TY - JOUR
T1 - Antitumor activity of DAB389IL-2 fusion toxin in mycosis fungoides
AU - Saleh, M. N.
AU - LeMaistre, C. F.
AU - Kuzel, T. M.
AU - Foss, F.
AU - Platanias, L. C.
AU - Schwartz, G.
AU - Ratain, M.
AU - Rook, A.
AU - Freytes, C. O.
AU - Craig, F.
AU - Reuben, J.
AU - Sams, M. W.
AU - Nichols, J. C.
PY - 1998
Y1 - 1998
N2 - Background: DAB389IL-2 is a novel fusion toxin that retargets the cytotoxic A-chain of diphtheria toxin to interleukin-2 (IL-2) receptor- expressing tumors. Objective: The purpose of this phase I trial was to study the toxicity, maximum tolerated dose, and clinical efficacy of DAB389IL-2 in IL-2 receptor expressing lymphoproliferative malignancies, including cutaneous T-cell lymphoma. Methods: DAB389IL-2 was administered intravenously daily for 5 days every 3 weeks. Dose escalation occurred between patient groups. Patients were monitored for laboratory and clinical toxicity, kinetics, immune response, and clinical efficacy. Results: Thirty- five patients with cutaneous T-cell lymphoma (including 30 patients with mycosis fungoides) were treated. Previously, conventional therapy had not worked for 34 of the patients. Thirteen patients (37%) achieved an objective response, including a complete response in five patients (14%). Complete response was achieved in patients with extensive erythroderma and tumor stage mycosis fungoides. Adverse events consisted of reversible fever/chills, hypotension, nausea/vomiting, and elevation of hepatic transaminase. Doses of less than 31 μg/kg per day were well tolerated. Clinical responses were observed at all dose levels. Conclusion: DAB389IL-2 is well tolerated at doses of less than 31 μg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule.
AB - Background: DAB389IL-2 is a novel fusion toxin that retargets the cytotoxic A-chain of diphtheria toxin to interleukin-2 (IL-2) receptor- expressing tumors. Objective: The purpose of this phase I trial was to study the toxicity, maximum tolerated dose, and clinical efficacy of DAB389IL-2 in IL-2 receptor expressing lymphoproliferative malignancies, including cutaneous T-cell lymphoma. Methods: DAB389IL-2 was administered intravenously daily for 5 days every 3 weeks. Dose escalation occurred between patient groups. Patients were monitored for laboratory and clinical toxicity, kinetics, immune response, and clinical efficacy. Results: Thirty- five patients with cutaneous T-cell lymphoma (including 30 patients with mycosis fungoides) were treated. Previously, conventional therapy had not worked for 34 of the patients. Thirteen patients (37%) achieved an objective response, including a complete response in five patients (14%). Complete response was achieved in patients with extensive erythroderma and tumor stage mycosis fungoides. Adverse events consisted of reversible fever/chills, hypotension, nausea/vomiting, and elevation of hepatic transaminase. Doses of less than 31 μg/kg per day were well tolerated. Clinical responses were observed at all dose levels. Conclusion: DAB389IL-2 is well tolerated at doses of less than 31 μg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule.
UR - http://www.scopus.com/inward/record.url?scp=0031594913&partnerID=8YFLogxK
U2 - 10.1016/S0190-9622(98)70403-7
DO - 10.1016/S0190-9622(98)70403-7
M3 - Article
C2 - 9674399
AN - SCOPUS:0031594913
SN - 0190-9622
VL - 39
SP - 63
EP - 73
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 1
ER -