A Phase I Trial of Radioimmunotherapy with 131I-A5B7 Anti-CEA Antibody in Combination with Combretastatin-A4-Phosphate in Advanced Gastrointestinal Carcinomas. Export

@article{citeulike:4971619, abstract = {PURPOSE: In preclinical models, radioimmunotherapy with (131)I-A5B7 anti-carcinoembryonic antigen (CEA) antibody ((131)I-A5B7) combined with the vascular disruptive agent combretastatin-A4-phosphate (CA4P) produced cures unlike either agent alone. We conducted a phase I trial determining the dose-limiting toxicity (DLT), maximum tolerated dose, efficacy, and mechanism of this combination in patients with gastrointestinal adenocarcinomas.EXPERIMENTAL DESIGN: Patients had CEA of 10 to 1,000 microg/L, QTc </=450 ms, no cardiac arrhythmia/ischaemia, and adequate hematology/biochemistry. Tumor was suitable for blood flow analysis by dynamic contrast enhanced-magnetic resonance imaging (MRI). The starting dose was 1,800 MBq/m(2) of (131)I-A5B7 on day 1 and 45 mg/m(2) CA4P given 48 and 72 hours post-(131)I-A5B7, then weekly for up to seven weeks.RESULTS: Twelve patients were treated, with mean age of 63 years (range, 32-77). Two of six patients at the first dose level had DLTs (grade 4 neutropenia). The dose was reduced to 1,600 MBq/m(2), and CA4P escalated to 54 mg/m(2). Again, two of six patients had DLTs (neutropenia). Of ten assessable patients, three had stable disease and seven had progressive disease. Single-photon emission computed tomography confirmed tumor antibody uptake in all 10 patients. DCE-MRI confirmed falls in kinetic parameters (K(trans)/IAUGC60) in 9 of 12 patients. The change of both pharmacokinetic parameters reached a level expected to produce efficacy in one patient who had a minor response on computed tomography and a reduced serum tumor marker level.CONCLUSIONS: This is believed to be the first trial reporting the combination of radioimmunotherapy and vascular disruptive agent; each component was shown to function, and myelosuppression was dose-limiting. Optimal dose and timing of CA4P, and moderate improvements in the performance of radioimmunotherapy seem necessary for efficacy.}, author = {Meyer, Tim and Gaya, Andrew M. and Dancey, Gairin and Stratford, Michael R. and Othman, Shokri and Sharma, Surinder K. and Wellsted, David and Taylor, Jane J. and Stirling, James J. and Poupard, Linda and Folkes, Lisa K. and Chan, Pei-San S. and Pedley, Barbara B. and Chester, Kerry A. and Owen, Karen and Violet, John A. and Malaroda, Alessandra and Green, Alan J. and Buscombe, John and Padhani, Anwar R. and Rustin, Gordon J. and Begent, Richard H.}, citeulike-article-id = {4971619}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-09-0035}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19549771}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19549771}, day = {23}, doi = {10.1158/1078-0432.CCR-09-0035}, issn = {1078-0432}, journal = {Clinical cancer research}, keywords = {cancer, gastrointestinal}, month = {June}, posted-at = {2009-06-26 12:05:00}, priority = {5}, title = {A Phase I Trial of Radioimmunotherapy with 131I-A5B7 Anti-CEA Antibody in Combination with Combretastatin-A4-Phosphate in Advanced Gastrointestinal Carcinomas.}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-09-0035}, year = {2009} }

TY - JOUR ID - citeulike:4971619 L3 - citeulike-article-id:4971619 N2 - PURPOSE: In preclinical models, radioimmunotherapy with (131)I-A5B7 anti-carcinoembryonic antigen (CEA) antibody ((131)I-A5B7) combined with the vascular disruptive agent combretastatin-A4-phosphate (CA4P) produced cures unlike either agent alone. We conducted a phase I trial determining the dose-limiting toxicity (DLT), maximum tolerated dose, efficacy, and mechanism of this combination in patients with gastrointestinal adenocarcinomas.EXPERIMENTAL DESIGN: Patients had CEA of 10 to 1,000 microg/L, QTc </=450 ms, no cardiac arrhythmia/ischaemia, and adequate hematology/biochemistry. Tumor was suitable for blood flow analysis by dynamic contrast enhanced-magnetic resonance imaging (MRI). The starting dose was 1,800 MBq/m(2) of (131)I-A5B7 on day 1 and 45 mg/m(2) CA4P given 48 and 72 hours post-(131)I-A5B7, then weekly for up to seven weeks.RESULTS: Twelve patients were treated, with mean age of 63 years (range, 32-77). Two of six patients at the first dose level had DLTs (grade 4 neutropenia). The dose was reduced to 1,600 MBq/m(2), and CA4P escalated to 54 mg/m(2). Again, two of six patients had DLTs (neutropenia). Of ten assessable patients, three had stable disease and seven had progressive disease. Single-photon emission computed tomography confirmed tumor antibody uptake in all 10 patients. DCE-MRI confirmed falls in kinetic parameters (K(trans)/IAUGC60) in 9 of 12 patients. The change of both pharmacokinetic parameters reached a level expected to produce efficacy in one patient who had a minor response on computed tomography and a reduced serum tumor marker level.CONCLUSIONS: This is believed to be the first trial reporting the combination of radioimmunotherapy and vascular disruptive agent; each component was shown to function, and myelosuppression was dose-limiting. Optimal dose and timing of CA4P, and moderate improvements in the performance of radioimmunotherapy seem necessary for efficacy. JF - Clinical cancer research SN - 1078-0432 TI - A Phase I Trial of Radioimmunotherapy with 131I-A5B7 Anti-CEA Antibody in Combination with Combretastatin-A4-Phosphate in Advanced Gastrointestinal Carcinomas. KW - cancer KW - gastrointestinal AU - Meyer, Tim AU - Gaya, Andrew AU - Dancey, Gairin AU - Stratford, Michael AU - Othman, Shokri AU - Sharma, Surinder AU - Wellsted, David AU - Taylor, Jane AU - Stirling, James AU - Poupard, Linda AU - Folkes, Lisa AU - Chan, Pei-San AU - Pedley, Barbara AU - Chester, Kerry AU - Owen, Karen AU - Violet, John AU - Malaroda, Alessandra AU - Green, Alan AU - Buscombe, John AU - Padhani, Anwar AU - Rustin, Gordon AU - Begent, Richard PY - 2009/06/23/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-09-0035 ER -