Liver cancer treatment in 2023

Burden of liver cancer

Liver cancer is a common malignant tumor accounting for more than half of the global liver cancer. The onset of hepatocellular carcinoma (HCC) is hidden, and early symptoms are not obvious. Most people have lost the opportunity for surgery at the time of treatment. Whether it is surgery, interventional therapy or chemotherapy, the treatment effect on liver cancer is still not very satisfactory. The survival rate is still very low.

With the development of science and technology, liver cancer targeted drugs have made great progress, and a variety of targeted drugs and immunotherapy drugs have been approved, bringing new hope to the long-term survival of liver cancer patients!

Liver Cancer Chemotherapy

Chemotherapy is treatment with drugs to destroy cancer cells. Systemic chemotherapy uses anti-cancer drugs that are injected intravenously or orally. These drugs enter the bloodstream and reach all areas of the body, making this treatment potentially useful for cancers that have spread to distant organs.

However, liver cancer is resistant to most chemotherapy drugs. The most effective drugs for systemic chemotherapy in liver cancer are doxorubicin (doxorubicin), 5-fluorouracil and cisplatin. But even these drugs will only shrink a small part of the tumor, and the response usually does not last long. Even with a combination of drugs, in most studies, systemic chemotherapy did not help patients live longer.

Transcatheter hepatic artery infusion chemotherapy due to poor response to systemic chemotherapy, doctors study placing chemotherapy drugs directly into the hepatic artery for treatment. This technique is called transcatheter hepatic artery infusion chemotherapy, and continuous infusion of anticancer drugs is suitable for hepatic artery intubation For the treatment of liver cancer patients who can not be resected or undergo palliative resection, because the blood supply of liver cancer mainly comes from the arteries, this method can make the drug directly act on the tumor tissue, increase the local drug concentration, reduce the systemic response, and achieve the treatment of the tumor and relieve the symptoms And the purpose of prolonging life.

Compared with systemic chemotherapy, transcatheter hepatic artery infusion chemotherapy is more effective, but does not increase side effects. The most commonly used drugs include fluorouracil, cisplatin, mitomycin C and doxorubicin.

Drugs approved for targeted therapy of liver cancer

Sorafenib (Sorafenib, Dorjemi) ,

Sorafenib is a targeted drug with two effects. One is to prevent the new blood vessels needed for tumor growth, and it can also target proteins that promote the growth of cancer cells. The main targets are VEGFR-1 / 2/3, RET, FLT3, BRAF and so on.

Sorafenib can directly inhibit the proliferation of tumor cells, and can also act on VEGFR and PDGFR to inhibit the formation of new blood vessels and cut off the nutritional supply of tumor cells, thereby curbing tumor growth. Sorafenib is suitable for the first-line treatment of advanced liver cancer that cannot be operated or metastasized.

Sorafenib is an oral medicine, twice a day. The most common side effects of this medication include fatigue of the palms or soles, rash, loss of appetite, diarrhea, high blood pressure, redness, pain, swelling or blisters. Serious side effects (uncommon) include problems with blood flow to the heart and perforation of the stomach or intestines.

regorafenib (Regofenib, Baivango),

Regefenib can block tumor angiogenesis, and can also target several proteins on the surface of cancer cells to prevent the growth of cancer cells. It is an oral multi-target kinase inhibitor that can inhibit VEGFR-1, 2, 3, TIE-2, BRAF, KIT, RET, PDGFR and FGFR, and its structure is similar to sorafenib.

On December 12, 2017, the State Food and Drug Administration (CFDA) approved the oral multi-kinase inhibitor regorafenib for patients with hepatocellular carcinoma (HCC) who had previously been treated with sorafenib. Take it orally once a day for 3 consecutive weeks, then rest for a week, and then continue to the next cycle.

Common side effects of chemotherapy

Common side effects include fatigue, loss of appetite, hand and foot syndrome (redness and irritation of hands and feet), high blood pressure, fever, infection, weight loss, diarrhea and abdominal (abdominal) pain. Serious side effects (uncommon) may include severe liver damage, severe bleeding, heart blood flow problems, and perforation of the stomach or intestines.

lenvatinib (Levatinib, Levira)

Lenvatinib is a multi-targeted drug. The main targets of levatinib include vascular endothelial growth factor receptor VEGFR1-3, fibroblast growth factor receptor FGFR1-4, platelet-derived growth factor receptor PDGFR-α, cKit, Ret et al. Work by preventing tumors from forming new blood vessels that need to grow.

In August this year, Eisai (Eisai) and Merck (MSD) lovastinib were approved by the US FDA for marketing. Leweima was included in the first-line treatment of non-surgical advanced liver cancer by the CSCO liver cancer guideline (2018 version), China’s most authoritative tumor diagnosis and treatment guideline.

Lenvatinib is administered orally once daily. The most common side effects of this medication are palmar-footed redness syndrome, skin rash, loss of appetite, diarrhea, high blood pressure, joint or muscle pain, weight loss, abdominal pain or blisters. Serious side effects (uncommon) may include bleeding problems and loss of protein in the urine.

Cabozantinib

Cabozantinib (Cabozantinib) is a small-molecule multi-target inhibitor developed by Exelixis of the United States, which can target VEGFR, MET, NTRK, RET, AXL and KIT. It has a name better known to the majority of patients, ” XL184 “.

On May 29, 2018, the FDA approved Carbotinib for second-line treatment of advanced liver cancer. Approval is based on the phase III clinical trial CELESTIAL. Patients with advanced hepatocellular carcinoma who have progressed after sorafenib treatment have significantly improved overall survival compared with placebo. Progression-free survival and objective response rate have also improved significantly.

Larotinib, a broad-spectrum anticancer drug

On November 26, 2018, the legendary anticancer drug larotrectinib (Vitrakvi, Larotinib, LOXO-101) was finally approved by the FDA for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors with NTRK gene fusion . Regardless of the type of cancer, as long as it is a solid tumor positive for genetic testing for NTRK fusion, this broad-spectrum targeted drug can be used!

In some rare cancers, NTRK fusion often occurs. These include infantile fibrosarcoma, secretory breast cancer, etc. These rare cancers usually find NTRK fusion, and these patients may benefit from drugs such as larotrectinib. This targeted drug is not only effective, but also a broad-spectrum anti-cancer drug, effective for many different tumors! This is why this medicine is so eye-catching.

In the experiment, these patient tumor types included 10 different soft tissue sarcomas, salivary adenocarcinoma, infantile fibrosarcoma, thyroid cancer, lung cancer, melanoma, colorectal cancer, gastrointestinal stromal tumor (GIST), breast cancer, osteosarcoma , Cholangiocarcinoma, primary unknown cancer, congenital mesoderm kidney cancer, appendix and pancreatic cancer.

In addition, advanced cancer patients who have undergone cancer genome testing may find that their tumors have NTRK fusion, because NTRK gene fusion can occur in various cancer tissues, including liver cancer.

General inspection of fusion genes requires the use of second-generation genetic testing technology. And it must be noted that the mutation of NTRK gene fusion with other genes, rather than a random point mutation.

The world’s top genetic testing companies Kerris and Foundation Medicine also recently devel
oped Foundation One CDx for NTRK fusion testing. Patients who want to know can call the Medical Department of the Global Oncologist Network for consultation (400-626-9916).

Liver cancer drugs in research

① Everolimus

It is a selective inhibitor of mTOR. MTOR is a key serine-threonine kinase. Everolimus can combine with intracellular protein FKBP12 to form an inhibitory complex mTORC1. It can produce anti-tumor purposes by interfering with cell cycle and angiogenesis. .

However, the results of the current clinical trials suggest that Everolimus is not effective in the treatment of patients with advanced HCC, and its clinical value as a second-line drug therapy still needs to be further discussed.

②Bevacizumab

It is the first anti-angiogenic drug approved by the FDA for clinical use. It is a recombinant human IgG-1 monoclonal antibody against VEGF. It can prevent VEGF from binding to VEGFR by binding to VEGF and inhibit the proliferation and activation of vascular endothelial cells. , Thereby exerting anti-angiogenesis and anti-tumor effects. Current research shows that bevacizumab alone or combined chemotherapy or other targeted drugs are effective in the treatment of liver cancer.

③Apatinib

Apatinib is the world’s first small molecule anti-angiogenesis targeted drug that has been proven to be safe and effective in advanced gastric cancer. It is also a single drug that significantly prolongs survival after standard chemotherapy for advanced gastric cancer fails. It is also a self-developed anti-cancer targeted drug in China, which has achieved certain effects in liver cancer, gastric cancer, non-small cell lung cancer and breast cancer, and has been included in medical insurance.

Aitan (Apatinib) is through highly selective competition for intracellular VEGFR-2 ATP binding site, blocking downstream signal transduction, thereby potently anti-tumor tissue angiogenesis, and ultimately achieve the goal of combating tumors in all directions.

Drugs approved for liver cancer immunotherapy

Immunotherapy drugs help the body’s immune system attack cancer cells by targeting the PD-1 / PD-L1 cell signaling pathway (PD-1 and PD-L1 are proteins that are present in the body’s immune cells and certain cancer cells). In layman’s terms: By blocking the binding of PD-L1 protein to cancer cells, the camouflage of cancer cells is prevented, and the body’s own immune cells can recognize and eliminate cancer cells.

Pembrolizumab (Pembrolizumab, Keytruda) and Nivolumab (Nivolumab, Opdivo) are drugs targeting PD-1. By blocking PD-1, these drugs can enhance the immune response to cancer cells. This can shrink some tumors or slow their growth. These drugs can be used in patients with liver cancer who have previously undergone treatment with the targeted drug sorafenib (dojime).

Pembrolizumab (Pembrolizumab, Keytruda)

On November 9, 2018, the