title: The tolerability of continuous intravenous infusion of interleukin-3 after DHAP chemotherapy in patients with relapsed malignant lymphoma. A phase-I study.
abstract: The objective of this phase-I study was to establish the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after salvage chemotherapy in patients with malignant lymphoma. Twenty-one patients with 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 intravenous 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 micrograms/kg/day) were sequentially tested. At the three lowest dose levels one double-blinded placebo was included for every four patients per dose level. Low-grade fever occurred in 15/21 patients, unrelated to the dose of rhIL-3. Nausea and vomiting (grade 1-2) occurred in seven patients. Headache was dose related, with 3/4 patients at a dose of 10 micrograms/kg/day experiencing troublesome grade-2 headache precluding further dose escalation. Facial flushing developed in 3/8 patients at the highest dose levels of rhIL-3. There was a significant increase in eosinophil count during rhIL-3 (p = 0.03 cycle 2 vs cycle 1 and p = 0.002 cycle 2 vs cycle 3) without accompanying clinical signs of symptoms. No increase in basophil count was observed. There were no increased plasma 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 chemotherapy. Dose-limiting side effects, especially headache, occur at a dose of 10 micrograms/kg/day.
authors.affiliation: Department of Hematology, University Hospital St. Radboud Nijmegen.
authors.forename: J M
authors.initials: JM
authors.lastname: Raemaekers
authors.forename: G W
authors.initials: GW
authors.lastname: van Imhoff
authors.forename: L F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: J A
authors.initials: JA
authors.lastname: Hessels
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000002:abnormalities; D002945:Cisplatin / Q000008:administration & dosage; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004361:Drug Tolerance; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007262:Infusions, Intravenous; D007377:Interleukin-3 / Q000008:administration & dosage* / Q000633:toxicity; D015850:Interleukin-6 / Q000097:blood; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D003561:Cytarabine; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor; D002945:Cisplatin