Page 45 Complete Your CE Test Online - Click Here With any of the above risk factors, the following drugs are typically contraindicated: ● ● Ondansetron. ● ● Droperidol. ● ● Oxaliplatin. In treating cancer and N&V related to cancer drugs, there are a number of other medications that may affect QT interval enough to cause TdP or other arrhythmias in the presence of the risk factors for TdP as noted above, these drugs are not categorically contraindicated as of early 2016, but use caution with [78]: Antiemetic drugs: ● ● Granisetron. ● ● Olanzapine. ● ● Promethazine. Cancer treatment drugs: ● ● Arsenic trioxide. ● ● Bortezomib. ● ● Bosutinib. ● ● Ceritinib. ● ● Crizotinib. ● ● Dabrafenib. ● ● Dasatinib. ● ● Degarelix. ● ● Eribulin. ● ● Lapatinib. ● ● Lenvatinib. ● ● Leuprolide. ● ● Nilotinib. ● ● Osimertinib. ● ● Panobinostat. ● ● Pazopanib. ● ● Sorafenib. ● ● Sunitinib. ● ● Tamoxifen. ● ● Toremifene. ● ● Vandetanib. ● ● Vemurafenib. ● ● Vorinostat. It is important to continue to follow up on new drug additions to this list as new research is published. And of course, new drugs come out all the time that may add to this list as well. Nursing consideration: Avoiding drug combinations that interact via the CYP enzyme system can maintain effectiveness of drug treatments and reduce the incidence of drug toxicity events. Inherited genetic mutations can affect response to drug treatment Germline (inherited) mutations can also affect responses to treatment. For example, women who were born with CYP 2D6 mutations do not produce enough of the enzyme that metabolizes certain drugs (e.g. CYP 2D6 substrates) (see β€œDrug interactions” for more detail). Tamoxifen, which is a commonly used breast cancer treatment that greatly reduces recurrence in women with estrogen receptor-positive breast cancer, must be metabolized by the CYP 2D6 enzyme to its active form, endoxifen. Some studies suggest that women with a germline genetic mutation that lowers CYP 2D6 production do not get the same benefit from tamoxifen as women who metabolize the drug normally. There are other anti-estrogens for women who are not expected to respond to tamoxifen; specifically, the aromatase inhibitors such as anastrozole, letrozole, and exemestane can be used for ER- positive breast cancers. However, there is currently no requirement or recommendation from U.S. experts that women be tested to find out if their CYP 2D6 levels are adequate before starting tamoxifen [81]. Women who have higher CYP 2D6 levels due to a different genetic mutation may get higher levels of active drug, and may be more prone to side effects and toxicities. Unfortunately, there are other germline mutations that can cause problems in cancer treatment. People who have a dihydropyrimidine dheydrogenase (DYPD) mutation can have much higher toxicity and even fatalities with the commonly used cancer drug, 5-Fluorouracil. Thiopurine methyltranserase (TPMT) mutations, which affect about one in 300 people, can result in unexpected toxicity with mercaptopurines. People with UDP-glycosyl- transferase 1A1 mutations can have increased toxicity from irinotecan, with dose-limiting diarrhea and leukopenia. Those with methylenetetrahydrofolate reductase mutations (MTHFR) can have much worse toxicity to methotrexate [83]. Again, most of these problems are discovered after chemotherapy begins, if they are discovered at all. Many cancer treatment centers do not test for these genetic mutations even if they have to stop therapy. This is another reason it is so crucial to assess and document responses to cancer treatment. If treatment with the problem drug is allowed to progress in the face of these mutations, it can result in death (see β€œResources for Nurses”). Hematopoietic stem cell transplants Hematopoietic stem cell transplants (HSCT) provide healthy blood- forming stem cells to replace cells that were destroyed by treatment (and sometimes by disease). The blood-forming stem cells that are used in transplants can come from bone marrow, the bloodstream, or umbilical cords. Transplants can be: ● ● Autologous, i.e. the stem cells come from the patient and are eventually infused into the same patient. ● ● Allogeneic, i.e. the stem cells come from someone else. The donor may be a blood relative but can also be an unrelated match, including banked cord blood from newborns. ● ● Syngeneic, i.e. the stem cells come from a patient’s identical twin. To reduce possible side effects and improve the chances that an allogeneic transplant will work, the donor’s blood-forming stem cells must β€œmatch” [196]. This matching involves human leukocyte antigens (HLA) that determine a person’s tissue type. A match works better when all six of the major HLA antigens match. Sometimes a donor with one mismatched antigen (e.g. a five out of six match) is used. When a transplant uses cord blood from newborns, perfect HLA matching is not as important for success. In unrelated adult donors, sometimes professional will try to match even more than the six major antigens, which requires a deeper look at HLA typing than has been done routinely. Research continues in this area because it can be very difficult to find high level HLA matches for HSCTs [39]. In most cases, stem cell transplants do not work directly against the cancer. Instead, they allow the patient to recover after treatment with very high doses of radiation therapy, chemotherapy, or both. However, in multiple myeloma and some types of leukemia, the stem cell transplant may work against cancer directly through an effect called graft-versus-tumor that can occur after allogeneic transplants. Graft- versus-tumor occurs when white blood cells from the donor attack cancer cells that remain in the body after high-dose cancer treatment treatments. This effect improves the success of the treatments [196]. High doses of chemo and radiation work better at killing cancer cells than standard doses, but they also cause the bone marrow to completely stop working. The HSCT rescues the patient from this lethal situation by providing new stem cells to replace the ones killed by the treatment. Most patients stay in the specialized transplant center hospital during at least part of the transplant process, which can take a few months to complete. The process begins with treatment of high doses of chemotherapy, radiation therapy (usually total body irradiation, or TBI), or a combination of the two. This goes on for a week or two.