A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides - 09/08/11
, Matthew L. Sherman, MD b, Gary S. Wood, MD c, Timothy M. Kuzel, MD d, Elise Olsen, MD e, Francine Foss, MD f, Robert J. Laliberté, MS b, John L. Ryan, MD, PhD b, Kristilyn Zonno, BS b, Alain H. Rook, MD g
Reprint requests: Madeleine Duvic, MD, Department of Dermatology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 434, Houston, TX, 77030.Houston, Texas; Cambridge, Massachusetts; Madison, Wisconsin; Chicago, Illinois; Durham, North Carolina; New Haven, Connecticut; and Philadelphia, Pennsylvania
Abstract |
Background |
Interleukin-12 (IL-12) increases Th1 cytokines, natural killer (NK) cells, and cytotoxic T-cell activities. Progression of mycosis fungoides is associated with Th2 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.
Le texte complet de cet article est disponible en PDF.Abbreviations used : AE, ALT, AST, CR, CTCL, IFN-γ, MF, NCI, NK, PD, PR, rhIL-12, SC, SWAT, Th
Plan
| Presented in part at the 61st Annual Meeting of the Society for Investigative Dermatology, Chicago, IL, May 10-14, 2000, and at the 36th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, May 20-23, 2000. Supported by Wyeth Research/Genetics Institute, Cambridge, MA. We thank Scott Saunders, MD, for professional medical writing services in preparation of the manuscript. We also thank Luke Yoon, Rhea Philips, and Joan Breuer-McHam of the University of Texas M.D. Anderson Cancer Center for their analytic/laboratory support in performing immunohistochemical assays, and the National Institutes of Health K24 program for partial support of Dr Duvic’s and Rook’s salary. This research was supported in part by a General Clinical Research Center grant from NIH/NCRR (M01RR00040) awarded to the University of Pennsylvania School of Medicine. Conflicts of interest: Drs Duvic, Rook, Foss, Wood, Kuzel, and Olsen were principal investigators at their respective centers and therefore received support for the conduct of the clinical trials. Dr Sherman, Mr Laliberté, Dr Ryan, and Ms Zonno were employees of Genetics Institutes or Wyeth. |
Vol 55 - N° 5
P. 807-813 - novembre 2006 Retour au numéro
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