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 microg/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 microg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule.
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 microg/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 microg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule.
Authors: Janet Y Li; Steven Horwitz; Alison Moskowitz; Patricia L Myskowski; Melissa Pulitzer; Christiane Querfeld Journal: Cancer Manag Res Date: 2012-03-12 Impact factor: 3.989
Authors: T Illidge; C Chan; N Counsell; S Morris; J Scarisbrick; D Gilson; B Popova; P Patrick; P Smith; S Whittaker; R Cowan Journal: Br J Cancer Date: 2013-10-17 Impact factor: 7.640