Antineoplastic agents are medications used to treat cancer. Except for the usual antineoplastics, there are other medications that can be also used to treat various forms of cancer, particularly acute lymphoblastic leukemia or ALL, ovarian cancer, and cutaneous T-cell lymphoma.
Other antineoplastics that are commonly used include asparaginase, and pegaspargase, which are given intramuscularly or intravenously to treat acute lymphoblastic leukemia, as well as altretamine, which is taken orally to treat ovarian cancer. Then there’s azacitidine, a medication that can be administered orally, intravenously or subcutaneously to treat myelodysplastic syndrome or acute myeloid leukemia; hydroxyurea, which is administered orally in clients with chronic myeloid leukemia or head and neck cancer; and irinotecan, which is administered intravenously to clients with metastatic colorectal cancer.
Once administered, what asparaginase and Pegaspargase do is break down asparagine, which is a non-essential amino acid, into aspartic acid and ammonia. Cancer cells can’t synthesize asparagine themselves, so this impairs their protein synthesis, ultimately stopping cellular processes and causing apoptosis.
On the other hand, the way altretamine works is not perfectly clear, but it could damage cancer cells by crosslinking of DNA, which means the agent links two DNA bases together, forming cross-bridges. Cross-linking prevents DNA from being separated for essential cell processes, like replication or transcription, eventually resulting in cancer cell death and stopping the multiplication of cancer cells.
Next, azacitidine causes damage to double stranded DNA during cell replication, while hydroxyurea and irinotecan inhibit enzymes involved in DNA synthesis, ultimately stopping cancer cell division. Irinotecan in particular belongs to a group of medications called topoisomerase I inhibitors, so it inhibits this enzyme to eventually cause double stranded DNA breaks and halt cell replication.
Unfortunately, these medications can also damage healthy cells and cause side effects. All of them, with the exception of asparaginase and Pegaspargase can cause dermatological reactions, like skin rashes, eczema, pruritus and alopecia; and bone marrow toxicity, which is a boxed warning for altretamine, hydroxyurea and irinotecan. Bone marrow suppression can lead to anemia; leukopenia, increasing the risk of infections; and thrombocytopenia, increasing the risk of bleeding.
Gastrointestinal toxicity, which can manifest as nausea, vomiting or diarrhea, is also a common side effect, and irinotecan actually has a boxed warning for causing severe diarrhea. Other boxed warnings include neurotoxicity for altretamine, and the risk of developing a secondary malignancy after prolonged use for hydroxyurea.
And now for specifics. Azacitidine can cause injection site reactions, as well as fever, fatigue, respiratory infections, nephrotoxicity and tumor lysis syndrome. Asparaginase and Pegaspargase can both cause serious hypersensitivity reactions, and asparaginase can additionally cause fever, hepatotoxicity, nephrotoxicity, and hyperglycemia. Altretamine can also cause hepato- and nephrotoxicity, while hydroxyurea also comes with a risk of fever, headache and stomatitis.
Finally, treatment with irinotecan can lead to cholinergic syndrome, which encompasses a lot of parasympathetic reactions, including diaphoresis; or excessive sweating; flushing; increased peristalsis; miosis; sialorrhea, or excessive salivation; and rhinitis. Other side effects for irinotecan include fever, neurotoxicity, hepatotoxicity, and pulmonary toxicity.
Now, these other antineoplastics are generally contraindicated during breastfeeding, and they should also be used with caution during pregnancy. Asparaginase andPegaspargase should also be avoided in clients with a history of pancreatitis, thrombosis or hemorrhagic events with previous asparaginase treatment. Altretamine should be used with caution alongside monoamine oxidase inhibitors treatment, since using the two together can increase the risk of hypotension.
Hydroxyurea, on the other hand, should be used with caution in the elderly population, people with renal problems, or those who have received radiation therapy in the past; and when used together with some medications used to manage the HIV infection, that can increase the risk of hepatotoxicity, peripheral neuropathy and pancreatitis. Finally, irinotecan should be given with caution in the elderly population, people with renal disease, or people with hepatic impairment.
