Chemotherapy for Stomach Cancers

Being diagnosed with stomach (or gastric) cancer can be a life-altering event that comes with a lot of uncertainty. If you are currently discussing treatment options with your cancer care team, they may recommend chemotherapy as part of your treatment plan. Understanding how chemotherapy works is crucial, as it can brace you for what to expect during treatment. Additionally, knowing what to expect can help mentally and emotionally prepare you for the treatment process. During treatment, it is also helpful to have an open and continuous conversation with your doctors to stay on top of medical discussions.

Chemotherapy is a type of treatment that uses cancer-killing drugs to stop or slow the uncontrolled growth of cancer cells. In the case of stomach (or gastric) cancers, it can be used to treat gastric adenocarcinomas and gastric neuroendocrine tumors (NETs).

When cells grow and divide to form new cells, they go through a series of phases called the cell cycle, which involves copying their genetic material (DNA). Chemotherapy works by interfering with DNA and the cell cycle, preventing the cells from dividing uncontrollably and killing them.

Chemotherapy drugs are unable to differentiate between healthy cells and cancer cells, which means that healthy cells can be affected by these drugs. However, most normal, healthy cells are able to repair the damage caused by chemotherapy and will recover from its effects over time. On the other hand, because cancer cells are mutated (altered), they usually do not recover from the effects of chemotherapy, making it an effective treatment for cancer. Moreover, cancer cells are more vulnerable to chemotherapy drugs because they form new cells at a much faster rate than normal cells. This makes them more susceptible to chemotherapeutic drugs, which interfere with DNA and the cell cycle.

While chemotherapy can be used on its own, it is often given in conjunction with other forms of cancer treatment. For gastric adenocarcinomas, it is often combined with radiation therapy, targeted therapy and immunotherapy. On the other hand, chemotherapy is typically used together with targeted therapy and locoregional treatments (like ablation and embolization) in the treatment of gastric NETs. The aim of this is to make the treatment regimen more effective as a whole. You may also receive one chemotherapy drug at a time or a combination of different drugs at the same time as part of your chemotherapy regimen.

Chemotherapy drugs can be administered orally or as an infusion into your veins (intravenously), after which they travel through the bloodstream to kill cancer cells that have spread throughout the body. This is known as systemic chemotherapy, which is especially useful for cancers that have metastasized. For this reason, systemic chemotherapy is typically used for high-grade gastric NETs.

Chemotherapeutics can also be administered to specific anatomical regions, such as an organ or body cavity, to target cancer cells in that area of the body. This is called regional chemotherapy. An example of regional therapy is hyperthermic intraperitoneal chemotherapy (HIPEC), in which heated chemotherapy drugs are administered directly into the peritoneal cavity (the space containing abdominal organs) via a thin tube immediately after the surgeon removes as much tumor tissue as possible. This is to kill any remaining cancer cells that were not visible during surgery. HIPEC can be used to target advanced gastric cancers that have spread to other organs, which cannot be removed completely with surgery.

Your medical oncologist will administer chemotherapy in cycles, which consist of treatment sessions with periods of rest in between. Each cycle typically lasts for a few weeks. Your chemotherapy regimen will involve a specific number of cycles given over a set period of time. Most chemotherapy regimens last for up to eight cycles over three to six months. However, the frequency of your treatment sessions and the duration of your chemotherapy regimen may vary depending on the type and stage of your cancer.

Chemotherapy can take a toll on your body especially considering the duration of the treatment. It is also important to take care of your mental and emotional health as you undergo this journey. You may find it helpful to seek support from friends and family. They can provide emotional support, assist with daily tasks and offer a listening ear when you need it most.

Chemotherapy can be administered in different settings for different reasons, which include:

• Neoadjuvant chemotherapy: Chemotherapy administered before surgery is known as neoadjuvant chemotherapy. Sometimes, combined with radiation therapy (chemoradiation), the aim of this is to shrink the gastric tumor so that it is easier to remove during the operation.
• Adjuvant chemotherapy: Chemotherapy given after surgery is called adjuvant chemotherapy. It is sometimes combined with radiation therapy (chemoradiation). The goal of adjuvant chemoradiation is to kill any remaining cancer cells that were not visible during the operation and subsequently left behind. This can happen if the cancer has grown deep into the stomach wall or spread to nearby lymph nodes. Adjuvant therapy, therefore, lowers the chances of the cancer coming back (cancer recurrence).
• Perioperative chemotherapy: Chemotherapy before and after surgery is called perioperative chemotherapy. The objectives of this treatment are to shrink the gastric tumor so that surgical removal is easier and to reduce the chance of cancer recurrence.
• Palliative care: Chemotherapy may be recommended for advanced gastric cancers, where the cancer has spread to distant parts of the body and cannot be removed with surgery. In this case, the aim of this treatment is to control cancer growth, alleviate symptoms and maintain your quality of life. This is known as palliative care.

Your doctors will take into account several factors when deciding whether you should receive chemotherapy as part of your treatment plan. These include the type of gastric cancer you have, the cancer’s stage and other factors, like your overall health. In general, people with gastric adenocarcinomas and gastric NETs receive chemotherapy in the following circumstances:

Gastric adenocarcinomas

Chemotherapeutics are generally used across all four stages of gastric adenocarcinomas but in different situations. If you’ve been diagnosed with a stage I, II, or III gastric adenocarcinoma that can be surgically removed (resectable), you may receive neoadjuvant and/or adjuvant chemotherapy.

If your tumor cannot be removed with surgery (unresectable), your doctors may recommend a first round of treatment with chemotherapy and/or radiation. After reassessing the extent of your cancer, if results show that the tumor still cannot be removed safely, the focus of your treatment may shift to palliative care using chemotherapeutics. Stage IV gastric adenocarcinomas are treated in a similar way, which means you may receive chemotherapy as part of your palliative care plan.

Gastric NETs

Low-grade NETs originating from the gastrointestinal tract usually do not respond well to chemotherapeutic agents. For this reason, to slow tumor growth, chemotherapy is generally used only for high-grade carcinoid tumors or neuroendocrine carcinomas (NECs) that:

• are unresectable,
• have spread to other regions of the body and/or
• have not responded to other drugs such as octreotide.

Some gastric NETs are capable of releasing hormones that cause symptoms such as flushing and abdominal pain. This collection of symptoms is called carcinoid syndrome, which is more common among people with metastatic NETs. Chemotherapy can be used to ease the severe symptoms of carcinoid syndrome.

Chemotherapeutics used in the treatment of gastric cancers work by damaging DNA and disrupting the cell cycle in various ways. These types of drugs include:

Alkylating agents

Alkylating agents are a class of drugs that prevent cancer cells from dividing by damaging DNA directly. These drugs work in all cell cycle phases and are commonly used to treat numerous types of cancer. Examples of alkylating agents used for gastric adenocarcinomas include cisplatin, carboplatin and oxaliplatin. On top of those drugs, streptozocin, dacarbazine and temozolomide are also used to treat gastric NETs.

Antimetabolites

Antimetabolites are drugs that interfere with DNA and RNA by acting as substitutes for the normal building blocks of these two biomolecules. As a result, cancer cells can no longer create copies of their genetic material and are thus unable to divide and form new cells. Examples of antimetabolites used for gastric cancers include 5-fluorouracil (5-FU), capecitabine and the trifluridine/tipiracil combination pill.

Antitumor antibiotics

Antitumor antibiotics work in two ways. First, they disrupt the creation of proteins, which are necessary for cell survival, by preventing ribonucleic acid (RNA) synthesis. Second, they can break up DNA strands and slow or stop the process of synthesizing DNA, which cells need to grow and survive.

Anthracyclines are a type of antitumor antibiotic that interferes with enzymes responsible for copying DNA during the cell cycle. Enzymes are proteins that start or accelerate chemical reactions in cells.

Epirubicin and doxorubicin are anthracyclines used in treating gastric adenocarcinomas and gastric NETs, respectively.

Mitotic inhibitors

Also known as plant alkaloids, these drugs are derived from natural products like plants. They inhibit the cell’s ability to divide and form new cells, a process called mitosis. They can also damage cells in all phases of the cell cycle by interfering with enzymes that make proteins needed for cell replication. Docetaxel and paclitaxel are two mitotic inhibitors that are commonly used to treat gastric adenocarcinomas.

Topoisomerase inhibitors

These drugs interfere with topoisomerases, which are enzymes that separate DNA strands so that DNA can copy itself during the cell cycle. Disrupting the function of these enzymes prevents the cancer cells from dividing and also damages their DNA. Topoisomerase inhibitors can be further divided into two groups depending on which enzyme they affect: topoisomerase I or II. Two topoisomerase inhibitors that are used for gastric cancers are irinotecan and etoposide.

While chemotherapy drugs can be used on their own, more often than not, you will receive a combination of drugs as part of your chemotherapy regimen. While different drug combinations are used in the treatment of gastric adenocarcinomas and gastric NETs, common combinations across these two types of gastric cancers include:

• FOLFIRI: leucovorin, 5-FU and irinotecan
• FOLFOX: leucovorin, 5-FU and oxaliplatin
• XELOX: capecitabine and oxaliplatin

Your doctors will decide which drug combination is best for you depending on factors such as the stage of your cancer, whether chemotherapy is combined with radiation therapy and other health considerations. You may experience more side effects from three- or four-drug combinations, which are typically reserved for patients in very good health who can be closely monitored by their doctors.

The field of cancer research continues to look into new chemotherapy drug combinations that could potentially be used to treat different types and stages of gastric cancer. This could lead to more efficient treatment methods and improved outcomes for the future of gastric cancer patients. If you have any questions regarding chemotherapy and its drug combinations, consult your doctors and cancer care team.