Ascorbic acid + Sorafenib

The combination of ascorbic acid (Vitamin C) and sorafenib is a potential therapeutic approach investigated for treating hepatocellular carcinoma (HCC) or liver cancer. Preclinical studies indicate a synergistic effect between ascorbic acid and sorafenib in killing liver cancer cells (Hep G2) while sparing primary hepatocytes, suggesting potential to broaden sorafenib's therapeutic range. **Mechanism of Synergy:** The synergy involves several mechanisms: 1. **H2O2 Generation**: Ascorbic acid generates hydrogen peroxide (H2O2), which contributes to its cytotoxic effect on cancer cells. 2. **Calcium Homeostasis Disruption**: The combination treatment significantly disrupts cellular calcium homeostasis. 3. **Mitochondrial Effects**: Sorafenib causes mitochondrial depolarization and prevents mitochondrial calcium sequestration. When combined with ascorbic acid, which leads to mitochondrial calcium accumulation, the disruption of cellular calcium homeostasis is enhanced, promoting cancer cell death. **Clinical Investigation:** A Phase I/II clinical trial (NCT01754987) has evaluated the safety and efficacy of intravenous ascorbic acid infusions combined with sorafenib versus sorafenib alone in patients with metastatic HCC. The trial design included a Phase I portion to assess safety and efficacy in a small group and a randomized Phase II portion comparing the combination to sorafenib alone. The trial aimed to assess safety, tolerability, overall tumor response rate, and disease progression. **Potential Benefits:** The combination therapy may offer: * Enhanced cytotoxicity against cancer cells. * Potential to overcome drug resistance. * Possible reduction in sorafenib side effects. * Broader therapeutic range for sorafenib. A case report suggests clinical relevance, showing prolonged regression of a rib metastasis in an HCC patient treated with this combination. Similar synergistic effects with vitamin C have been noted with other targeted therapies for HCC, such as lenvatinib, indicating potential broader applicability for enhancing tyrosine kinase inhibitor efficacy in liver cancer.

Other names

Vitamin C + Sorafenib