Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

SARDUY MR; GARCIA I; COCA MA; PERERA A; TORRES LA; VALENZUELA CM; BALADRON I; SOLARES M; REYES V; HERNANDEZ I; PERERA Y; MARTINEZ YM; MOLINA L; ANCIZAR JA; PRATS A; GONZALEZ L; CASACO CA; ACEVEDO BE; LOPEZ SAURA P; ALONSO DF; GOMEZ RE; PEREA SE

BRITISH JOURNAL OF CANCER

NATURE PUBLISHING GROUP

Año: 2015 vol. 112 p. 1636 - 1643

0007-0920

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.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.