التفاصيل البيبلوغرافية
| العنوان: |
Phase I trial of systemic intravenous infusion of interleukin-13- Pseudomonas exotoxin in patients with metastatic adrenocortical carcinoma. |
| المؤلفون: |
Liu‐Chittenden, Yi, Jain, Meenu, Kumar, Parag, Patel, Dhaval, Aufforth, Rachel, Neychev, Vladimir, Sadowski, Samira, Gara, Sudheer K., Joshi, Bharat H., Cottle‐Delisle, Candice, Merkel, Roxanne, Yang, Lily, Miettinen, Markku, Puri, Raj K., Kebebew, Electron |
| المصدر: |
Cancer Medicine; Jul2015, Vol. 4 Issue 7, p1060-1068, 9p |
| مصطلحات موضوعية: |
ADRENAL cortex, INTERLEUKIN-13, CYTOTOXINS, PSEUDOMONAS toxins, EXOTOXIN, PHARMACOKINETICS, THROMBOCYTOPENIA, CANCER |
| مستخلص: |
Adrenocortical carcinoma ( ACC) is a rare but lethal malignancy without effective current therapy for metastatic disease. IL-13- PE is a recombinant cytotoxin consisting of human interleukin-13 ( IL-13) and a truncated form of Pseudomonas exotoxin A ( PE). The main objectives of this Phase I dose-escalation trial were to assess the maximum-tolerated dose ( MTD), safety, and pharmacokinetics ( PK) of IL-13- PE in patients with metastatic ACC. Eligible patients had confirmed IL-13 receptor alpha 2 ( IL-13R α2) expressions in their tumors. IL-13- PE at dose of 1-2 μg/kg was administered intravenously ( IV) on day 1, 3, and 5 in a 4-week cycle. Six patients received 1 μg/kg and two patients received 2 μg/kg of IL-13- PE. Dose-limiting toxicity was observed at 2 μg/kg, at which patients exhibited thrombocytopenia and renal insufficiency without requiring dialysis. PK analysis demonstrated that at MTD, the mean maximum serum concentration ( Cmax) of IL-13- PE was 21.0 ng/mL, and the terminal half-life of IL-13- PE was 30-39 min. Two (25%) of the eight patients had baseline neutralizing antibodies against PE. Three (75%) of the remaining four tested patients developed neutralizing antibodies against IL-13- PE within 14-28 days of initial treatment. Of the five patients treated at MTD and assessed for response, one patient had stable disease for 5.5 months before disease progression; the others progressed within 1-2 months. In conclusion, systemic IV administration of IL-13- PE is safe at 1 μg/kg. All tested patients developed high levels of neutralizing antibodies during IL-13- PE treatment. Use of strategies for immunodepletion before IL-13- PE treatment should be considered in future trials. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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