Chemotherapy: Antimetabolites (methotrexate, pemetrexed, gemcitabine)

Antimetabolites are chemotherapy drugs that are used to kill cancer (malignant) cells. Antimetabolites are drugs that may be similar in structure to substances that are essential for growth and division of both normal and cancerous cells or may combine with enzymes to interfere with normal metabolic processes within cells. These drugs are most effective in blocking growth and division of rapidly growing tumors. As a chemotherapy drug, antimetabolites are a systemic treatment, able to travel throughout the body to kill cancer cells anywhere in the body.1,2 Antimetabolites used for lung cancer include pemetrexed (Alimta®), gemcitabine (Gemzar®), and rarely, methotrexate (Otrexup®, Rasuvo®, or Trexall®).

Pemetrexed (Alimta®)

Pemetrexed is an antimetabolite that is used to treat some lung cancers, including certain forms of malignant mesothelioma and non-squamous, non-small cell lung cancer (NSCLC). Depending on the individual patient’s situation, pemetrexed may be used alone or in combination with certain other treatments.3. Pemetrexed is given to the patient through an IV line, and patients usually are given folic acid and vitamin B12 supplements to reduce side effects from treatment. The dosage of pemetrexed is determined by many factors, including the type of cancer, the patient’s general health, and the patient’s height and weight.2

Pemetrexed may cause side effects. Common side effects (experienced by greater than approximately 30 percent of patients receiving pemetrexed) include fatigue, and nausea. Less common side effects occurring in approximately 10-29 percent of patients include low platelets (increasing the risk of bleeding), low white blood cells (increasing the risk of infection), low red blood cells (anemia), vomiting, diarrhea, sore throat, mouth sores, poor appetite, or a rash. For most people, side effects from pemetrexed are reversible and tend to go away after treatment is finished.2 This is not a complete list of side effects. Tell your healthcare provider about all conditions, medications, and health history before beginning treatment with pemetrexed.

Gemcitabine (Gemzar®)

Gemcitabine is a chemotherapy drug that is classified as an antimetabolite. It is used to treat multiple cancers, including non-small cell lung cancer (NSCLC), pancreatic cancer, bladder cancer, soft-tissue sarcoma, metastatic breast cancer, and ovarian cancer. Gemcitabine is given to the patient through an IV line, and the dosage and schedule of gemcitabine is determined by many factors, including the type of cancer, the patient’s general health, and the patient’s height and weight.2

Gemcitabine may cause side effects. Common side effects (experienced by greater than approximately 30 percent of patients receiving gemcitabine) include flu-like symptoms, fever, fatigue, mild nausea, vomiting, poor appetite, skin rash, low white blood cells (increasing the risk of infection), low red blood cells (anemia), low platelets (increasing the risk of bleeding), temporary increases in liver enzymes, and blood or protein in the urine. Less common side effects occurring in approximately 10-29 percent of patients include diarrhea, weakness, hair loss, mouth sores, difficulty sleeping, and shortness of breath. For most people, side effects from gemcitabine are reversible and tend to go away after treatment is finished.2 This is not a complete list of side effects. Tell your healthcare provider about all conditions, medications, and health history before beginning treatment with gemcitabine.

Methotrexate (Otrexup®, Rasuvo®, or Trexall®)

Methotrexate is an anticancer chemotherapy drug that is classified as an antimetabolite. It is rarely used to treat lung cancer,  but may be used in several other cancers, such as acute lymphoblastic leukemia, osteosarcoma, non-Hodgkin lymphoma, breast cancer, advanced head and neck cancers, and stomach cancer. Depending on which disease it is being used in, methotrexate can be given to the patient through an IV (intravenous) line, as an injection into a muscle (intramuscular), as an intrathecal injection (directly into the spinal fluid), or as a pill form to be taken by mouth. The dosage and schedule of methotrexate is determined by several factors, such as the patient’s height and weight, general health, and type of cancer.2

Methotrexate may cause side effects. Common side effects (experienced by greater than approximately 30 percent of patients receiving methotrexate) include low white blood cells (increasing the risk of infection), low red blood cells (anemia), low platelets (increasing the risk of bleeding), mouth sores, and poor appetite. Less common side effects occurring in approximately 10-29 percent of patients include kidney toxicity, skin rash, diarrhea, nausea, vomiting, increases in liver enzymes on blood tests, darkening of the skin where previous radiation therapy has been given, hair loss, skin photosensitivity (sensitivity to sun light), or loss of fertility. For most people, side effects from methotrexate are reversible and tend to go away after treatment is finished.2 This is not a complete list of side effects. Tell your healthcare provider about all conditions, medications, and health history before beginning treatment with methotrexate.

Managing side effects

There are many options available to help manage side effects from chemotherapy, and patients should talk to their health care professional about all side effects they experience. Hydration (fluid intake) is very important while receiving chemotherapy, and patients are generally encouraged to drink an adequate amount of fluids every day, which may vary patient to patient (patients should check with their doctor if they have a fluid restriction). To lower the risk of infection, patients receiving chemotherapy may be advised to avoid crowds, people with colds, and wash their hands often.2

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Written by: Emily Downward | Last reviewed: May 2021.