I. Overview of chemotherapy for gastric cancer
Surgery is still the most effective method to cure gastric cancer, but most patients (60%-70%) have focal metastasis or metastasis to adjacent vital organs before symptoms appear, which makes surgical resection difficult. Therefore, only 30-40% of patients may be cured by surgery alone, with a median survival of 25 months and a 5-year survival rate of about 30%, and most patients die of tumor recurrence or distant metastatic disease. Chemotherapy, as an important means of adjuvant treatment for gastric cancer, has common clinical application, but at present, the overall efficiency of chemotherapy for gastric cancer is low, and it can only be used as adjuvant therapy, i.e., generally as preoperative, intraoperative and postoperative adjuvant treatment for surgery, which can achieve the following purposes.
1.Limit the lesion in order to improve the surgical resection rate.
2.To reduce the chance of tumor cell dissemination and implantation during surgery.
3.Adjuvant chemotherapy after radical surgery to eliminate the possible residual lesions to prevent metastasis and recurrence.
4.After palliative surgery, it can control the disease development and prolong the survival period.
With the in-depth research on gastric cancer and the development of chemotherapeutic drugs, new chemotherapy strategies and new chemotherapeutic drugs have shown their better therapeutic prospects and are being validated through phase III and IV clinics. Another major goal of future clinical research is to obtain markers that can determine prognosis. Thus, adjuvant chemotherapy and neoadjuvant chemotherapy regimens that meet individual differences can be developed. The molecular mechanism of action of antitumor drugs will be studied by biochemical techniques, which may determine the sensitivity of treatment. It is conceivable that with the in-depth understanding of tumor biology, chemotherapy for gastric cancer will be more effective, and the future chemotherapy regimen will be different from individual to individual, and the phenomenon of under-treatment or over-treatment will disappear.
II. The use of chemotherapy
1.Adjuvant chemotherapy to surgery or radiotherapy
At present, adjuvant chemotherapy has received attention because the view of the time of tumor initiation of metastasis is significantly different from that of the past in recent years. In the past, it was believed that the tumor was only a local disease at the beginning, and then it invaded to the surrounding area, first by lymphatic tract metastasis, and finally by bloodway systemic metastasis, so the key to treat the tumor is to remove the tumor completely at an early stage, and the scope of surgery should be extensive. However, in recent years, it has been recognized that after the occurrence of tumor, tumor cells are constantly shed from the tumor body and enter the blood circulation, most of them can be eliminated by the body’s immune defense mechanism, but a small number of un-eliminated tumor cells can become the root cause of recurrence and metastasis, therefore, when the tumor is found clinically and operated, in fact, most patients have distant metastasis. Therefore, after surgery, systemic chemotherapy should be used to eliminate the metastatic microscopic lesions in a timely manner, taking the opportunity that most of the tumors have been removed.
2.Neoadjuvant chemotherapy
Neoadjuvant chemotherapy is adjuvant chemotherapy given before surgery. The duration of adjuvant chemotherapy given before surgery is not too long, usually about 3 courses are given. Its mechanism of action may be different from the 6~12 courses of adjuvant chemotherapy after surgery, so it is not called preoperative adjuvant chemotherapy, but neoadjuvant chemotherapy or induction chemotherapy. The earlier chemotherapy is started, the less chance of developing resistance, so in recent years many tumors such as breast cancer are treated with neoadjuvant chemotherapy.
The advantages of neoadjuvant chemotherapy are.
(1) It can avoid the latent secondary foci in the body and accelerate the growth of tumor within 1~7 days after the removal of the primary foci due to the reduction of the total amount of tumor in the body;
②It can prevent the residual tumor in the body from metastasizing easily after surgery due to the strengthening of coagulation mechanism and immunosuppression;
③Make the tumor cells less vigorous and less likely to spread at the time of surgery, etc. However, it is not sure whether it can improve the long-term survival rate of tumor patients.
3.Intra-abdominal chemotherapy
At present, although the survival rate of gastrointestinal tumors has been improved after radical surgery, the chance of recurrence after surgery is high due to the late diagnosis of most cases, so intraperitoneal chemotherapy is used to reduce intraperitoneal recurrence. When the cancer develops to a certain stage and the lesion involves the plasma membrane, the cancer cells on the plasma membrane surface may be shed and become free cancer cells in the peritoneal cavity, causing intraperitoneal implantation. Pharmacokinetics shows that the concentration of drug administered intraperitoneally is significantly higher than that of systemic administration.
Intraperitoneal chemotherapy should be started intraoperatively or early postoperatively, when the tumor load in the body is the smallest and the proliferation of tumor cells is accelerated accordingly, which is sensitive to chemotherapy; if treatment is delayed, the tumor load is large and the effect of chemotherapy is poor; in addition, intraperitoneal adhesions are loosened during surgery, while new adhesions have not yet been formed, and drugs can easily reach all parts of the abdominal cavity. Intraperitoneal chemotherapy is mainly used for ovarian cancer with tiny residual lesions after resection, gastrointestinal cancer with residual after surgery, or with high risk of recurrence and metastasis, peritoneal mesothelioma, etc. The delivery methods of intraperitoneal chemotherapy include single point puncture delivery method, indwelling catheter method, etc. Complications of intraperitoneal chemotherapy include incisional infection, peritonitis, incisional bleeding, leakage of chemotherapy drugs, etc.
4.Arterial perfusion chemotherapy
Compared with systemic intravenous chemotherapy, arterial perfusion chemotherapy has the following characteristics.
①The local tumor tissue drug concentration is obviously increased, and the systemic body circulation drug concentration is obviously reduced.
②The systemic side effects are significantly reduced, while the local organ drug reactions are relatively heavy.
③The dose of chemotherapeutic drugs used for local perfusion can be greatly increased.
④The efficacy of treatment is significantly improved. Arterial perfusion chemotherapy is administered by inserting a catheter into an artery and infusing chemotherapeutic drugs through the catheter. At present, arterial perfusion chemotherapy is mainly used for the treatment of hepatocellular carcinoma, and the methods of arterial cannulation include open cannulation (via the gastric and duodenal arteries or via the right gastroretinal artery) and trans-femoral artery cannulation. In recent years, the use of subcutaneous perfusion pumps has greatly simplified the operation of arterial perfusion. Complications of arterial perfusion chemotherapy include catheter infection, catheter occlusion, catheter dislodgement, and complications of chemotherapy itself such as liver function impairment and bone marrow suppression.