PHASE-I TRIAL OF THIOTEPA, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND PREDNISONE OR PENTOXIFYLLINE IN PATIENTS WITH REFRACTORY SOLID TUMORS

In a phase I trial, 13 patients with refractory solid tumors received thiotepa, granulocyte-macrophage colony-stimulating factor (GM-CSF), a nd either prednisone or pentoxifylline (PTX) on alternate cycles. The prednisone and PTX were administered in an attempt to ameliorate toxic ity 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 an d four grade 2 or greater leukopenia. One of these patients died secon dary to E. coli sepsis. Seven patients received a thiotepa dose of 50 mg/m(2), with one experiencing grade 3 thrombocytopenia and another gr ade 3 leukopenia. The latter patient died secondary to presumed sepsis . The five remaining patients at the 50 mg/m(2) dose did not experienc e greater than grade 1 hematologic toxicity. Serum tumor necrosis fact or levels were not increased by GM-CSF. Patients in this trial were no t evaluable for amelioration of GM-CSF toxicity as too few received a second cycle of treatment. We conclude that thiotepa doses greater tha n 50 mg/m(2) are not tolerated due to severe thrombocytopenia which is not diminished by the administration of GM-CSF.