in this trial were not evaluable for amelioration of GM-CSF toxicity as too few received a second cycle of treatment. We conclude that thiotepa doses greater than 50 mg/m(2) are not tolerated due to severe thrombocytopenia which is not diminished by the administration of GM-CSF.

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