Treatment Options - Surgery, Chemotherapy, Targeted Treatments, and Radiation

The treatment for stomach cancer depends on its stage--the size and location of the tumor, whether the cancer has spread, and the patient's overall health. Treatments may include surgery, chemotherapy (possibly before and after surgery), targeted treatments, and radiation or any combination of these treatments.

Surgery

When the cancer is confined to the stomach, surgery is the essential component to all curative treatments for gastric cancer. The goal of surgery for potentially curable stomach cancer is to remove all of the cancer while preserving as much of the patient's normal gastric function as possible. All stomach cancer surgery is complex and ideally should be performed by an experienced surgical oncologist working together with other members of a multidisciplinary team to achieve optimal outcomes.

The surgery usually consists of removing the affected portion of the stomach with adequate margins and the nearby lymph nodes, a procedure known as gastrectomy.  This can be either a partial or total removal of the stomach.  The specific operation performed is based on the location and pathologic type of stomach cancer.  There are a variety of options for reconnecting the intestinal tract to the stomach or esophagus to re-establish intestinal continuity and permit the ability to eat regular food. The reconstructive options depend on the type and extent of the operation needed to remove the tumor. For example, a total gastrectomy might be required for a more diffuse type of gastric cancer in order to ensure that the entire tumor has been removed.  In these situations, the small intestine is connected directly to the esophagus with or without some type of reservoir or pouch reconstruction.  In other situations, a portion of the native stomach can be preserved and the small intestine is connected directly to the residual stomach. Occasionally, a temporary feeding tube is inserted through the skin into the small intestine at the time of surgery to provide additional nutrition during the recovery period. Most patients spend about a week in the hospital and then recover at home for about 4-8 weeks before resuming regular activities or additional treatments.

Although surgery is an essential part of any curative approach to stomach cancer, surgery alone is often not enough.  Most patients with potentially curable gastric cancer will receive additional therapy to prevent the cancer from recurring or coming back.  These additional (also called adjuvant therapy) treatments for gastric cancer are sometimes given before or after surgery depending on the type and stage of gastric cancer involved. The rationale for combining these treatments with surgery is to treat any residual microscopic cancer cells that may exist before or after surgery.  In some situations, chemotherapy is given for a few months before surgery followed by a recovery period prior to the planned surgery.  Additional chemotherapy may follow.  In other situations, a combination of chemotherapy and radiation therapy may be given after the patient has adequately recovered (generally 4-8 weeks) from the operation. The amount and type of treatment depends on the extent of the cancer and the overall health of the patient.

For patients with metastatic gastric cancer that cannot be cured with an operation, surgery may still be recommended based on symptoms such as obstruction, bleeding or pain that cannot be controlled by other means.  These operations are done for palliative relief of symptoms and require experience, judgment, and realistic expectations of the palliative goals of treatment.

Removing a portion or all of the stomach has an impact on eating and nutrition but perhaps less so than most people would imagine.  Most patients initially experience a diminished appetite and a sensation of being full with relatively little food intake.  As a consequence, patients often start off eating smaller meals spread out over more time and have to "work" more at getting enough nutrition to maintain weight.  There may be some changes in the recommended diet depending on the type of surgery performed; however, many patients are able to gradually resume eating regular food with some modifications.  It frequently takes several months to settle into a new eating routine.  The human body and intestinal tract have an amazing capacity to adapt and compensate for the changes brought about by surgery and the other treatments employed for gastric cancer.

By Martin McCarter, MD
Professor of Surgery and Surgical Director of the Esophageal and Gastric Multidisciplinary Cancer Clinic
University of Colorado School of Medicine
Aurora, Colorado

(January 1, 2014)

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Chemotherapy

Patients with advanced or metastatic gastric cancer can benefit from chemotherapy in managing both their disease and its symptoms. A number of studies have shown that patients undergoing chemotherapy had a higher quality of life than those receiving best supportive care. There are currently a number of drugs, combinations of drugs, and targeted therapies that have been shown to be effective in extending the lives of patients with advanced gastric cancer. There are also multiple clinical trials underway designed to test new agents and improve the uses of established ones. Choosing the right chemotherapy regimen depends on a number of factors including the location and extent of the disease, its molecular profile, previous treatment, potential side effects or toxicity, and the overall health of the patient. Many patients with advanced gastric cancer suffer from significant physical symptoms related to their cancer and may not be candidates for some types of chemotherapy.

One of the major limiting factors in cancer treatment is a phenomenon known as drug resistance. This occurs when a drug or drugs that have been effective in controlling a cancer stop working. The reasons for this are very complex and are being studied by researchers around the world. For gastric cancer, there are second and third line chemotherapy regimens that can be used once the first line therapy fails.

Patients should be seen in cancer centers that can provide multidisciplinary approaches, see a high volume of gastric cancer patients and have the ability to address the multiple symptoms and side effects that are consequences of both the cancer and its treatment. Patients should also be aware of the possibility of enrolling in clinical trials and discuss these options with their treatment team. As with all treatment options for gastric cancer, especially in its advanced stages, the decisions regarding appropriate therapy are complicated.

For a list of the cancer drugs approved by the Food and Drug Administration (FDA) for stomach (gastric) cancer, go to

» http://www.cancer.gov/cancertopics/druginfo/stomachcancer

Targeted Treatments

Targeted therapy is a type of treatment that targets a cancer's specific genes, proteins, or the tissue environment that contributes to cancer growth and survival.  Targeted therapy includes drugs that are aimed at specific genes or proteins that are only found in cancer cells or the tissue environment that contributes to cancer growth and survival. It is often used along with chemotherapy and other cancer treatments to block the growth and spread of cancer cells.  Not all tumors have the same targets, so doctors may run tests to match a cancer with the most effective treatment.  A few targeted therapies are approved by the U.S. Food and Drug Administration (FDA) being used to treat stomach (gastric) cancer.  In addition, there are clinical trials which are looking for additional targets and new drugs for those targets.  Targeted therapies are a promising way to personalize stomach cancer treatment but note that resistance to treatment can develop and side effects can be an issue.

The "targets" of targeted therapy

To understand targeted therapy, it helps to understand how cancer cells develop. Cells are the building blocks of every tissue in the body. There are many different types of cells, such as blood cells, brain cells, and skin cells, which each have specific functions. Cancer begins when specific genes in healthy cells mutate or change. Genes tell cells how to produce proteins, many of which help a cell function normally. However, if the genes are mutated, the proteins will be changed as well, resulting in abnormal cell division or delayed cell death.  This causes the cells to grow uncontrollably, forming a mass called a tumor.

By studying cancer cells and how they react to their environment, researchers are finding that specific gene mutations contribute to the development of specific cancers. With this knowledge, they are developing drugs that:

  • Block or turn off signals that tell cancer cells to grow and divide
  • Turn on or promote processes that result in natural cell death
  • Deliver toxic substances specifically to cancer cells to destroy them


Types of Targeted Therapy:

There are three main types of targeted therapy: 

1.    Monoclonal antibodies- These substances, which are made in the laboratory, block a specific target on the outside of cancer cells or in the tissue surrounding the cancer. Think of this as placing a protective plastic plug into an electrical socket to prevent electricity from flowing. Monoclonal antibodies can also deliver toxic substances, such as chemotherapy and radioactive substances, directly to cancer cells. These drugs are usually given intravenously (by IV) because they are large compounds that are not absorbed well by the body.

2.    Oral small drugs- These drugs are usually given in the form of a pill that a patient takes by mouth. The body can absorb these better because they contain smaller chemical components than monoclonal antibodies (see above). These oral drugs usually block processes inside cancer cells that stimulate them to multiply and spread.

3.    Angiogenesis Inhibitors- There is also a class of targeted therapy drugs called angiogenesis inhibitors that target the tissue that surrounds a tumor. These drugs focus on stopping angiogenesis, which is the process of making new blood vessels. Because a tumor needs the nutrients delivered by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to essentially "starve" the tumor by blocking the development of these new blood vessels.

Matching a patient to treatment

Recent studies show that not all tumors have the same targets, which explains why a targeted treatment does not work for every person.  Researchers have learned that about 20% to 25% of all stomach cancers have too much of a protein called human epidermal growth factor receptor 2 (HER2), which fuels tumor cell growth.  Gastric cancer patients should have their tumor tested for HER2 so doctors can provide the most effective treatment and not expose patients to unnecessary side effects and costs with drugs that are not likely to be helpful.  If the results show that the cancer is HER2 positive, there are several FDA-approved drugs that may be recommended as treatment options including Trastuzumab (Herceptin) and there are several clinical trials being conducted as well.

To find the most effective treatment, your doctor should order tests to identify the genes, proteins, and other factors unique to your tumor. Because many of these treatments have some degree of side effects and the treatments can be expensive, doctors are making efforts to match each patient's tumor to the most effective treatment whenever possible.

There are a number of targeted therapies that have been approved to treat different types of cancer but remember that a targeted treatment will not work if the tumor does not contain the target.  However, remember that the presence of the target also does not guarantee that the treatment will work. Talk with your doctor or another member of your health care team for more information about your treatment options.

Challenges of targeted therapies

Although the idea of targeting a drug to a tumor seems straightforward, this approach is complicated and not always effective. For example, the target in the cancer cell may turn out not to be as important as first thought, and the drug will not provide much benefit to patients. Or, the cancer may become resistant to the treatment, meaning it no longer works, even if it did at first. Finally, these drugs may cause serious side effects, although the side effects are usually different than those seen with traditional chemotherapy. For example, patients receiving a targeted therapy may develop skin, hair, nail, eye, and/or heart problems and others.

Although the development of targeted treatments is a breakthrough in cancer treatment, only a few cancers can be eliminated with these drugs alone.  With a few exceptions, patients with cancer usually receive a combination of targeted therapy and surgery, chemotherapy, radiation therapy, and/or hormonal therapy.  As doctors gain more knowledge about specific changes in cancer cells, more targeted treatments will be developed.

Radiation

Radiation therapy uses high-energy X-rays or sub-atomic particles to kill cancer cells in a specific area of the body.

External beam radiation therapy is the type of radiation therapy most often used to treat stomach cancer. This treatment focuses radiation on the cancer from a machine outside the body. Having this type of radiation therapy is like having an x-ray, except that each treatment lasts longer, and the patient usually receives 5 treatments per week over a period of 4-7 weeks.

Before or after surgery, radiation therapy can be used to kill small remnants of the cancer that cannot be seen and removed during surgery. Radiation therapy — especially when combined with chemotherapy drugs such as 5-FU — may delay or prevent cancer recurrence after surgery and may help patients live longer. Radiation therapy can also be used to ease certain symptoms of advanced stomach cancer such as pain, bleeding, and eating problems.

Side effects from radiation therapy for stomach cancer can include:

• Mild skin irritation at the site through which the radiation was delivered

• Nausea and vomiting

• Diarrhea

• Fatigue

• Low blood cell counts

These side effects usually go away within several weeks after the treatment is finished. When radiation is given with chemotherapy, side effects are often worse. Please be sure to tell your doctor about any side effects you have because there are often ways to relieve them. It is also very important that you get treated at a center that has extensive experience in treating stomach cancer.

As approved by:
Joel E. Tepper, MD
Hector MacLean Distinguished Prof of Cancer Research, Dept of Radiation Oncology
UNC/Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina

(February 7, 2014)

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