A Phase I Clinical Trial of CHT-25 a 131I-Labeled Chimeric Anti-CD25 Antibody Showing Efficacy in Patients with Refractory Lymphoma
| Autor: | Philip Ross, Peter Amlot, Pei-San Chan, Christopher McNamara, Alan G. Ramsay, T. Andrew Lister, Alessandra Malaroda, Surinder K. Sharma, John R. Buscombe, Anmol Malhotra, Shokri Othman, Richard H. J. Begent, John Violet, Gairin Dancey, Roslyn J. Francis, Nicholas Woodward, Sweta Parker, Alan J. Green, Natalie Griffin |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
medicine.medical_specialty Pathology medicine.diagnostic_test Side effect business.industry medicine.medical_treatment Phases of clinical research Neutropenia medicine.disease Gastroenterology Lymphoma Leukemia Oncology Refractory Positron emission tomography Radioimmunotherapy Internal medicine medicine business |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 15(24) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: There is a need for new treatments for Hodgkin and T-cell lymphoma due to the development of drug resistance in a proportion of patients. This phase I study of radioimmunotherapy used CHT-25, a chimeric antibody to the α-chain of the interleukin-2 receptor, CD25, conjugated to iodine-131 (131I) in patients with refractory CD25-positive lymphomas.Experimental Design: Fifteen patients were treated (Hodgkin lymphoma, 12; angioimmunoblastic T-cell lymphoma, 1; adult T-cell leukemia/lymphoma, 2). Tumor was monitored by computed tomography and in all but two patients by 18F-fluorodeoxyglucose positron emission tomography.Results: There were no grade 3 or 4 infusion reactions. At the maximum tolerated dose of 1,200 MBq/m2, the major side effect was delayed myelotoxicity with the nadir for platelets at 38 days and for neutrophils at 53 days. One patient treated with 2,960 MBq/m2 developed prolonged grade 4 neutropenia and thrombocytopenia and died of Pneumocystis jiroveci pneumonia. Nonhematologic toxicity was mild. Single photon emission computer tomography imaging showed tumor-specific uptake and retention of 131I and no excessive retention in normal organs. Of nine patients receiving ≥1,200 MBq/m2, six responded (three complete response and three partial response); one of six patients with administered radioactivity of ≤740 MBq/m2 had a complete response.Conclusions: CHT-25 is well tolerated with 1,200 MBq/m2 administered radioactivity and shows clinical activity in patients who are refractory to conventional therapies. Phase II studies are justified to determine efficacy and toxicity in a broader range of clinical scenarios. (Clin Cancer Res 2009;15(24):7701–10) |
| Databáze: | OpenAIRE |
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