A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis

Abstract

Study design: 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) studies. 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. Conclusion: Bicarbonate markedly enhances the anticancer activity of TACE.Clinical trail registration: ChiCTR-IOR-14005319.DOI: http://dx.doi.org/10.7554/eLife.15691.001

mTOR Senses Intracellular pH through Lysosome Dispersion from RHEB

“…Large unresectable hepatocellular carcinomas (HCCs) are treated with chemoembolization, a treatment aimed to deliver concentrated chemotherapy and starve cancer cells through embolization but this is of only questionable benefit . Intriguingly, however, a clinical study of unresectable HCC in 57 nonrandomized Chinese patients revealed that the addition of HCO 3 − to chemoembolization markedly improved the objective response rate (ORR) (100% vs 44%) and reduced residual disease volume (RDV) (7% vs 46%) . Importantly, this was subsequently recapitulated in a smaller randomized‐controlled trial of 20 patients (ORR 100% vs 64% and RDV 4% vs 28%).…”

Chromatin accessibility changes are associated with enhanced growth and liver metastasis capacity of acid-adapted colorectal cancer cells

“…Finally, the high tumor selectivity of acidosis compared with healthy tissues which are neutral reminds us that targeting acidosis will be safer than conventional chemotherapy and universal to many kinds of cancers [2]. The results of one recent randomized clinical study were encouraging, showing that bicarbonate markedly enhanced the anticancer activity of transarterial chemoembolization for large hepatocellular carcinoma [32]. This clinical research showed us that targeting the acidic environment might be a promising therapeutic method for cancer therapy.…”

Will cancer cells be defeated by sodium bicarbonate?

“…The addition of sodium bicarbonate to the procedure has greatly improved ORR, from 44% in non-randomized trials and 66% in randomized trials to 100% (Chao et al, 2016). Historically the average ORR for TACE is 35%, and is similar to the ORR observed in the TACE control group.…”

“…In a small randomized control trial, TACE combined with bicarbonate yielded a 100% objective response rate (ORR), a significant improvement from the 63.6% ORR in the TACE alone group (Chao et al, 2016). …”