A phase I and pharmacokinetic study of subcutaneously-administered recombinant human interleukin-4 (rhuIL-4) in patients with advanced cancer.
OBJECTIVE
To investigate the pharmacokinetics and tolerability of recombinant human interleukin-4 (rhuIL-4), administered by daily subcutaneous injection, in patients with advanced cancer.


METHODS
Fourteen patients with advanced cancer treated with rhuIL-4 at escalating dose levels of 0.25, 1.0 and 5.0 microg/kg/day, on days 1, 8-17, and 28-57. The primary endpoints of the study were toxicity of rhuIL-4 and the determination of the pharmacokinetics of rhuIL-4 when given by subcutaneous injection. Secondary endpoints included effects on blood counts, hematopoietic cell precursors, and various immunologic parameters.


RESULTS
rhuIL-4 was well tolerated at all three dose levels. Detectable serum levels of IL-4 were found in patients at the 1.0 and 5.0 microg/kg/day dose levels. Peak serum IL-4 levels were achieved about 2 h after injection and IL-4 was still detectable 8 h after injection. No grade 4 toxicities were observed and grade 3 toxicities were confined to fever, headache and raised hepatic alkaline phosphatase. No consistent hematological or immunologic effects were observed. Although therapeutic efficacy was not an endpoint, one complete response (Hodgkin's disease) was observed. One patient with chronic lymphocytic leukemia progressed on therapy.


CONCLUSIONS
rhuIL-4 up to 5.0 microg/kg/day is well tolerated when given by subcutaneous injection. Biologically relevant serum IL-4 levels can be achieved and sustained for at least 8 h after a single injection.
Davis
I D
ID
Ludwig Institute for Cancer Research, Melbourne, Australia. Ian.Davis@ludwig.edu.au
Maher
D W
DW
Cebon
J S
JS
Green
M D
MD
Fox
R M
RM
McKendrick
J J
JJ
Rybak
M E
ME
Boyd
A W
AW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015847:Interleukin-4 / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D015847:Interleukin-4