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  MONOCLONAL ANTIBODIES FOR IN VIVO APPLICATIONS - PART I


Minerva Biotecnologica 1998 September;10(3):100-7

Copyright © 1998 EDIZIONI MINERVA MEDICA

lingua: Inglese

Intraperitoneal radio­im­mu­no­ther­a­py for refrac­to­ry epi­the­lial ovar­ian can­cer ­with 177Lu-CC49

Meredith R., Alvarez R., Khazaeli M. B., Lo Buglio A.

University of Alabama Comprehensive Cancer Center, University of Alabama at Birmingham, USA


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Background. To devel­op sal­vage ther­a­py for per­sis­tent/recur­rent ovar­ian can­cer con­fined to the abdom­i­nal cav­ity ­after stan­dard treat­ment.
Methods. High-affin­ity ­anti-TAG-72 anti­body CC49 radio­lab­eled ­with 177Lu was giv­en via intra­per­it­o­neal (IP) admin­is­tra­tion as a sin­gle ­agent or ­with ­human recom­bi­nant inter­fer­on ­alpha(sub­cu­ta­ne­ous)±IP Taxol. IP admin­is­tra­tion for per­i­to­neal ­implants con­fined to the abdom­i­nal cav­ity has the advan­tage of high­er con­cen­tra­tion of ­active ­agent at ­tumor ­deposits ­with ­less tox­ic­ity to the ­bone mar­row ­from ­system absorp­tion. Eligible ­patients had TAG-72 express­ing tumor lim­it­ed to the abdom­i­nal cav­ity ­after lap­a­rot­o­my-chem­o­ther­a­py, ­ECOG per­for­mance stat­us ≤2, ade­quate ­organ func­tion and ­free ­flow of ­fluid in the per­i­to­neal cav­ity.
Results. IP 177Lu-CC49 ­alone was ­well tol­er­at­ed in 27 ­patients ­with the ­only Grade 3-4 tox­ic­ity ­being tran­sient ­bone mar­row sup­pres­sion (­dose lim­it­ing at 45 mCi/m2). Tumor/mar­row radi­a­tion ratios ­of 58-139 ­were ­obtained. One of 12 ­patients ­with ­gross dis­ease mea­sur­able by CT had an objec­tive ­response and 3 patients ­with ­small vol­ume dis­ease ­have ­remained with­out evi­dence of ­relapse at 3+-5+ ­years. More objec­tive respons­es ­have ­been not­ed with adju­vant inter­fer­on ±Taxol. Observation con­tin­ues in ­order to deter­mine if ­there ­will be an improve­ment in ­relapse ­free sur­vi­val for ­patients ­with non-mea­sur­able dis­ease ­when adju­vant inter­fer­on+Taxol are ­used.
Conclusions. Intraperitoneal radio­im­mu­no­ther­a­py ­with 177Lu-CC49 ­alone or ­with adju­vant inter­fer­on ± Taxol has ­shown ­anti-­tumor effi­ca­cy and extend­ed ­relapse ­free sur­vi­val in ­patients who ­have ­failed stan­dard ther­a­py.

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