A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides

Interleukin-12 (IL-12) increases Th 1 cytokines, natural killer (NK) cells, and cytotoxic T-cell activities. Progression of mycosis fungoides is associated with Th 2 cytokines produced by a clonal proliferation of epidermotropic T-helper cells. To determine the safety and efficacy of subcutaneous re...

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Bibliographic Details
Published in:Journal of the American Academy of Dermatology 2006-11, Vol.55 (5), p.807-813
Main Authors: Duvic, Madeleine, Sherman, Matthew L., Wood, Gary S., Kuzel, Timothy M., Olsen, Elise, Foss, Francine, Laliberté, Robert J., Ryan, John L., Zonno, Kristilyn, Rook, Alain H.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - administration & dosage
Adjuvants, Immunologic - adverse effects
Adjuvants, Immunologic - therapeutic use
Biological and medical sciences
Dermatology
Disease Progression
Drug Administration Schedule
Female
Hematologic and hematopoietic diseases
Humans
Injections, Subcutaneous
Interleukin-12 - administration & dosage
Interleukin-12 - adverse effects
Interleukin-12 - therapeutic use
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Mycosis Fungoides - drug therapy
Mycosis Fungoides - pathology
Neoplasm Staging
Recombinant Proteins - administration & dosage
Recombinant Proteins - adverse effects
Recombinant Proteins - therapeutic use
Skin Neoplasms - drug therapy
Skin Neoplasms - pathology
Treatment Outcome
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Summary:Interleukin-12 (IL-12) increases Th 1 cytokines, natural killer (NK) cells, and cytotoxic T-cell activities. Progression of mycosis fungoides is associated with Th 2 cytokines produced by a clonal proliferation of epidermotropic T-helper cells. To determine the safety and efficacy of subcutaneous recombinant human IL-12 (rhIL-12) in early mycosis fungoides (MF; stage IA-IIA) in a multi-center, open label clinical trial. rhIL-12 was administered biweekly (100 ng/kg for 2 weeks; 300 ng/kg thereafter). A modified severity-weighted assessment tool (SWAT) and the longest diameter of 5 index lesions measured efficacy. Twenty-three MF patients (stage IA, 12 patients; IB, 9; and IIA, 2) had previously received >3 therapies. Ten of 23 patients (43%) achieved partial responses (PR); 7 (30%) achieved minor responses; and 5 (22%) had stable disease. The duration of PRs ranged from 3 to more than 45 weeks. Twelve (52%) ultimately progressed with mean time to progressive disease of 57 days (range, 28-805). Ten completed 6 months of therapy; 1 completed 24 months. Of patients not completing 6 months of therapy, 6 progressed and 6 others discontinued because of adverse events or withdrew consent. Seventeen patients had treatment-related adverse events that were generally mild or moderate in severity, including asthenia, headache, chills, fever, injection site reaction, pain, myalgia, arthralgia, elevated aspartate and alanine aminotransferase levels, anorexia, and sweating. One patient in PR died of hemolytic anemia, possibly exacerbated by rhIL-12 treatment. The original company was purchased during the conduct of the trial and rhIL-12 is currently unavailable. The quality of life data were not available for inclusion. Twice-weekly subcutaneously administered rhIL-12 (100 ng/kg escalated to 300 ng/kg) showed antitumor activity with a response rate of 43% in refractory patients. It was relatively well-tolerated in early-stage MF.
ISSN:0190-9622
1097-6787
DOI:10.1016/j.jaad.2006.06.038