title: Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.
abstract: 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, AUC24h 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Gynecological service, Center for Medical-Surgical Research, Havana 11300, Cuba.
authors.forename: M R
authors.initials: MR
authors.lastname: Sarduy
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: I
authors.initials: I
authors.lastname: García
authors.affiliation: Direction for Clinical Research, Clinical Investigation Center, Havana 11300, Cuba.
authors.forename: M A
authors.initials: MA
authors.lastname: Coca
authors.affiliation: Direction for Clinical Research, Clinical Investigation Center, Havana 11300, Cuba.
authors.forename: A
authors.initials: A
authors.lastname: Perera
authors.affiliation: Direction for Clinical Research, Clinical Investigation Center, Havana 11300, Cuba.
authors.forename: L A
authors.initials: LA
authors.lastname: Torres
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: C M
authors.initials: CM
authors.lastname: Valenzuela
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: I
authors.initials: I
authors.lastname: Baladrón
authors.affiliation: Gyneco-obstetric Hospital 'Ramón González Coro', Havana 10400, Cuba.
authors.forename: M
authors.initials: M
authors.lastname: Solares
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: V
authors.initials: V
authors.lastname: Reyes
authors.affiliation: Deparment of Development, Isotope Center (CENTIS), Havana 11100, Cuba.
authors.forename: I
authors.initials: I
authors.lastname: Hernández
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: Y
authors.initials: Y
authors.lastname: Perera
authors.affiliation: Gynecological service, Center for Medical-Surgical Research, Havana 11300, Cuba.
authors.forename: Y M
authors.initials: YM
authors.lastname: Martínez
authors.affiliation: Gynecological service, Center for Medical-Surgical Research, Havana 11300, Cuba.
authors.forename: L
authors.initials: L
authors.lastname: Molina
authors.affiliation: Gynecological service, Center for Medical-Surgical Research, Havana 11300, Cuba.
authors.forename: Y M
authors.initials: YM
authors.lastname: González
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: J A
authors.initials: JA
authors.lastname: Ancízar
authors.affiliation: Direction for Clinical Research, Clinical Investigation Center, Havana 11300, Cuba.
authors.forename: A
authors.initials: A
authors.lastname: Prats
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: L
authors.initials: L
authors.lastname: González
authors.affiliation: Direction for Clinical Research, Clinical Investigation Center, Havana 11300, Cuba.
authors.forename: C A
authors.initials: CA
authors.lastname: Casacó
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: B E
authors.initials: BE
authors.lastname: Acevedo
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: P A
authors.initials: PA
authors.lastname: López-Saura
authors.affiliation: Molecular Oncology Laboratory, National University of Quilmes, Buenos Aires, Argentina.
authors.forename: D F
authors.initials: DF
authors.lastname: Alonso
authors.affiliation: ELEA Laboratories, Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Gómez
authors.affiliation: CIGB-300 Research and Development Group, Laboratory of Molecular Oncology, Biomedical Research Department, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31 b/158 and 190, Cubanacán, Playa, PO Box 6162, Havana 11300, Cuba.
authors.forename: S E
authors.initials: SE
authors.lastname: Perea-Rodríguez
mesh_terms: D000328:Adult; D019540:Area Under Curve; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D015552:Injections, Intralesional / Q000379:methods; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010456:Peptides, Cyclic; D000090243:Nucleophosmin; C532510:CIGB-300