Artículo
Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
Sarduy, M. R.; García, I.; Coca, M. A.; Perera, A.; Torres, L. A.; Valenzuela, C. M.; Baladrón, I.; Solares, M.; Reyes, V.; Hernández, I.; Perera, Y.; Martínez, Y. M.; Molina, L.; González, Y. M.; Ancízar, J. A.; Prats, A.; González, L.; Casacó, C. A.; Acevedo, B. E.; López Saura, P. A.; Alonso, Daniel Fernando
; Gómez, R.; Perea Rodríguez, S. E.
Fecha de publicación:
05/2015
Editorial:
Nature Publishing Group
Revista:
British Journal Of Cancer
ISSN:
0007-0920
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.
Palabras clave:
B23/NUCLEOPHOSMIN
,
CERVICAL CANCER
,
CIGB-300
,
TUMOUR UPTAKE
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Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Sarduy, M. R.; García, I.; Coca, M. A.; Perera, A.; Torres, L. A.; et al.; Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer; Nature Publishing Group; British Journal Of Cancer; 112; 10; 5-2015; 1636-1643
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