Effects of recombinant human interleukin-3 in patients with relapsed small-cell lung cancer treated with chemotherapy: a dose-finding study.
OBJECTIVE
The aim of the study was to determine the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after combination chemotherapy and to evaluate the ability of rhIL-3 to influence hematopoietic recovery.


METHODS
Nineteen patients who had relapsed small-cell lung cancer (SCLC) received rhIL-3 after their second course of chemotherapy, which consisted of either cyclophosphamide, doxorubicin, and etoposide (CDE) every 3 weeks or vincristine, ifosfamide, mesna, and carboplatin (VIMP) every 4 weeks. Twenty-four hours after the last chemotherapy dose, rhIL-3 was administered subcutaneously (SC) once daily for 14 days on an outpatient basis. Escalating dosages (1, 2, 4, 8, and 16 micrograms/kg/d) of rhIL-3 were tested. Hematologic effects were evaluated by comparing blood cell recovery after chemotherapy cycle 1 and cycle 2 plus rhIL-3.


RESULTS
The adverse effects of rhIL-3 at dosages up to 8 micrograms/kg/d consisted mainly of low-grade fever and flulike symptoms. At 16 micrograms/kg, rhIL-3 headache became dose-limiting. Severe neutropenia (neutrophils less than 0.5 x 10(9)/L) after VIMP cycle 2 was shorter in duration than after cycle 1 (7 v 3 days; P less than .05). At rhIL-3 dose levels 8 and 16 micrograms/kg, hematologic effects in seven patients who were treated with VIMP showed a significant hastened recovery of leukocyte and neutrophil counts during cycle 2 compared with cycle 1 and increased monocyte and eosinophil counts in cycle 2 compared with cycle 1. rhIL-3 also increased reticulocyte and platelet counts at a dose level of 8 micrograms/kg. No significant stimulation of basophils and lymphocytes was observed. Apart from the hematologic effects, rhIL-3 also augmented the release of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and lowered cholesterol levels.


CONCLUSIONS
This study demonstrates that rhIL-3 can be safely administered after chemotherapy on an outpatient basis. rhIL-3 is tolerated well at doses up to 8 micrograms/kg/d and is biologically active in patients after myelosuppressive chemotherapy.
Postmus
P E
PE
Department of Pulmonology, University Hospital Groningen, The Netherlands.
Gietema
J A
JA
Damsma
O
O
Biesma
B
B
Limburg
P C
PC
Vellenga
E
E
de Vries
E G
EG
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000188:drug therapy*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D016207:Cytokines / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007377:Interleukin-3 / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence
D016207:Cytokines; D007377:Interleukin-3; D008055:Lipids; D011994:Recombinant Proteins