THE TOLERABILITY OF CONTINUOUS INTRAVENOUS-INFUSION OF INTERLEUKIN-3 AFTER DHAP CHEMOTHERAPY IN PATIENTS WITH RELAPSED MALIGNANT-LYMPHOMA -A PHASE-I STUDY

The objective of this phase-I study was to establish the maximum toler able dose of recombinant human interleukin-3 (rhIL-3) after salvage ch emotherapy in patients with malignant lymphoma. Twenty-one patients wi th relapsed Hodgkin's disease or intermediate/high-grade non-Hodgkin's lymphoma received rhIL-3 after the second cycle of DHAP chemotherapy (cisplatin, cytosine-arabinoside, dexamethasone). Cycles 1 and 3 were given without rhIL-3. The rhIL-3 was administered as a continuous intr avenous infusion for 10 days starting 48 h after chemotherapy in cycle 2. Five different dose levels of rhIL-3 (0.25, 1.0, 2.5, 5.0, and 10. 0 mug/kg/day) were sequentially tested. At the three lowest dose level s one double-blinded placebo was included for every four patients per dose level. Low-grade fever occurred in 15/21 patients, unrelated to t he dose of rhIL-3. Nausea and vomiting (grade 1-2) occurred in seven p atients. Headache was dose related, with 3/4 patients at a dose of 10 mug/kg/day experiencing troublesome grade-2 headache precluding furthe r dose escalation. Facial flushing developed in 3/8 patients at the hi ghest dose levels of rhIL-3. There was a significant increase in eosin ophil count during rhIL-3 (p = 0.03 cycle 2 vs cycle 1 and p = 0.002 c ycle 2 vs cycle 3) without accompanying clinical signs or symptoms. No increase in basophil count was observed. There were no increased plas ma levels of interleukin-6 or macrophage colony-stimulating factor (M- CSF) during rhIL-3. We conclude that rhIL-3 can be safely administered as a continuous intravenous infusion for 10 days after DHAP chemother apy. Dose-limiting side effects, especially headache, occur at a dose of 10 mug/kg/day.