Chemotherapy in Metastatic Colorectal Cancer - An Overview

Introduction:

Colorectal cancers are the third most common type of carcinoma. These types of cancer involve the digestive tract's last part, the large intestine, and the rectum. Early stages of colorectal cancer can be seen as non-cancerous polyps. Treatment of colorectal cancers includes both surgical therapy and chemotherapy. It depends on the stage at which the cancer has progressed. In metastatic cancers, it is difficult to remove all the tumors surgically due to their spread to different parts of the body. So chemotherapy is considered in metastatic tumors.

What Is Colorectal Cancer?

Colorectal cancer involves the growth of polyps in the colon (part of the large intestine) and rectum. Colorectal cancer develops in the mucosal lining of the colon. Colorectal cancer can appear either at nearby sites or can be seen at a distant site which is called metastasis. In severe cases, before the diagnosis of colorectal cancer, it can be metastasized to different parts of the body, called metastatic colorectal cancer.

What Are the Symptoms of Colorectal Cancer?

The signs and symptoms of colorectal cancer include diarrhea or constipation, blood in stool, abdominal discomfort, pain, fatigue, bloated stomach, and weight loss. During the early stage of colorectal cancer, these symptoms can be observed. The cause of colorectal cancer is not clear. When there is a change in DNA (deoxyribonucleic acid), the cells multiply, resulting in tumor growth.

What Are the Diagnostic Aids to Confirm Colorectal Cancer?

The diagnostic methods to find out colorectal cancer include-

• Complete Blood Count: A complete blood count test is performed to screen all the parameters of the blood, like the red blood cells, white blood cells, etc.

• Carcinoembryonic Antigen Assay: Carcinoembryonic antigen assay measures the level of carcinoembryonic antigen or CEA in blood, which is an indicator of cancer.

• Computed Tomography: CT (computed tomography) scan uses X-rays and computer technology to get image slices of the colon.

• Magnetic Resonance Imaging: MRI (magnetic resonance imaging) uses high magnetic fields to create an image of the colon and rectum.

• Positron Emission Tomography: PET (positron emission tomography) scan uses radioactive substances to create an image of abnormal growth.

• A Biopsy: Tissue containing cancerous cells is taken and visualized under a microscope.

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What Are the Treatment Options for Metastatic Colorectal Cancer?

The treatment options for metastatic colorectal cancers are surgical therapy, chemotherapy, and immunotherapy.

• Surgical Therapy- People with colorectal cancer metastasized to the liver can be surgically resected and cured in 30 percent of the cases. Surgical resection is not considered if cancer has metastasized outside the liver. Surgical treatment is also considered if cancer has metastasized to the lungs, but it is only to a limited extent. The surgical methods include laparoscopic surgery (an instrument passed through the gastrointestinal tract to remove the cancerous cells), colostomy for rectal cancer, and radiofrequency ablation (freezing the tumor, also called cryoablation).

• Chemotherapy- In most metastatic colorectal cancer, surgery is impossible as cancer has been spread to different body parts. Then the treatment option for such cases is chemotherapy. People on the borderline case for surgery are advised to undergo chemotherapy before the surgery to reduce the symptoms and tumor growth. Chemotherapy is also recommended in people who underwent surgical removal of cancer metastasizing to the liver.

• Immunotherapy- Immunotherapy uses the body’s immune system to fight against the cancer cell that helps in tumor growth. Nivolumab, Pembrolizumab, and Ipilimumab are the common immunotherapy agents used to fight against cancer cells.

• Radiation Therapy- High radiation beam is used to kill cancer cells. Two methods exist to do radiation therapy, either from an external or an internal source like pills or seeds inserted into the body to direct radiation to the cancerous cells.

What Type of Chemotherapy Is Used in Metastatic Colorectal Cancer?

In most cases, chemotherapy is administered intravenously. Sometimes, when the drug is given directly to the liver, it is called hepatic intra-arterial chemotherapy.

1. Conventional Chemotherapeutic Drugs- These chemotherapeutic drugs inhibit the growth of rapidly growing cancerous cells. This can also inhibit the growth of normal cells like bone marrow and hair cells, causing hair loss which is a disadvantage of these drugs.

• Fluorouracil with a combination of Leucovorin intravenously.

• Capecitabine orally.

• Oxaliplatin intravenously.

• Irinotecan intravenously.

• Trifluridine along with Tipiracil orally.

2. Targeted Chemotherapeutic Drugs- These are targeted at specific cells, and the drugs do not directly interfere with normal cells. The side effects of this therapy are lesser than the conventional chemotherapy.

• Bevacizumab is usually given with Capecitabine, Oxaliplatin, or Irinotecan.

• Ramucirumab.

• Aflibercept.

• Regorafenib.

• Cetuximab and Panitumumab.

• Larotrectinib.

What Is the First Line of Chemotherapeutic Treatment for Metastatic Colorectal Cancer?

The first line of chemotherapy treatment is a combination of drugs as mentioned below:

• Oxaliplatin, Fluorouracil, and Leucovorin.

• Irinotecan, Fluorouracil and Leucovorin.

• Oxaliplatin, Fluorouracil, Irinotecan and Leucovorin.

• Oxaliplatin and Capecitabine.

Patients with poor tolerance to first-line treatment due to other medical conditions can use Fluorouracil and Leucovorin intravenously with or without Bevacizumab for a short-term infusion or Capecitabine with or without Bevacizumab daily two times for 14 days.

What Are the Side Effects of Chemotherapy in Colorectal Cancer?

The side effect of chemotherapy depends on the drug type, duration, and combination. Some of the side effects of the drugs are listed below.

• Fluorouracil and Leucovorin result in diarrhea and inflammation in the mouth and guts.

• Capecitabine can result in hand-foot syndrome.

• Irinotecan results in diarrhea, fatigue, anemia (less blood count), and alopecia (hair fall).

• Oxaliplatin can cause numbness in the hands and feet and spasms when consuming cold food or drinks.

• Bevacizumab, Ramucirumab, and Aflibercept can result in decreased wound healing, gastrointestinal bleeding, increased blood pressure, and blood clotting, resulting in strokes and heart attacks.

• Regorafenib can cause gastrointestinal bleeding, increased blood pressure, diarrhea, hand-foot syndrome, and liver damage.

• Cetuximab can cause skin rashes, low levels of magnesium in the blood, blood clots, and diarrhea.

• Panitumumab results in skin rash, blood clots, and low levels of magnesium in the blood.

• Encorafenib causes weakness in the heart muscle and visual blurring.

• Nivolumab, Pembrolizumab, and Ipilimumab cause inflammation in the lungs, skin, kidneys, and liver.

• Larotrectinib and Entrectinib result in neurological changes like changes in mental status, difficulty walking, and abnormal liver counts.

Conclusion:

Colorectal cancers can reappear despite early diagnosis and treatment. Therefore frequent follow-up with the doctor is necessary to check for recurrence. People with metastatic colorectal cancers cannot be completely cured with surgery. To reduce the symptoms and prolong life, chemotherapy is the treatment option. In some cases, chemotherapy and surgery are performed depending on the severity of the cancer.

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