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 D F, Gómez R, Perea-Rodríguez S E
Gynecological service, Center for Medical-Surgical Research, Havana 11300, Cuba.
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.
Br J Cancer. 2015 May 12;112(10):1636-43. doi: 10.1038/bjc.2015.137. Epub 2015 Apr 16.
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.
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.
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.
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.
我们对局部晚期宫颈癌患者进行了一项1期试验，通过在肿瘤的两个不同部位注射0.5毫升CK2拮抗剂CIGB - 300来评估肿瘤摄取、安全性、药效学活性并确定推荐剂量。
14名患者在标准放化疗前，连续三天为一个周期，共三个交替周期，接受瘤内注射含35或70毫克CIGB - 300的药物。使用（99）Tc放射性标记肽测定肿瘤摄取。通过免疫组织化学测定原位B23/核磷蛋白。
CIGB - 300 70毫克剂量的最大肿瘤摄取显著高于35毫克剂量：分别为16.1±8.9毫克与31.3±12.9毫克（P = 0.01）。使用70毫克CIGB - 300时，AUC24h和生物半衰期也显著更高（P < 0.001）。未结合的CIGB - 300迅速扩散到血液中，主要分布到肾脏，在肝脏、肺、心脏和脾脏中的分布较少。未出现剂量限制性毒性（DLT），中度过敏样反应是最常见的全身副作用，未结合的CIGB - 300与血液中的组胺水平之间存在强相关性。70毫克CIGB - 300可下调肿瘤标本中的B23/核磷蛋白（P = 0.03）。
建议在2期研究中评估在两个部位（每次注射0.5毫升）瘤内注射70毫克CIGB - 300以及该治疗方案。
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