Repetitive weekly cycles of 4-day continuous infusion of recombinant interleukin-2: a phase I study.
A phase I trial was performed with a new interleukin-2 (IL-2) given as a continuous intravenous infusion in patients with solid tumors. The objectives of the study were to examine the feasibility of administering IL-2 in 4-day cycles for 4 consecutive weeks, and to investigate the response pattern of peripheral blood lymphocytes. Tumor necrosis factor (TNF) and IL-2 serum concentrations were also measured. Prior to this study, IL-2 had been tested at increasing dosages during one 4-day cycle, and it appeared that a dose of 1300 mcg/m2/day was tolerated. However, when this treatment schedule was maintained for 4 consecutive weeks, the maximum tolerated dose was 430 mcg/m2/day. In this schedule, a dose-dependent progressive increase in rebound lymphocyte count occurred after each weekly cycle, resulting in a 5-70-fold increase after the 4th cycle. Serum TNF peak concentrations also showed a tendency to increase during each subsequent cycle, while serum IL-2 peak concentrations showed a paradoxical decrease. Clinical toxicity comprised several events, which, possibly, could be ascribed to autoimmune phenomena. Myocardial infarction as a late toxicity of IL-2 is suggested. One complete response (renal carcinoma) and two partial responses (renal and breast carcinoma) were documented, one of these occurring in a patient who previously had shown a transient response on interferon therapy.
Punt
K C
KC
Department of Medical Oncology, Rotterdam Cancer Institute, The Netherlands.
Jansen
R L
RL
De Mulder
P H
PH
Batchelor
D
D
Galazka
A
A
Bolhuis
R L
RL
Stoter
G
G
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000139:chemically induced; D004334:Drug Administration Schedule; D004679:Encephalomyelitis / Q000139:chemically induced; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007037:Hypothyroidism / Q000139:chemically induced; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012466:Salivary Gland Diseases / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007155:Immunologic Factors; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha