TY - JOUR
T1 - A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides
AU - Duvic, Madeleine
AU - Sherman, Matthew L.
AU - Wood, Gary S.
AU - Kuzel, Timothy M.
AU - Olsen, Elise
AU - Foss, Francine
AU - Laliberté, Robert J.
AU - Ryan, John L.
AU - Zonno, Kristilyn
AU - Rook, Alain H.
PY - 2006/11
Y1 - 2006/11
N2 - Background: 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. Objective: 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. Methods: 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. Results: 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. Limitations: 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. Conclusion: 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.
AB - Background: 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. Objective: 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. Methods: 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. Results: 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. Limitations: 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. Conclusion: 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.
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U2 - 10.1016/j.jaad.2006.06.038
DO - 10.1016/j.jaad.2006.06.038
M3 - Article
C2 - 17052486
AN - SCOPUS:33749684290
SN - 0190-9622
VL - 55
SP - 807
EP - 813
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 5
ER -