A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer.
We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis.
Crown
J
J
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Jakubowski
A
A
Kemeny
N
N
Gordon
M
M
Gasparetto
C
C
Wong
G
G
Sheridan
C
C
Toner
G
G
Meisenberg
B
B
Botet
J
J
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy*; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007022:Hypotension / Q000139:chemically induced; D007375:Interleukin-1 / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000097:blood / Q000188:drug therapy*; D009503:Neutropenia / Q000517:prevention & control; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000097:blood / Q000188:drug therapy*
D001786:Blood Glucose; D007375:Interleukin-1; D011994:Recombinant Proteins; D005472:Fluorouracil; D006854:Hydrocortisone