Chemotherapy for stomach cancer

Treatment of stomach cancer in the first two stages (less often in the third) is performed surgically. As a rule, chemotherapy is prescribed after surgery. Sometimes antitumor drugs are prescribed before surgery.

Tablets, IVs or injections destroy tumor cells, reduce the risk of metastasis, minimize the number of relapses and prolong the patient's life.

In modern medicine, chemotherapy for stomach cancer is divided into the following areas:

• adjuvant use of pharmacological agents after radical surgery;
• neoadjuvant use of drugs before surgery followed by intraperitoneal therapy;
• Chemotherapy for disseminated gastric cancer.

The aim of the operation is to excise the affected tissues with possible removal of part of the stomach and adjacent lymph nodes to prevent the formation of metastases. The condition of patients with inoperable tumors is improved by palliative surgery.

Taking antitumor drugs before surgery helps reduce the tumor focus and makes the surgery easier. Postoperative chemotherapy reduces the risk of recurrence of cancer cells and the spread of the malignant process to other organs.

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Indications for chemotherapy for stomach cancer

Antitumor therapy is prescribed in the following cases:

• for the purpose of preparation for or in combination with surgical treatment;
• when cancer cells grow onto the inner surface of the peritoneum;
• if metastases are detected in the liver;
• to reduce the size of an inoperable tumor;
• if necessary, alleviate the patient's condition by relieving oncological symptoms.

Indications for chemotherapy for stomach cancer depend on the type of tumor, the stage of the cancer process and the possibility of surgical intervention. In connection with the above, chemotherapy for stomach cancer is divided into:

• independent - prescribed to inoperable patients when it is not possible to remove the tumor, there are multiple metastases or the patient himself refuses the operation. In this case, antitumor drugs improve the patient's quality of life, reducing the negative manifestations of the disease, prolong life, and also inhibit the development of cancer cells and the spread of metastases;
• neoadjuvant and adjuvant (before and after surgery) - in the first case, treatment helps to reduce the area of the pathological lesion and facilitate the course of surgical intervention. The purpose of postoperative drug treatment is to exclude relapse by eliminating micro/macro metastases;
• palliative – recommended for widespread stomach cancer (administered intravenously or using an infusion pump);
• intraperitoneal - an indication for extremely rare exposure is the diagnosis of tumor cells on the inside of the peritoneal cavity in combination with ascites (fluid accumulation). Medicines are delivered directly by catheter, after the liquid contents are removed. Antiemetics are used in parallel;
• pharmacological infusions into the liver artery – necessary when liver metastases are detected. The manipulation, which is considered experimental, is performed under general anesthesia. Such an introduction allows the drugs to be delivered through a small incision in the peritoneum directly to the liver affected by metastases.

Adjuvant chemotherapy for gastric cancer

The main objective of adjuvant chemotherapy is to influence the process of micrometastasis after excision of the primary gastric tumor and macrometastases localized in nearby lymph nodes. The success of treatment is assessed by the median survival and life expectancy indicators among the studied group of patients.

In clinical practice, adjuvant chemotherapy for gastric cancer is a non-standard approach, which is explained by the lack of effective pharmacological drugs and treatment regimens for gastric tumors. Unfortunately, to date, all available combinations of treatment for operable gastric cancer with metastases, when the tumor penetrates beyond the submucosal layer, provide a five-year median survival rate of only 20-30% of cases.

According to randomized trials based on 5-fluorouracil, which were conducted all over the world, it was not possible to identify a clear advantage of the combination treatment. The inability to record differences in survival is explained by the insufficient number of patients in the studied groups. However, data from Japanese scientists indicate that chemotherapy for gastric cancer in the postoperative period improves the three-year survival rate by almost 12%. On the other hand, about 30% of patients were unable to complete 12 months of therapy with oral fluoropyrimidine S1 due to obvious toxicity. According to the results of similar meta-analyses, adjuvant chemotherapy for gastric cancer reduced the overall risk of mortality by an average of 4%.

The need for adjuvant intraperitoneal chemotherapy is due to the number of postoperative relapses in the form of peritoneal metastases. Chemotherapy drugs (5-fluorouracil, cisplatin and mitomycin) are administered via a catheter or by hyperthermic perfusion directly into the abdominal space.

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Chemotherapy course for stomach cancer

In relation to resectable gastric cancer after radical surgery, the tactics of strict dynamic observation have been in effect for a long period. The results of recent international studies indicate that patients with locally advanced gastric cancer, in the absence of contraindications, are recommended to undergo combined treatment in one of the following three options:

• adjuvant therapy - a postoperative course of chemotherapy for gastric cancer, which is introduced 4-6 weeks after surgery in the absence of severe complications and after normalization of clinical and laboratory parameters. The XELOX (CAPOX) program (oral combination of xeloda and oxaliplatin) or FOLFOX (a combination of 5-fluorouracil/leucovorin and intravenous oxaliplatin) is used for six months. If there are contraindications to the use of oxaliplatin, then six-month treatment with capecitabine is possible;
• perioperative therapy – 2-3 courses of polychemotherapy are administered in accordance with the CF (cisplatin + 5-fluorouracil), ECF (epirubicin + cisplatin + 5-fluorouracil) or ECX (epirubicin + cisplatin + capecitabine) regimens. If there are no signs of unresectability, then surgical intervention is indicated with the following 3-4 cycles of similar chemotherapy (6 courses in total);
• postoperative chemoradiation therapy:
  • for 5 days – 5-fluorouracil 425 mg/m2 ^and leucovorin 20 mg/ ^m2;
  • from the 28th day, radiation therapy 45 g (5 days a week for 5 weeks in fractions of 1.8 g) + 5 fluorouracil 400 mg/m2 ^and leucovorin 20 mg/m2 ⁱⁿ the first 4 and last 3 days of radiation therapy;
  • After completion of radiation therapy, a month later, 2 more cycles are carried out: 5-fluorouracil 425 mg/ ^m2 and leucovorin 20 mg/ ^m2 from the 1st to the 5th day with an interval of 28 days.

Chemotherapy regimens for stomach cancer

The choice of antitumor drug program largely depends on the general condition of the patient and the clinical picture. For example, for young patients with a generally satisfactory condition without complications (no bleeding), chemotherapy regimens with platinum MEP are recommended. In the treatment of elderly patients and weakened individuals, ELF chemotherapy regimens for gastric cancer are preferable, which are less toxic and can be carried out in an outpatient setting.

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MEASURE

• mitomycin 5 mg/m2 intravenously on days 1 and 7;
• etoposide 60 mg/m2 intravenously on days 4, 5, 6;
• cisplatin 40 mg/m2 intravenously on days 2 and 8.

Therapeutic courses every 4 weeks.

ELF

• etoposide 120 mg/m2 intravenously on days 1, 2, 3;
• Leucovorin 30 mg/m2 intravenously on days 1, 2, 3;
• 5-fluorouracil 500 mg/m2 intravenously by jet stream on days 1, 2, 3.
• Repeat the treatment course on day 28.

Interest in combinations of irinotecan and taxanes, as well as cisplatin and docetaxel, has grown significantly. Chemotherapy for gastric cancer using the TC and TCF regimens has shown high efficiency.

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TS

• docetaxel 75 mg/m2 intravenously 1 day;
• cisplatin 75 mg/m2 intravenously 1 day.

Repeat treatment every 3 weeks.

TCF

• docetaxel 75 mg/m2 intravenously 1 day;
• cisplatin 75 mg/m2 intravenously 1 day;
• 5-fluorouracil at a daily dose of 750 mg/m2 intravenously by infusion on days 1–5.

Therapeutic course every 3 weeks.

Combinations with fluoropyrimidines are being actively studied, due to their pharmacokinetic properties that imitate the long-term effect of 5-fluorouracil. This discovery allows replacing the tedious for staff and patients infusions of 5-fluorouracil as part of the ECF program with oral administration of capecabin or UFT (depot form of fluorofur and uracil). Capecabin has good absorption rates even in patients with gastric resection.

ECF

• epirubicin 50 mg/m2 intravenously every 3 weeks;
• cisplatin 60 mg/m2 intravenously every 3 weeks;
• 5-fluorouracil at a daily dose of 200 mg/m2 by continuous intravenous infusion for 18–21 weeks.

It should be noted that the successes of antitumor therapy are quite modest, which means there is a need to search for new combinations.

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Chemotherapy drugs for stomach cancer

For a long time, 5-fluorouracil remained the main drug in antitumor therapy, which was replaced by irinotecan, taxanes, and cisplatin. Speaking about the choice of treatment, there is no evidence in clinical practice of the lower effectiveness of chemotherapy with 5-fluorouracil compared to the combined method. Treatment regimens based on several drugs have an objective antitumor effect, but often do not increase life expectancy in proportion to monotherapy with 5-fluorouracil, which can be seen in the table below.

Chemotherapy drugs for stomach cancer and their effectiveness:

Document Without Name

Antitumor drugs	Number of patients	Objective efficiency, %
Antimetabolites: 5fluorouracil Methotrexate Gemcitabine UFT Hydroxyurea (per os) Fluorofur (per os)	416 28 15 188 31 19	21 11 0 28 19 19
Taxanes: Paclitaxel Docetaxel	98 123	17 21
Antibiotics: Mitomycin C Doxorubicin Epirubicin	211 141 80	30 17 19
Platinum derivatives: Cisplatin Carboplatin	139 41	19 5
Topoisomerase inhibitors: Irinotecan Topotecan	66 33	23 6

Chemotherapy for stomach cancer is divided according to the method of delivery of the drug into the body:

• injections;
• use of tablets;
• intravenously via catheter;
• infusion pump (infusion pump).

Chemotherapy after gastrectomy

When metastases grow, gastrectomy or complete removal of the stomach is required. Until recently, patients with metastatic gastric cancer were considered incurable, but studies by German scientists have shown the effectiveness of chemotherapy followed by total resection of the stomach or esophagus and metastases. Treatment was carried out according to the FLOT scheme, which contributed to an increase in life and showed excellent results in the duration of remission. Preoperative chemotherapy for gastric cancer included taking 5-fluorouracil, oxaliplatin and docetaxel.

In case of complete removal of the stomach, the esophagus is connected directly to the small intestine. The recovery period for patients who have undergone such an operation is prolonged until body weight is normalized. The patient will need an optimally selected nutrition system that helps to normalize the process of defecation and replenish the vitamin balance. Chemotherapy after removal of the stomach with the construction of individual therapeutic schemes is used to prevent oncological relapse in the absence of deterioration of the general condition and complications.

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Contraindications to chemotherapy for stomach cancer

There are absolute and relative contraindications to chemotherapy for stomach cancer. The following are contraindications to antitumor drug therapy:

• chronic liver and kidney dysfunction;
• severe forms of infectious diseases;
• mental illness;
• blocked bile ducts;
• deterioration of the patient's general condition;
• non-invasive oncology;
• the conclusion of several specialists about the ineffectiveness of chemotherapy.

Relative contraindications include:

• state of immunodeficiency;
• rheumatoid arthritis;
• patient's age;
• treatment with antibiotics and antiepileptic drugs.

Since chemotherapy for stomach cancer often entails a number of complications and can negatively affect the health of the body as a whole, the attending physician must carefully weigh the pros and cons before starting the course. The final decision is influenced by: the results of laboratory tests and a complete diagnosis of the patient's condition, as well as the presence of pregnancy. During the treatment, it is important to undergo regular examinations in order to have a complete understanding of the effect of antitumor therapy on the body and monitor each stage.

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Side effects of chemotherapy for stomach cancer

In many ways, the side effects of chemotherapy for stomach cancer are due to the drug used and its dosage. Anti-tumor therapy kills cancer, but at the same time, absolutely healthy cells suffer:

• hair follicles - unfortunately, baldness is inevitable. After a course of chemotherapy, hair most often appears again, but the patient should be prepared for changes in their structure, color, etc.;
• blood - when the content of healthy blood cells decreases, infectious lesions are common. Against the background of rapid fatigue and chronic tiredness, bruises and hematomas are instantly formed. During chemotherapy, it is important to monitor the level of blood cells and, if necessary, take a break from taking medications or reduce the dosage with parallel administration of hematopoietic agents;
• walls of the gastrointestinal tract - drug therapy leads to a deterioration in appetite with the appearance of nausea, vomiting, bowel movements, and the formation of ulcers in the mouth and lips.

Chemotherapy for stomach cancer can cause hearing loss, various skin rashes, tingling or numbness in the feet and hands. To normalize the patient's condition, special programs have been developed that are implemented by the attending physician individually in each specific situation.

Complications of chemotherapy for stomach cancer

Antitumor treatment is dangerous due to complications caused by the toxicity of pharmacological agents and individual characteristics of the development of the disease itself. Chemotherapy for gastric cancer is fraught with weight loss, which must be taken into account when developing therapeutic regimens. Active weight loss in the last month or a 10% discrepancy with the initial value are considered negative consequences. Chemotherapy for gastric cancer in this case provokes stomatitis, sepsis, neutropenia, enterocolitis with severe diarrhea. Patients are recommended to prescribe courses of drugs without platinum-containing combinations.

A serious side effect of the drugs is severe or complete dysphagia as a result of stenosis or refusal to eat as a result of food aversion. Chemotherapy can be continued after body weight is restored and all adverse effects are eliminated.

Complications of chemotherapy for gastric cancer include life-threatening bleeding in the case of an unremoved primary tumor or as a result of a relapse at the anastomosis site. To avoid such a dangerous condition, it is necessary to check the hemoglobin level 2-3 times a week. The patient should monitor his condition. If melena (a mass similar to coffee grounds) is detected in the stool or vomiting with blood, promptly notify the attending physician. The medication is stopped, and all efforts of the medical staff are directed at symptomatic hemostatic therapy, including the blood replacement procedure.

Bleeding resulting in tumor disintegration is an indication for gastric resection (palliative gastrectomy).

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Nutrition during chemotherapy for stomach cancer

A great help to the body is a properly organized diet during chemotherapy for stomach cancer, excluding the intake of any animal fats (meat, fish, eggs, lard, sour cream, dairy products, etc.). Preference should be given to fats of plant origin. The ideal option would be olive and linseed oil obtained by cold pressing. You will also have to forget about pastries, cakes, and pies. An alternative would be whole grain porridge and bread (preferably yeast-free) with bran. The table during chemotherapy should be enriched with fresh and raw vegetables, fruits, and greens as much as possible. Restrictions apply to sugar and salt.

Methods of cooking - steamed, boiled, stewed, baked. In addition to fried (including on an open fire), you should avoid smoked, salted and canned foods. The number of meals should reach 5-6 per day, in small portions, to reduce the release of precious energy for digestion and assimilation of food.

Chemotherapy for stomach cancer requires mandatory adherence to a diet:

• replacing meat with legumes (a source of protein that does not require the body to expend resources during the digestion process);
• If you cannot give up fish, eat low-fat varieties of seafood;
• low-fat dairy products are allowed;
• do not eat burnt food;
• exclude coffee-containing drinks and alcohol;
• drink clean water;
• control your weight.

How to restore the stomach after chemotherapy?

Getting rid of intoxication, strengthening the immune system, restoring the functioning of internal organs and systems are the main tasks of complex therapy after taking antitumor drugs. Each patient will need an individual recovery program, including diet, herbal cleansing, juice and aromatherapy, lymphatic drainage, physical exercise (swimming, exercise therapy), etc.

Common complications of chemotherapy are ulcers, gastritis, constipation, dysbacteriosis, candidiasis, diarrhea, nausea, vomiting, etc. Medicines that reduce the sensitivity of the vomiting center are prescribed to prevent vomiting. Bitter medicinal plants (wormwood, gentian, etc.) help stimulate the secretory activity of the stomach. Stool can also be normalized with the help of herbs:

• for diarrhea - bergenia, marsh cinquefoil, galangal;
• for constipation - senna, buckthorn, dill, anise, fennel.

The following few steps show how to restore the stomach after chemotherapy:

• elimination of general intoxication – maintaining a water regime (drinking more water, rosehip/rowan berry decoctions, cranberry/lingonberry juice) and taking diuretic compounds (couch grass root, field horsetail);
• removal of toxic substances from the gastrointestinal tract - for this purpose, activated carbon, zosterin, polyphepan, mucus-secreting herbs (angelica, marshmallow, flax seed) are used;
• correction of dysbacteriosis with simultaneous seeding of microflora - in this case, a combination of marsh wild rosemary with creeping thyme and Icelandic cetraria is irreplaceable. Live strains of lactic acid bacteria are also successfully used.

Properly selected chemotherapy for stomach cancer based on modern drugs (including cytostatic series) allows to avoid most of the disorders in the gastrointestinal tract.