Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies.
Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown to induce thyroid dysfunction in some cancer patients. The purpose of the present study was to evaluate the incidence and risk factors of this adverse autoimmune response. Triiodothyronine, thyroxine and thyrotropin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopathy (69 patients); rIL-2 was administered intravenously in 5-day cycles (18 x 10(6)-24 x 10(6) IU.m-2.day-1) either alone in 79 cases or in combination with autologous bone marrow transplantation in 26 cases, with interferon-gamma in 37 cases, with tumor necrosis factor-alpha in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was present upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9%) patients exhibited peripheral hypothyroidism, out of which four exhibited biphasic thyroiditis. Another five (3.4%) patients developed transient hyperthyroidism. Anomaly could not be classified in three patients. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abnormalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoimmune antibodies. Antithyroid antibodies were detected in 60.9% of patients with this complication. Thyroid-stimulating antibodies were never detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Vialettes
B
B
Department of Internal Medicine and Nutrition, Hospital la Timone, Marseille, France.
Guillerand
M A
MA
Viens
P
P
Stoppa
A M
AM
Baume
D
D
Sauvan
R
R
Pasquier
J
J
San Marco
M
M
Olive
D
D
Maraninchi
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects*; D015994:Incidence; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010641:Phenotype; D011994:Recombinant Proteins; D012307:Risk Factors; D013959:Thyroid Diseases / Q000209:etiology*
D001323:Autoantibodies; D007376:Interleukin-2; D011994:Recombinant Proteins