A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis.
A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis.
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通过针对瘤内乳酸酸中毒局部控制大肝癌的非随机队列和随机研究
作者：
Chao M;Wu H;Jin K;Li B;Wu J;Zhang G;Yang G;Hu X
背景：以往的研究表明，中和瘤内乳酸酸中毒联合葡萄糖剥夺可能是控制肿瘤的有效途径。我们进行了一项试点临床研究，包括一项非随机（57例大型HCC患者）和一项随机对照（20例大型HCC患者）研究。方法：采用经动脉化疗栓塞术（TACE），局部输注碳酸氢盐或不输注碳酸氢盐。结果：在非随机对照研究中，碳酸氢盐TACE组的活肿瘤残留几何平均值（VTR）比不含碳酸氢盐的TACE组低6.4倍（7.1% [95% CI: 4.6%-10.9%] vs 45.6% [28.9%-72.0%]; p<0.0001）。这一差异在随后的随机对照研究中得到了再现。TACE联合碳酸氢盐治疗的客观缓解率（ORR）为100%，而单独TACE治疗的ORR为44.4%（非随机）和63.6%（随机）。生存数据提示碳酸氢盐可能带来生存益处。结论：碳酸氢盐能显著增强TACE的抗癌活性。项目资助：国家自然科学基金资助。临床试验号：ChiCTR-IOR-14005319。
Background: Previous works suggested that neutralizing intratumoral lactic acidosis combined with glucose deprivation may deliver an effective approach to control tumor. We did a pilot clinical investigation, including a nonrandomized (57 patients with large HCC) and a randomized controlled (20 patients with large HCC) study. Methods: The patients were treated with transarterial chemoembolization (TACE) with or without bicarbonate local infusion into tumor. Results: In the nonrandomized controlled study, geometric mean of viable tumor residues (VTR) in TACE with bicarbonate was 6.4-fold lower than that in TACE without bicarbonate (7.1% [95% CI: 4.6%–10.9%] vs 45.6% [28.9%–72.0%]; p<0.0001). This difference was recapitulated by a subsequent randomized controlled study. TACE combined with bicarbonate yielded a 100% objective response rate (ORR), whereas the ORR treated with TACE alone was 44.4% (nonrandomized) and 63.6% (randomized). The survival data suggested that bicarbonate may bring survival benefit. Conclusions: Bicarbonate markedly enhances the anticancer activity of TACE. Funding: Funded by National Natural Science Foundation of China. Clinical trial number: ChiCTR-IOR-14005319.