Page 25 Complete Your CE Test Online - Click Here to find and destroy the cancer cells. Researchers then grow large batches of these T cells in the lab over the course of two to eight weeks. The T cells that were grown in the lab are then introduced into the patient. ● ● Cytokines are proteins that play important roles in the body’s normal immune responses and also in the immune system’s ability to respond to cancer. The two main types of cytokines used to treat cancer are called interferons (e.g. interferon alfa) and interleukins (e.g. IL-2). There are also drugs, similar to cytokines but do not occur naturally, like thalidomide and lenalidomide, that boost the immune system. ● ● Treatment vaccines work against cancer by boosting the immune response to cancer cells. The treatment vaccines are different from the ones that help prevent disease. An example of this is sipuleucel-T, which is used to treat advanced prostate cancer. ● ● BCG, Bacillus Calmette-Guérin, is an immunotherapy that is used to treat bladder cancer. It is a weakened form of the bacteria that causes tuberculosis. When injected directly into the bladder, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer. Immunotherapy may be given via IV, orally, topically (for very early skin cancer, like imiquimod cream), or intravesically and it is typically given on an outpatient basis, every day, week, or month. Some immunotherapies are given in cycles [171]. Immunotherapy is not yet as widely used as surgery, chemotherapy, and radiation therapy. However, immunotherapies have been approved to treat people with many types of cancer, and many others are being studied in clinical trials [171]. Immunotherapy can cause side effects The side effects depend on the type of immunotherapy. Rarely, immunotherapies may also cause severe or even fatal allergic reactions [171]. The most common side effects are skin reactions at the needle site, such as pain, swelling, redness, or itching. They can also cause flu- like symptoms such as [171]: ● ● Fever. ● ● Chills. ● ● Weakness. ● ● Dizziness. ● ● Nausea or vomiting. ● ● Muscle or joint aches. ● ● Fatigue. ● ● Headache. ● ● Trouble breathing. ● ● Low or high blood pressure. Other side effects include: ● ● Swelling. ● ● Weight gain from fluid retention. ● ● Palpitations. ● ● Sinus congestion. ● ● Diarrhea. ● ● Risk of infection. Drug interactions and effects in cancer treatment CYP 450 enzymes: A clinically important system As mentioned in the “Pre-treatment Assessment” section, most health professionals have heard of the CYP 450 drug interaction issue but many are not sure how it works. CYP 450 enzymes are mostly produced in the liver, but the gut produces them too. About ten of these enzymes can affect drugs in a significant way. These enzymes help to metabolize many drugs so that they can be inactivated and excreted [83]. It is important to know that, not only do the enzymes affect certain drugs, but there are some drugs that can affect the production of the enzymes. This means that one drug can indirectly affect another in significant ways. A drug that requires a certain enzyme to be metabolized is called a substrate of that enzyme. For example, alprazolam (Xanax) is a substrate of enzyme CYP 3A4, which is required to metabolize it. The half-life of this drug is usually about 11 hours (but can vary between six and 27 hours) [219]. This is typically fairly constant in each person, all other things being equal. However, if a person is taking an inducer of CYP 3A4, the alprazolam could leave the body very quickly. If the person is taking an inhibitor of CYP 3A4, the alprazolam blood level could climb much higher and last much longer in the body. Grapefruit and starfruit also act as 3A4 inhibitors, which means that patients taking alprazolam can intensify and extend the activity of this benzodiazepine if they drink grapefruit juice. While this may be a problem, it can be a more severe issue if they are taking a 3A4 substrate such as vincristine or imatinib (Gleevec), which might result in more unpredictable and severe toxicities. The most important of these enzymes are [230]: ● ● CYP 1A2. ● ● CYP 2B6. ● ● CYP 2C8. ● ● CYP 2C9. ● ● CYP 2C19. ● ● CYP 2D6. ● ● CYP 2E1. ● ● CYP 3A4,5,7 (these are typically grouped since they are related and on the same gene; sometimes the whole group is often called simply CYP 3A or the CYP 3A family). Each of these enzymes has drugs that require that particular enzyme to be metabolized (they are substrates of that enzyme), and other drugs that inhibit that enzyme. Most of the enzymes can also be induced (i.e. have their production increased) by certain drugs. To make things more confusing, some people have genetic mutations which cause them to produce more or less of these enzymes. Those people do not have to take the inhibitor drug or the inducer drug to get an unexpected response to the substrate. The CYP 3A4,5,7 (usually called just group CYP 3A) affects a number of drugs used in cancer treatment. Some antidepressants, a couple of important nausea medicines, and tamoxifen are in the CYP 2D6 substrate column. Some common nonsteroidal anti-inflammatory drugs are CYP 2C9 substrates, along with warfarin and a couple of anticonvulsant drugs that have a number of off-label uses. There is no problem as long as the person produces the normal amount of the enzyme needed to metabolize the drugs and is not taking a CYP 2C9 enzyme inhibitor or inducer [92]. Anti-cancer drugs, antiemetic drugs, and CYP enzyme interactions Some of the antiemetic drugs affect or are affected by other drugs via the CYP 450 enzyme system. The NCCN warns, for example, that aprepitant is a substrate of CYP 3A and induces CYP 2C9, although the effect is more pronounced with oral drugs than IV ones [204]. On the other hand, an expert pharmacology website from Indiana University does not list these effects as clinically significant [92]. Interestingly, both of these statements can be true, since some substrates have other routes of excretion besides the one enzyme; and in vitro measurements of CYP enzyme induction or inhibition do not always predict major problems in vivo due to magnitude of effect and other variables [203, 204, 205, 206]. The Indiana University pharmacology expert table of clinically significant issues with drugs commonly used in cancer treatment and nausea and vomiting (N&V) management identifies these possible interactions due to CYP 450 enzymes [92]: ● ● N&V drugs that are affected by the CYP enzyme system: ○ ○ Olanzapine is a 1A2 enzyme substrate. ○ ○ Haloperidol is a 3A family enzyme substrate. ○ ○ Alprazolam is a 3A family enzyme substrate. ● ● Cancer treatment drugs that are affected by the CYP enzyme system: ○ ○ Cyclophosphamide is a substrate of 2C19 and 2B6 enzymes. ○ ○ Ifosfamide is a 2B6 enzyme substrate. ○ ○ Paclitaxel is a 2C8 enzyme substrate. ○ ○ Vincristine is a 3A family enzyme substrate. When any of these drugs are given with other medicines that can inhibit or induce these particular enzymes, the drugs can have their excretion delayed or hastened, respectively. It is a good idea to check new drug information regularly.