Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study.
Recombinant interleukin-2 (rIL-2; EuroCetus, Amsterdam, Netherlands) was studied in an outpatient phase II trial in 14 patients with progressive metastatic renal carcinoma, malignant melanoma, and colorectal cancer. Escalating doses of rIL-2 were administered as subcutaneous bolus every 12 hours, starting at 0.3 million U/m2/d. A 100% dose increase occurred at weekly intervals, up to a maximum of 2.4 million U/m2/d. Responding patients or patients with stable disease after 4 weeks of rIL-2 (n = 9) were continued on maintenance therapy at 1.8 million U/m2 of rIL-2 administered once weekly. After 12 weeks of therapy, one renal cell cancer patient had a partial regression in lung metastases. Bolus injection of rIL-2 (1.2 million U/m2) resulted in peak serum levels of 25 to 30 U/ml. Toxicity of this regimen was moderate, with local inflammation at the injection sites, grade I-II (World Health Organization) malaise, nausea and/or vomiting, and fevers in 70% to 100% of patients treated. Thyroid dysfunction was observed in 10 patients receiving subcutaneous rIL-2; four of these patients had laboratory evidence of hyperthyroidism, and one had hypothyroidism. rIL-2-induced toxicity reversed spontaneously after cessation of treatment. In all patients receiving rIL-2, a dose-dependent increase in peripheral blood lymphocyte and eosinophil counts was noted, with a mean of 2.6 and 3.8 x 1,000/microliters after 4 weeks of therapy; mean lymphocyte and eosinophil counts were measured at 2.0 and 2.4 x 1,000/microliters in patients who received prior high-dose chemotherapy, compared with 3.2 and 5.1 x 1,000/microliters in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)
Atzpodien
J
J
Department of Hematology, Medizinische Hochschule MHH, University Medical Center, Hannover, FRG.
Körfer
A
A
Evers
P
P
Franks
C R
CR
Knüver-Hopf
J
J
Lopez-Hänninen
E
E
Fischer
M
M
Mohr
H
H
Dallmann
I
I
Hadam
M
M
D000855:Anorexia / Q000139:chemically induced; D000906:Antibodies / Q000032:analysis; D004341:Drug Evaluation; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced; D007111:Immunity, Cellular / Q000187:drug effects; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007964:Leukocytosis / Q000139:chemically induced; D008214:Lymphocytes / Q000187:drug effects; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use
D000906:Antibodies; D007376:Interleukin-2; D011994:Recombinant Proteins