Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression.
Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.
Tepler
I
I
Beth Israel Hospital, Boston, MA 02215.
Elias
A
A
Kalish
L
L
Shulman
L
L
Strauss
G
G
Skarin
A
A
Lynch
T
T
Levitt
D
D
Resta
D
D
Demetri
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*
D007377:Interleukin-3; D011994:Recombinant Proteins