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.
Keywords: bicarbonate; cancer biology; hepatocellular carcinoma; human; lactic acidosis; transarterial chemoembolization.
Surgery is the main treatment for liver cancer, but the most common liver cancer – called hepatocellular carcinoma – can sometimes become too large to remove safely. An alternative option to kill the tumor is to block its blood supply via a process called embolization. This procedure deprives the tumor cells of oxygen and nutrients such as glucose. However, embolization also prevents a chemical called lactic acid – which is commonly found around tumors – from being removed. Lactic acid actually helps to protect cancer cells and also aids the growth of new blood vessels, and so the “trapped” lactic acid may reduce the anticancer activity of embolization. Previous works suggested that neutralizing the acidic environment in a tumor while depriving it of glucose via embolization could become a new treatment option for cancer patients. Chao et al. now report a small clinical trial that tested this idea and involved patients with large hepatocellular carcinomas. First, a group of thirty patients received the embolization treatment together with an injection of bicarbonate – a basic compound used to neutralize the lactic acid – that was delivered directly to the tumor. The neutralization killed these large tumors more effectively than what is typically seen in patients who just undergo embolization Chao et al. then recruited another twenty patients and randomly assigned them to receive either just the embolization or the embolization with bicarbonate treatment. This randomized trial showed that the tumors died more and patients survived for longer if they received the bicarbonate together with the embolization treatment compared to those patients that were only embolized. In fact, four patients initially assigned to, and treated in, the embolization-only group subsequently asked to cross over to, and indeed received, the bicarbonate treatment as well. These data indicate that this bicarbonate therapy may indeed be effective for patients with large tumors that are not amenable to surgery. In future, larger clinical trials will need to be carried out to verify these initial findings.