Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

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 tr...

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Detalles Bibliográficos
Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/96176
Acceso en línea:http://hdl.handle.net/11336/96176
Access Level:acceso abierto
Palabra clave:B23/NUCLEOPHOSMIN
CERVICAL CANCER
CIGB-300
TUMOUR UPTAKE
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
Descripción
Sumario: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.

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