Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

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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, Gonzalez YM, Ancizar JA, Prats A, Gonzalez L, Casaco CA, Acevedo BE, Lopez-Saura PA, Alonso DF, Gomez R, Perea-Rodriguez SE

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

Br J Cancer. 2015 May 12;112(10):1636-43. doi: 10.1038/bjc.2015.137. Epub 2015 Apr 16.

PubMed ID
25880012 [ View in PubMed
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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. 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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