McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 4  Antineoplastic agents

The evidence

BOX 14.2

drugs. These agents also jeopardise the immune system by causing bone marrow suppression , inhibiting the blood-forming components of the bone marrow and interfering with the body’s normal protective actions against abnormal cells. The person’s haematological profile must always be assessed for toxic effects. People also need to understand the importance of returning every few weeks to go through the chemotherapy, with its adverse effects, over and over again. Many antineoplastic drugs often result in another adverse effect: cancer itself. Cell death due to these agents increases the need for cellular growth, placing the person at increased risk for mutant cell development. Most cancer sufferers are not considered to be “cured” until they have been cancer-free for a period of 5 years due to the possibility that cancer cells will emerge from dormancy to cause new tumours or problems. No cells have yet been identified that can remain dormant for longer than 5 years, so the chance of the emergence of one after that time is very slim. A cancerous mass may be so large that no therapy can arrest its growth without killing the host. In such cases, antineoplastic agents are used as palliative therapy to shrink the size of the tumour and alleviate some of the signs and symptoms of the cancer, decreasing pain and increasing function. Here the goal of drug therapy is not to cure the disease but to try to improve the person’s quality of life in a situation in which there is no cure. Some emerging antineoplastic agents are discussed in Box 14.2. ALKYLATING AGENTS Because alkylating agents can affect cells even in the resting phase, these drugs are said to be non–cell cycle-specific (see Figure 14.4). They are most useful in the treatment of slow growing cancers, which have many cells in the resting phase. Alkylating agents (see Table 14.1) include the following drugs: busulfan New drugs for the battle against cancer Arsenic trioxide (Phenasen), known as a poison in forensic medicine, has been approved for the induction and remission of promyelocytic leukemia (PML) in people whose disease is refractory to conventional therapy and whose leukemia is characterised by t(15;17) translocation of PML/RAR-alpha gene expression. It is given intravenously at a rate of 0.15 mg/kg per day until bone marrow remission occurs and then 0.15 mg/kg per day starting 3 to 6 weeks after induction.The person needs to be screened carefully for toxic reactions. Other drugs are under development that target specific areas of the human genome. In the future, antineoplastic

( Busulfex , Myleran ), carboplatin ( Carbaccord ), car­ mustine ( BiCNU , Gliadel ), chlorambucil ( Leukeran ), cisplatin (generic), cyclophosphamide ( Cytoxan, Endoxan) , dacarbazine (generic), fotemustine ( Muphoran ), ifosfamide ( Holoxan ), lomustine ( CeeNU ), melphalan ( Alkeran ), oxaliplatin ( Oxalatin, Xalox ), procarbazine ( Natulan ), temozolomide ( Astromide, Temizole, Temodal ) and thiotepa (generic). Therapeutic actions and indications Alkylating agents produce their cytotoxic effects by reacting chemically with portions of the RNA, DNA or other cellular proteins, being most potent when they bind with cellular DNA. The oldest drugs in this class are the nitrogen mustards, and modifications of the structure of these drugs have led to the development of the nitrosoureas. These drugs are most useful in the treatment of slow growing cancers such as various lymphomas, leu­ kaemias, myelomas, some ovarian, testicular and breast cancers, and some pancreatic cancers. See Table 14.1 for usual indications for each of the alkylating agents. These agents are not used interchangeably. Pharmacokinetics The alkylating agents vary in their degree of absorption, and little is known about their distribution in the tissues. They are metabolised and sometimes activated in the liver, with many of these agents using the cytochrome P450 systems. They are excreted in the urine. Contraindications and cautions Alkylating agents are contraindicated during pregnancy and breastfeeding due to their potential for severe effects on the fetus and neonate. Caution is necessary when giving alkylating agents to any individual with a known allergy to any of them; with bone marrow suppression, which is often the index for redosing and dosing levels ; Several familiar drugs are being studied for their ability to block angiogenesis. By blocking the development of new blood vessels to feed the tumour, the growing cells in the tumour will lack nutrition and oxygen and will not be able to survive. Celecoxib (Celebrex), an anti-inflammatory drug, is being studied in various cancer combination-drug trials for this effect. Some low-molecular-weight heparins, such as dalteparin (Fragmin), are also being studied for this effect. drugs may be able to target abnormal cells and not affect the healthy cells.This could relieve the suffering of many people undergoing cancer chemotherapy.