Phase I study of prolonged low-dose subcutaneous recombinant interleukin-2 (IL-2) in patients with advanced cancer.
The present trial was designed to assess the feasibility of subcutaneous low-dose interleukin-2 (IL-2) given for 3 months in an outpatient setting. Twenty patients with advanced cancers (16 metastatic renal cell carcinoma) were included in this phase I study at the following three dose levels: 1, 3, and 6 x 10(6) IU/day (groups of 6, 6, and 8 patients, respectively). IL-2 was administered once daily 6 days a week for 12 weeks. Complete therapy was achieved in 13 of 20 patients, whereas 5 of 20 received at least 5 weeks of IL-2. Minor dose-dependent toxicities were observed including fatigue, transient grade 2-3 fever (11 of 18), and grade 1-2 digestive disorders (6 of 18) without significant biologic modifications but two cases of hypothyroidism. Doses were decreased from 6 to 3 x 10(6) IU/day in one patient (fever and allergic edema). All patients developed transient subcutaneous nodules at the injection sites. These side effects never required hospitalization nor discontinuation of therapy. A dose-dependent and sustained increase in peripheral blood eosinophils and lymphocytes was observed, demonstrating that subcutaneous injections in this low-dose range could have similar biologic effects to those achieved with more intensive schedules. Because it is safe, practicable, and low in cost, we conclude that s.c. low-dose IL-2 could be useful for the design of immunomodulation trials with potential new application fields.
Angevin
E
E
Unité d'Immunothérapie, Institut Gustave Roussy, Villejuif, France.
Valteau-Couanet
D
D
Farace
F
F
Dietrich
P Y
PY
Lecesne
A
A
Triebel
F
F
Escudier
B
B
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy; D004361:Drug Tolerance; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000628:therapy; D008218:Lymphocytosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012449:Safety; D013997:Time Factors
D007376:Interleukin-2; D011994:Recombinant Proteins