describes chemotherapy administered after radiation or surgery.
acting to prevent, inhibit, or halt the development of a neoplasm (a tumor).
programmed cell death.
noncancerous; a term applied to a growth that does not spread or return if removed.
Body surface area (BSA)
a measurement of the external area of the body, generally expressed in square meters (m2) and most often calculated from a patient’s height and weight rather than actually measured; thought to be a more accurate indicator of the patient’s actual size than weight alone.
a disease state in which abnormal cells divide without control and are able to invade other tissues.
cancer that begins in the skin or tissues that cover or line internal organs.
describes an agent (cytotoxin) that kills cells.
describes an agent that protects cells against damage from cytotoxins.
causing nausea and vomiting.
cancer that starts in the bone marrow and causes abnormal cells to enter the blood.
cancer that originates in the lymphatic cells of the immune system.
interference with the bone marrow’s functions, especially production of blood cells and platelets.
death of living tissue.
describes chemotherapy administered before radiation therapy or surgery.
cancer that begins in the connective tissue.
a growth or mass of unneeded cells in the body.
After completing this chapter, you should be able to
List the classes of agents used to treat cancer, including their place in therapy, and give examples of each.
Recognize the side effects of different types of chemotherapeutic agents.
Define medical terms used in chemotherapy management.
List the risk factors for chemotherapy-related nausea and vomiting and discuss medications used in its treatment.
Recognize look-alike/sound-alike medications used in treating the oncology patient.
The body consists of cells, which grow, divide, and reproduce according to the influences exerted by natural controls (hormones, enzymes) and external stimuli (chemicals, medications). Body cells are specialized, with functions ranging from the production of hormones (like those in the endocrine system) to attacking outside invaders (like many in the immune system). Normally, old cells that “wear out” or die are replaced and additional cells (like those in the blood and immune system) are produced when the body needs them. Sometimes, however, this natural cycle of cell production, death, and replacement is disrupted. It may be the result of an outside influence (hazardous chemical or drug) or an error in an internal process; often, it occurs when a cell’s genetic material has suffered change or damage, called mutation. The outcome can be the formation of additional unneeded cells, which grow and reproduce (proliferate) in an uncontrolled manner not responsive to the body’s normal regulation (eg, by hormones) and sometimes not even resembling the original tissues that produced them. The extra or abnormal cells can form a mass or clump of cells, called a tumor. Another name for a tumor is neoplasm, from the Greek roots for new (neo) and growth (plasia).
Some tumors are self-contained. They grow in one place, and while they may cause discomfort or illness because they crowd or interfere with other tissues or even produce natural chemicals in excess of what the body needs, they do not spread to other places or invade body organs and can often be removed and do not return. Such tumors are termed benign and are not cancerous. Other tumors, however, are not as well-behaved. They grow uncontrollably, invade and damage body organs and systems, and may even spread (metastasize), traveling through the blood and lymphatic systems and starting new growths called metastases in other parts of the body. These tumors are termed malignant or metastatic and their spread is called metastasis. While malignant tumors can also be removed, they sometimes grow back, either in the same place or in some other area of the body.
Mrs. Sullivan is a 45-year-old female patient who had surgery to remove a tumor from her large intestine.
Cancer is the term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Unlike many other conditions covered in this text (eg, diabetes), cancer is not really a single disease state, but a term that refers to a group of diseases, usually designated by the type of cell or body tissue from or in which it originates. There are more than 100 different types of cancer.1
Mrs. Sullivan’s tumor started in the lining of her colon. What type of neoplasm is this cancer likely to be?
Some cancers are labeled with the name of the organ in which they began, such as prostate cancer, breast cancer, lung cancer, and colorectal cancer. Basal cell cancer is a malignancy of the basal cells of the skin; melanoma originates in the melanocytes of the skin. Lymphoma starts with the cells of the immune system. A more specific designation specifies the type of tissue a cancer represents. Carcinoma is a cancer that begins in the lining around an internal organ. Sarcoma originates in the connective tissue and may have a more descriptive prefix, with osteosarcoma being a bone cancer, myosarcoma a muscle cancer, and liposarcoma a fatty tissue cancer.
Cancers are also sometimes classified based on the type of cell that makes up the malignancy. Neuroendocrine tumors have been diagnosed in several celebrities in recent years. Regardless of where in the body they form, they have this designation because they release hormones in response to nervous system stimulation. A subgroup of these, carcinoid tumors, usually originate in the gastrointestinal (GI) system or lungs but may spread to other body organs.1
While all cancers are made of malignant cells and are often referred to as malignancies, they are not necessarily all tumors. Like leukemia, which starts in the blood-cell-forming tissues, some cancers proliferate in a malignant way without forming a solid tumor mass; in the case of leukemia, the extra cells crowd out normal cells in the bone marrow and may circulate in the bloodstream.2
More than 1.8 million new cases of cancer are diagnosed each year in the United States.1 Not all cancer is fatal, but more than 600,000 Americans die from cancer annually.1 Although people are warned that many things can cause cancer, the National Cancer Institute’s (NCI’s) list of the most common risk factors includes tobacco, sunlight, ionizing radiation, certain chemicals, some infectious agents, certain hormones, alcohol, poor diet, lack of physical activity, and being overweight.1 Family history and growing older are also predisposing factors. As the NCI points out, however, most people with risk factors will never develop cancer, but avoiding the risks wherever possible reduces the chance of getting it.
Once diagnosed, most cancers can be treated in some way to reduce their impact, prolong life, or even eliminate them. The branch of medicine devoted to the study and treatment of cancer is oncology, and a doctor who practices in this area is known as an oncologist. The most common cancer treatments involve one or more of the following: surgery (operation to remove the tumor), radiation (x-rays and other high energy used to kill cancer cells and shrink tumors), and medication. Because the medications are chemicals aimed at the cancerous cells (neoplasms), this form of treatment is called antineoplastic chemotherapy. At times, chemotherapy and or radiation therapy may be given before the main treatment (usually surgery) to reduce the tumor size. This is known as neoadjuvant therapy, which helps to increase the overall chances of success of the main treatment. Likewise, chemotherapy and or radiation therapy can be administered after the main treatment (surgery or radiation), and this is known as adjuvant therapy. It is given to destroy any residual cancerous cells that may have been left behind from the main treatment and reduce the risk of recurrence.
In addition to chemotherapy, another approach in the treatment of cancer is the use of immunotherapy (or biotherapy). Immunotherapies are medications that target specific parts of the immune system to aid in its ability to detect cancer cells, amplify immune responses, slow cancerous growth, and eradicate cancerous cells. Immunotherapy can be given in conjunction with chemotherapy or alone depending on the disease being treated. Since this is a pharmacology text, we will focus on chemotherapy as well as some immunotherapies for the treatment of cancer.
Much of the cancer chemotherapy in current use is cytotoxic, meaning that it kills cells. As noted in Chapter 27, Bacterial Infections, the medications used to kill cells must be more harmful to the unwanted cells (whether bacterial or cancerous) they are intended to destroy than to the normal cells of the body. In general, cancer cells divide more rapidly than most normal cells, and many antineoplastic medications (as well as the radiation therapy mentioned above) target this difference. As a result, tumor cells are more sensitive than most normal cells to the actions of the medications used to treat cancer. Normal cells most likely to be affected by antineoplastic agents are the ones that reproduce the most frequently (scalp hair, white blood cells [WBCs], mouth, and GI lining); this accounts for some of the most common side effects (hair loss, neutropenia, oral ulcers, diarrhea).
Antineoplastic chemotherapy treatments work to disrupt the cell cycle in an attempt to cause enough changes in the cellular makeup that the cell cannot divide, or to damage the cellular makeup enough to cause the cell to die. (These changes can also affect normal cells, the reason for special handling precautions.) Some chemotherapeutic agents are cell-phase specific (meaning they act on cells at a specific stage of growth and division) while others can be given at any time in a cell’s life and cause these changes.
Antineoplastic chemotherapy must be precisely dosed to maximize its therapeutic activity and minimize its side effects. Body surface area (BSA) is a measurement of the external area of the body, generally expressed in square meters (m2) and most often calculated from a patient’s height and weight rather than actually measured. Because it is thought to be a more accurate indicator of the patient’s actual size than weight alone, it is used in dose calculations for dangerous drugs requiring extra precision, including many cancer chemotherapy agents.
Chemotherapy most often requires a combination of a number of drugs in addition to other treatments such as surgery and radiation therapy. Depending on the type of drug used, it may be administered by mouth, intravenously, or directly into the affected organ. Doses are generally calculated using BSA, resulting in more specific dosing. Antineoplastics are classified by the way they work and how they affect the cancer cell. Usually, chemotherapy will be prescribed as a regimen consisting of a combination of antineoplastic drugs of different types, with different mechanisms of action. We will begin with a discussion of the various classes of agents and move on to how they can be used together for the treatment of various cancers.
An alkylating agent works by binding to DNA, the genetic material of the cell. It interferes with the DNA replication necessary for the cell to grow and divide, slowing or stopping the growth of a tumor. Agents in this group are not cycle specific (see above); they can do their damage at any point in the cell’s life cycle. Their action is most evident in fast-growing and replicating cells, but this means they also suppress the cells of normal bone marrow. With increasing doses of alkylating agents, there is usually a corresponding increase in side effects, especially myelosuppression, an interference with the bone marrow’s production of blood cells and platelets. Other side effects common to alkylating agents include decreased appetite, hair loss (alopecia), mouth sores (mucositis), and diarrhea. With prolonged use, serious side effects of sterility and secondary cancers have been reported.
Among the first alkylating agents (and antineoplastic therapies overall) were the nitrogen mustards—derivatives of the poisonous gas used in World War I that were noted to suppress production of blood cells in the bone marrow of soldiers who had been exposed. These include chlorambucil, mechlorethamine, and melphalan, as well as two more commonly used agents, cyclophosphamide and ifosfamide. In addition to sharing the side effects common to the other alkylating agents, cyclophosphamide and ifosfamide have a relative emetogenic risk, meaning they may cause nausea and vomiting (N&V) proportional to their prescribed doses. Their most serious and characteristic side effect, however, is hemorrhagic cystitis, a damaging inflammation of the bladder that can be complicated by serious bleeding. For this reason, patients receiving these drugs are hydrated ahead of time with large volumes of intravenous (IV) and/or oral fluids to dilute the dangerous chemicals they produce, which are toxic to the bladder.
The cytoprotective agent (see Table 31-3) mesna, administered to reduce the damage to normal cells, reacts with the inflammatory byproduct of the alkylating agents to form a stable compound, which can be excreted without causing cystitis. It is always included in regimens containing ifosfamide, and sometimes used with cyclophosphamide therapy as well. Mesna has no antineoplastic activity and few significant side effects. There are no indications for its use either alone or to prevent side effects from other antineoplastics.
The dose of mesna is based on the dose of ifosfamide. Usually, an IV dose equal to 20% of the ifosfamide dose is administered prior to beginning the ifosfamide infusion and is followed either by additional 20% IV doses at 4 and 8 hours (total 60%) or 40% oral doses at 2 and 6 hours (total 100%). There are other dosing regimens, some even involving mesna mixed and administered with the ifosfamide in the same large-volume bag.
Ifosfamide is never administered without a concurrent order for mesna in the regimen. Mesna must precede or at least accompany the ifosfamide; giving it later reduces its effectiveness.
Mesna is not cytotoxic and handling it alone (without ifosfamide or cyclophosphamide) does not require any of the precautions necessary for hazardous drugs.
Another type of alkylating agent is a complex incorporating the heavy metal platinum to bind with DNA in the targeted cells. While all the medications in this class have the same mechanism of action, the part of the drug to which the platinum is attached influences the kinds of cancer each is used to treat, and the expected side effects. The original agent in this group, cisplatin, is indicated in treating cancers of the ovary, bladder, and testis, but has been used in regimens to treat many other types of cancers as well. It is considered highly emetogenic and doses are usually preceded by medications to prevent N&V with follow-up treatment over the next 3 to 5 days. Cisplatin can cause severe kidney damage, along with depletion of body potassium and magnesium. To accomplish dilution of the drug in the kidneys, patients generally receive large volumes of fluid both before and after doses. Dosing is adjusted downward for patients with poor kidney function.
Usual doses of cisplatin do not exceed 100 mg/m2; anything above that must be confirmed with the prescriber and/or against the protocol in use.
Patient may have orders for 1,000–2,000 mL of normal saline to be administered both before and after cisplatin doses; sometimes potassium chloride and magnesium sulfate are added to these to replace expected losses.
Compared to most other alkylating agents, cisplatin is less myelosuppressive, so decreases in WBCs and platelets are not usually as severe, though anemia may result from long-term dosing regimens. Cisplatin has, however, been linked to nervous system toxicities, including hearing loss and weakness, numbness, or pain in the hands and feet, termed peripheral neuropathy.
Carboplatin also incorporates platinum, and its mechanism of action is similar to that of cisplatin; it is indicated for ovarian cancer, but sometimes is used in treatment regimens for other neoplasms as well. It is less emetogenic, less neurotoxic, and less nephrotoxic than cisplatin but has a higher incidence of myelosuppression (with decreases in WBCs, red blood cells [RBCs], and platelets) and causes more hypersensitivity reactions.
Oxaliplatin is the newest agent of this group and is indicated for colon and colorectal cancers. Like cisplatin, it has been associated with peripheral neuropathy. Neither carboplatin nor oxaliplatin administration requires prehydration with large volumes of fluid. The trade names, dosage forms, routes of administration, usual doses, and indications for these and other alkylating agents (including bendamustine, carmustine, lomustine, busulfan, procarbazine, streptozocin, temozolomide, and thiotepa) are detailed in Medication Table 31-1 (Medication Tables are located at the end of the chapter).
Serious and even fatal hypersensitivity reactions (anaphylaxis) have been associated with administration of platinum compounds.
Needles and IV sets containing aluminum must not be used in preparation or administration of platinum antineoplastics, as they can react with the medication, causing inactivation and precipitation.
Oxaliplatin is incompatible with normal saline and must only be diluted in dextrose as any other diluent may cause it to precipitate.
LOOK-ALIKE/SOUND-ALIKE—Cisplatin and carboplatin are look-alike/sound-alike drugs.
Mrs. Sullivan must go to the oncology center every other Monday and Tuesday to get IV chemotherapy. One of the medications she receives is oxaliplatin. What must the pharmacy technician consider in preparing her doses?
An antimetabolite is a drug similar to natural cellular chemicals included in DNA and RNA. It works by inhibiting the synthesis of DNA, thus interfering with the division and functioning of cells, because its chemical resemblance enables it to be used by the cell in place of the molecule normally used in a given reaction but with a harmful result. This prevention of normal cell division and reproduction leads to programmed cell death, called apoptosis. Because antimetabolites are not specific to the functions of cancer cells, they are also cytotoxic to rapidly dividing healthy cells, and that is the basis of most of their side effects.2
The first group of antimetabolites is termed folate antagonists. When it was discovered that a diet with reduced levels of the B vitamin folic acid led to a decrease in leukemia cell counts, researchers worked to develop a drug treatment that would interfere with the functions of folates in the body. This led to the synthesis of methotrexate, which is chemically similar to folic acid and can replace it in the body processes that produce a form of folate that can be used during DNA synthesis. Methotrexate still plays a significant role as a treatment for sarcoma, leukemias and sometimes breast cancer. Methotrexate is very toxic at high doses. As noted earlier, normal cells are not immune from its effects, although tumor cells seem to retain it in higher concentrations than healthy ones. Methotrexate is less emetogenic than many other chemotherapeutic agents, although dose-related N&V can occur. Serious side effects include myelosuppression, as well as nephrotoxicity (kidney damage), central nervous system (CNS) toxicity, and liver toxicity.
Recall fromChapter 13that methotrexate is also used in the treatment of rheumatoid arthritis. Dosing and duration of therapy are different when it is used to treat cancer.
Methotrexate causes nephrotoxicity by precipitation in the renal tubules. The chance of this can be reduced by hydration, so some patients, especially those receiving high doses, may have orders for 3,000 mL/m2per day, as well as receiving alkalinizing agents to increase urinary pH. Some patients may receive an antidote, glucarpidase, which is a recombinant bacterial enzyme that hastens the metabolism of methotrexate into its inactive components, preventing toxic side effects.
Leucovorin (folinic acid) is the active form of folate in the body and may be administered along with the methotrexate to reduce the myelosuppression and some (though not all) other side effects associated with treatment. It does not appear to prevent some of the toxicities, including those to the liver and kidneys. The use of leucovorin in this way is sometimes termed leucovorin rescue.
Patients receiving methotrexate should avoid prolonged exposure to sunlight or sunlamps and avoid alcohol.
Leucovorin, also known as folinic acid or citrovorum factor and administered as the calcium salt, is not a hazardous substance and its preparation and administration do not call for any extra precautions.
Pemetrexed is another folic acid antagonist indicated for the treatment of malignant mesothelioma and some lung cancers and used in combination with cisplatin. It works by disrupting folate-dependent metabolic processes essential for the rapid growth of tumors. It is usually scheduled on the first day of a 21-day cycle, as one dose every 3 weeks. Common side effects include nausea, fatigue, and myelosuppression. Administration has also been associated with skin rash, and many patients are pretreated with an oral corticosteroid (often dexamethasone) the day before and the day of treatment, as well as the day after.
Another drug Mrs. Sullivan receives at the oncology center is IV leucovorin. What precautions are necessary when the pharmacy technician prepares and labels this medication?
Folic acid supplementation (alone or as part of a multiple vitamin) reduces pemetrexed toxicity, and patients are usually instructed to begin this a full week before the first pemetrexed dose. These patients also receive intramuscular (IM) vitamin B12 during the week before the first dose and every 9 weeks (with the scheduled pemetrexed dose) thereafter.
The third drug (in addition to the leucovorin and oxaliplatin) Mrs. Sullivan receives during her treatment sessions is 5-FU. Is the leucovorin considered a “rescue medication”?
Another group of antimetabolite agents are known as pyrimidine antagonists or analogs because they chemically resemble natural substances known as pyrimidines and replace them in the enzyme reactions that lead to DNA replication. These include fluorouracil (5-FU), capecitabine, and cytarabine. 5-FU is one of the older chemotherapy agents still in use and, since it is distributed generically, is fairly inexpensive (although it has recently been subject to intermittent shortages due to manufacturing delays). 5-FU is used for the treatment of cancers of the breast, pancreas, stomach, colon, skin, and rectum. 5-FU may be applied to the skin via a cream to treat actinic keratoses and is sometimes used for basal cell carcinomas (a type of skin cancer) associated with chronic, prolonged sun exposure and sun damage. Ironically, leucovorin, the agent that is used to “rescue” patients from the effects of methotrexate, is often combined with 5-FU to increase its potency (and, as a result, some of its side effects, too). The most prominent side effects of 5-FU are related to the GI tract, especially lesions of the mouth, known as mucositis, and diarrhea. While it is less likely to cause the most common chemotherapy-associated reactions (nausea, vomiting, and alopecia) compared to many agents, it has been associated with myelosuppression, eye problems, and skin conditions. High doses can also cause cardiac symptoms.
Both 5-FU and capecitabine interact with warfarin to increase its anticoagulant effects and the danger of bleeding if INR (international normalized ratio) is not monitored and doses adjusted. Patients taking phenytoin may also require a decrease in dosage to avoid toxic phenytoin blood levels.
5-FU is sometimes administered by IV infusion (diluted in a large-volume IV bag of normal saline or 5% dextrose) and sometimes ordered as an IV injection (given undiluted and often prepared in the pharmacy for dispensing in a syringe).
Capecitabine is indicated for breast and colorectal cancer. It is a modified form of 5-FU for oral administration and is converted by the body’s enzymes to 5-FU, so it has similar actions and side effects, although it is associated with less myelosuppression. Cytarabine (also known as Ara-C and cytosine arabinoside) is another older antimetabolite still in use. It is a cycle-specific agent, meaning that its action is restricted to proliferating cells. It is indicated for the treatment of leukemias and lymphomas. Side effects include myelosuppression, alopecia, diarrhea, mucositis, rash, and conjunctivitis. Some patients experience flu-like symptoms (muscle pains, fever). It is moderately emetogenic, and neurologic toxicities have been noted.
Gemcitabine is a pyrimidine antimetabolite related to cytarabine and indicated for pancreatic, breast, and some lung cancers. It has fewer side effects than cytarabine and is considered less emetogenic, but it still may cause skin conditions and flu-like symptoms. Another pyrimidine is floxuridine, used to treat cancers of the GI tract.
When cytarabine is being prepared for intrathecal (spinal) administration, only the preservative-free solution (labeled PF) or the liposomal suspension can be used. Technicians must be sure to choose the correct preparation as errors could be fatal.
The final group of antimetabolites is known as purine analogs, after the nucleic acids (purines) they resemble and with which they interfere in cellular processes. These include mercaptopurine, thioguanine, fludarabine, cladribine, and pentostatin. They are used primarily in the treatment of leukemias and are detailed in Medication Table 31-1.
Antitumor (or antineoplastic) antibiotics are derived from microorganisms. They are capable of disrupting cellular functions, primarily blocking cell growth by inhibiting DNA synthesis, and delaying or inhibiting cell division. The anthracycline antibiotics are derived from a fungus. Doxorubicin and daunorubicin are the natural fungal products, while idarubicin and epirubicin are chemically similar compounds.3 Inside dividing cells, they block important enzymes (topoisomerases) to produce DNA breaks in cells exposed to them, resulting in apoptosis. Anthracyclines are used in the treatment of a variety of cancers, including leukemias (doxorubicin, daunorubicin, idarubicin), breast cancer (doxorubicin and epirubicin), and Hodgkin’s disease/lymphomas, sarcomas, neuroblastoma, thyroid, lung, ovarian, breast, gastric, and bladder cancer (doxorubicin).
The brand name of doxorubicin is Adriamycin, and it represents the A in many of the cancer chemotherapy regimens known by their acronyms, such as the breast cancer regimen AC (Adriamycin and cyclophosphamide).
The anthracyclines may be highly or moderately emetogenic depending on the dose, and common side effects include myelosuppression, mucositis, and alopecia. The anthracyclines are vesicants, which means they can cause necrosis (death) to living tissue exposed to these agents. For this reason, they must be administered by skilled personnel, and any escape of the medication outside of the vein and into the surrounding tissue, known as extravasation, must be treated immediately to avoid permanent damage.
Anthracyclines may cause red-orange discoloration of the urine, provided they are chromophores, or chemicals that produce an intense color because of their underlying molecular composition.
While these antineoplastics have long been used to treat a variety of cancers, they have an additional toxic effect that does not appear to be antineoplastic but is, instead, somewhat selective for cardiac muscle tissue. The cardiotoxicity they produce can be early (acute) or late (delayed). The acute type takes the form of dangerous arrhythmias or pericarditis (inflammation of the tissue surrounding the heart), which can develop during treatment or shortly afterward; it is not necessarily related to the dose. The cardiotoxicity and vesicant properties of the anthracyclines are thought to be related to the creation of free radicals, which are molecular fragments that are highly reactive and have the potential to be damaging to the body’s normal cells, particularly the heart muscle.4 The chronic form can be delayed for months, and its incidence is related to the total (accumulated) dose the patient received during the course of therapy and can ultimately result in congestive heart failure.
Cardiac function is monitored in patients receiving these agents, and immediate discontinuation of treatment may diminish the risk of serious heart damage.
With doxorubicin therapy, lifetime maximum dosages are limited to 450–550 mg/m2to reduce the risk of delayed cardiac toxicity. Good recordkeeping is vital to documenting the accumulated dose.
Dexrazoxane is a cytoprotective agent (see Table 31-3) that reduces the damage by free radicals created in anthracycline exposure. When used as a cardiac protectant, it is administered prior to chemotherapy as a dose 10 times the dose of doxorubicin. If given to reduce tissue damage from extravasation, the dose is based on BSA and administered on 3 consecutive days. While dexrazoxane is a specific antidote for doxorubicin, it has been used with other anthracyclines.4
Doxorubicin and daunorubicin are also available as liposomal formulations, with the active drug encapsulated in a layer of phospholipids, which lengthen duration of activity and presumably facilitate entrance selectively into tumor cells. This enables lower dosing, with a reduced risk of both vesicant effects and cardiotoxicity.
Unlike many other medications considered cytoprotectives and antidotes, dexrazoxane is a hazardous substance and must be handled, prepared, and dispensed as such and reconstituted using the supplied diluent (sodium lactate).
LOOK-ALIKE/SOUND-ALIKE—Conventional and liposomal dosage forms of doxorubicin and daunorubicin are not interchangeable, but the generic names/active ingredients are similar so care must be taken to select the right product for dispensing.
Bleomycin is an antibiotic agent used in combination chemotherapy regimens to treat Hodgkin’s lymphoma and testicular and ovarian cancers. It is only mildly emetogenic and not associated with myelosuppression. Common side effects of this agent include hypersensitivity reactions, flu-like symptoms, and mucositis. Its most serious toxicity is lung damage. Mitoxantrone is an antibiotic agent used to treat prostate cancer and leukemia. (Recall from Chapter 6 that it is also indicated for multiple sclerosis.) Compared with the anthracyclines, mitoxantrone is associated with less heart damage, nausea, and vomiting; it is not a vesicant (although it may cause vein irritation). Side effects are myelosuppression, alopecia, and mucositis. The antitumor antibiotics mentioned above and others are detailed in Medication Table 31-1.
Mitoxantrone may cause a blue-green discoloration of the urine.
In addition to the antibiotics discussed above, some other cytotoxins used to treat cancer are natural products. These agents are derived mostly from plants and include the vinca alkaloids and taxanes, which are active against a wide variety of tumors. They are considered antimitotics because they interfere with mitosis (cell division). They are also known as microtubule-targeting agents because the cell component with which they interfere is the microtubule. The vinca alkaloids are obtained from the Vinca rosea (periwinkle) plant, which was first thought to be useful in the treatment of diabetes. They act by interfering with the dividing cell’s separation of chromosomes in preparation for replication; this action and their disruption of other processes results in apoptosis in cells exposed to them. Vincristine can be used for certain leukemias, lymphomas, and sarcomas. Vinblastine can be used used in testicular cancer and lymphomas, as well as Kaposi’s sarcoma associated with HIV infection. Vinorelbine is another agent in this class, although it is a synthetic (not natural) analog of the periwinkle derivatives. It is indicated in the treatment of some lung cancers and is also used to treat malignancies of the breast, cervix, and uterus. Vinca alkaloids, while having a relatively low emetogenic effect, are vesicants and are associated with mucositis and myelosuppression. Vinca alkaloids, particularly vincristine, can cause nervous system toxicities, including peripheral neuropathy and damage to motor, sensory, cranial (head), and autonomic nerves. These toxicities result in additional problems including unpleasant sensations, problems with GI motility, facial muscle spasms, and urinary retention. Other toxicities include impaired liver function, hearing, and vision.
The taxanes are another class of naturally derived anticancer agents that bind to internal cell structures, rendering them nonfunctional, inhibiting cell division, and causing apoptosis. Paclitaxel was first extracted from the bark of the Pacific yew (Taxus brevifolia, thus the taxane designation) during an NCI initiative for screening potentially valuable plant substances.5 Docetaxel was synthesized from an extract of European yew needles and has activity similar to paclitaxel. Taxanes are used extensively for breast, ovarian, lung, head, and neck tumors.
Vinca alkaloids have been associated with fatalities when accidentally administered intrathecally (spinal administration). Because the doses are often small volumes given as IV injections, they have been traditionally prepared and dispensed in syringes, which can make them seem like intrathecal rather than IV doses. Vinca alkaloids must carry the warning FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.
Paclitaxel and docetaxel are generally well tolerated and only mildly emetogenic. They are myelosuppressive and associated with hair loss (sometimes over the whole body) and peripheral neuropathy. Paclitaxel can cause muscle and joint aches, mucositis, and cardiac irregularities. Premedication with diphenhydramine, steroids (such as dexamethasone), and a histamine-2 blocker (such as ranitidine) is required before doses of conventional paclitaxel to prevent hypersensitivity reactions, but another dosage form binding the drug to a protein eliminates the need for this. Docetaxel sometimes causes a rash (especially on the hands and arms) and nail disorders. Steroids (usually oral) are generally begun the day prior to a docetaxel dose to reduce fluid retention and prevent edema. Taxanes should only be diluted in PVC-free IV bags and administered via PVC-free tubing due to the risk of leaching plasticizers found within PVC-containing equipment (eg, diethylhexyl phthalate, DEHP).
The protein-bound form of paclitaxel (Abraxane) has different functional properties than the conventional drug. It must not be substituted for other paclitaxel formulations.
A plant substance known as podophyllotoxin has been chemically modified to produce antineoplastic medications with a mechanism of action similar to the anthracycline antibiotics discussed earlier. Etoposide (VP-16) is used as an IV or orally administered treatment for testicular and lung cancers, and teniposide is administered IV for childhood leukemias. These drugs do not have the cardiac toxicities associated with the anthracyclines but are moderately emetogenic and cause alopecia, mucositis, and hypersensitivity reactions.
Another group of agents derived from plants are the camptothecins. These drugs also block a topoisomerase (although not the same one as the anthracyclines and podophyllotoxins) and are used in the treatment of colon cancer (irinotecan) and ovarian cancer (topotecan). Drugs from this group, along with their brand names, pronunciations, routes of administration, indications, and usual doses, can be found in Medication Table 31-1.
LOOK-ALIKE/SOUND-ALIKE—Paclitaxel and docetaxel are look-alike/sound-alike drugs.
Hormonal agents have been used to treat several types of cancers. Hormonal therapy interferes at the cellular level with growth stimulatory receptor proteins. The mechanisms of action, however, may differ from one agent to the next. Hormone therapy usually consists of drugs or surgery to decrease the production of male hormones (androgens) or female hormones (estrogens) thereby stopping or limiting the growth of prostate or breast cancer. These cancers are hormone-sensitive or hormone-dependent, meaning that their growth is related to the presence or stimulation of androgens or estrogens. Hormone therapy has the advantage of being specific for tissues that are responsive to hormonal effects and can stop or slow the growth of cancers without having cytotoxicity.
Androgens, estrogens, and agents that mimic or block them have been used in the therapy of malignancies of the prostate, breast, and endometrium (uterine lining). Tests are available to show whether cancer cells have estrogen, progesterone, or testosterone receptors to enable a choice of therapy likely to block the way these hormones stimulate the cancer growth.
There are several groups of hormonal agents used in cancer treatment. The aromatase inhibitors work by blocking the enzyme aromatase. Aromatase enables the body to turn natural androgen into small amounts of estrogen. Three commonly used aromatase inhibitors are anastrozole, exemestane, and letrozole. They are used to treat breast cancers shown to have estrogen receptors (ER-positive) and only in postmenopausal women (whose primary source of estrogen is the aromatase-mediated reaction, unlike premenopausal women whose ovaries produce estrogen without the intervention of aromatase). The major side effects of these agents are hot flashes, muscle and joint pain, headache, fatigue, hyperlipidemia, and changes in liver enzyme levels.
The aromatase inhibitors are also used to treat ovulation disorders; that role was discussed inChapter 11.
Another type of hormonal therapy is termed antiestrogen and involves interfering with the actions of natural estrogens, often by blocking the receptors to which they attach. This group (used to treat ER-positive breast cancer) includes tamoxifen (also used to prevent breast cancer), fulvestrant, and toremifene (also used for endometrial cancers). Megestrol is a progestin (see Chapter 11) that interferes with normal hormonal activity and is indicated for the treatment of breast and endometrial cancers. Antiestrogens cause hot flashes, fluid retention, weight changes, and depression. Antiandrogens (flutamide, nilutamide, bicalutamide, abiraterone, and abarelix) block the testosterone receptors of prostate cancer cells. Their actions were discussed in detail in Chapter 11. Hormonal cancer treatments are listed in Medication Table 31-1.
Additional hormonal therapies include luteinizing hormone-releasing hormone (LHRH) analogs (goserelin, leuprolide) and antagonists (degarelix). LHRH agents (also known as gonadotropin-releasing hormone [GnRH] agents) work by binding to receptors within the pituitary gland, ultimately halting the production of testosterone or estrogen through either negative feedback (analogs) or direct blockade (antagonist). These agents are used in advanced breast and prostate cancers. LHRH analogs and antagonists can cause fluid retention, gastrointestinal issues, decreased libido, impotence, and hot flashes.
Megestrol is also used to stimulate the appetite of oncology patients and thus promote weight gain. When used for this indication, doses are generally much higher than those prescribed for the treatment of breast or endometrial cancer.
Small Molecule Targeted Agents
Intracellular signaling pathways allow cancerous cells to signal growth and trigger division. These pathways rely on enzymes known as kinases that work to transfer a phosphate group from adenosine triphosphate (ATP, known as the energy currency of the cell) to various proteins within the cell, a process known as phosphorylation. This acts as a switch to turn on signaling cascades to start such cellular events as growth and division. At times, these kinases can become mutated and left in the “on” position, causing rapid, uncontrolled growth. Kinase inhibitors work by blocking the site where ATP would normally bind, therefore preventing the switch from turning on. There are various types of kinase inhibitors and most inhibit more than one specific kinase, which leads to stray side effects depending on where they are found. Gene rearrangement tests are conducted to check for the presence of kinase mutations to determine whether a patient may benefit from a specific kinase inhibitor. Almost all kinase inhibitors are taken orally.
In some circumstances, cancerous cells may become resistant to the effects of a kinase inhibitor by reconfiguring the site at which they bind, ultimately preventing the drug from working. This has led to the development of different generations of kinase inhibitors that are able to overcome the resistance developed by certain cancerous cells. For example, crizotinib is a first-generation kinase inhibitor of anaplastic lymphoma kinase (ALK), which is found in certain lymphomas and lung cancers. Over the course of crizotinib therapy, some patients may develop resistance to its effects, at which time they are placed on second or third generations of ALK inhibitors (alectinib, brigatinib, ceritinib, and lorlatinib) that bypass the developed resistance and continue to work accordingly. More information on specific kinase inhibitors and their associated side effects are found in Medication Table 31-2.
Biologic therapies are treatments using substances made from living organisms.1 Recombinant DNA technology has enabled the manufacture of these substances (or agents with similar action and structure) in laboratories and manufacturing facilities. The type of biologic therapy most frequently used in cancer treatment is immunotherapy, which can actually boost, direct, or restore the body’s ability to fight neoplasms.
Monoclonal antibodies are specific antibodies (introduced in Chapter 30) directed against antigens located on the surfaces of tumor cells. Several agents of this type are available to treat various cancers. Because each has a different and very specific target, side effects vary, but fever, chills, and headache occur with many of them, and several are commonly administered after premedication with some combination of acetaminophen, an antihistamine (usually diphenhydramine), and/or a corticosteroid (often dexamethasone). These therapies are identified by the –mab suffix in their names (ie, rituximab, cetuximab, atezolizumab, etc.). Their names also describe the composition of the monoclonal antibody, as follows: (1) chimeric, or constructed utilizing cellular machinery from another mammal—a mouse in most cases (as noted with the –ximab suffix); (2) partially human (ie, humanized), or constructed with nonhuman cellular machinery though more similar in structure to natural human monoclonal antibodies (as noted with the –zumab suffix); and (3) fully human, or constructed with viral machinery that encodes exact copies of human antibodies (as noted with the –umab suffix).6 The derivations of each monoclonal antibody can help to determine the risk of infusion reactions as those derived from outside sources (ie, chimeric) have a greater chance of causing infusion-related reactions.6 Some monoclonal antibodies have been associated with serious, even fatal, infusion or other reactions. Monoclonal antibodies used to treat cancer, with their pronunciations, brand names, usual doses, and indications, are listed in Medication Table 31-2.
Monoclonal antibodies are biological products that maintain their activity only when handled, stored, and prepared exactly as directed. Most bear warnings that vials and solutions must be handled gently or even the prohibition “DO NOT SHAKE” as shaking can render them inactive.
Rituximab is a chimeric monoclonal antibody that is known to cause frequent infusion-related reactions (including fatal incidences) particularly with the first infusion. It’s strongly recommended that individuals be pretreated with acetaminophen and an antihistamine prior to infusion.
LOOK-ALIKE/SOUND-ALIKE—Rituximab and cetuximab are look-alike/sound-alike drugs.
Cytokines are naturally occurring substances in the immune system. Some suppress immune response, while others stimulate it. Interferons (IFNs) are cytokines that suppress cell proliferation and increase immune system activity against target cells. Their use as antivirals is discussed in Chapter 28, but they are also used in the treatment of some cancers, including hairy cell leukemia, melanoma, chronic myeloid leukemia, and AIDS-related Kaposi’s sarcoma.
Interleukins are cytokines that stimulate interferon production as well as increasing the activity of “killer” cells in the immune system. These actions can be directed against tumor cells. While many interleukins have been identified, interleukin-2 (IL-2) is the most widely studied in cancer treatment. Recombinant IL-2 is indicated for the treatment of renal cell carcinoma and metastatic melanoma. A related product, denileukin diftitox combines human IL-2 with portions of the diphtheria toxin molecule and causes apoptosis of certain cells. It is indicated for the treatment of some lymphomas.
As previously mentioned, a subclass of biologic therapy known as immunotherapies has been pivotal in the current approach to treating cancer. Immunotherapies work to invigorate the inherent immune system to seek and destroy cancerous cells by upregulating the body’s own immune cell activities (particularly T cells). One such target is known as programed cell death protein 1 (PD-1), which is found on normal healthy cells, which ultimately downregulates immune system responses by acting as an inhibitory signal (similar to a key turning off a car).7 Naturally, PD-1 functions to reduce overreaction in the immune system when it encounters various stimuli. However, PD-1 can be used by cancer cells to hide and evade immune responses that would normally eliminate such abnormal cells. Blocking PD-1 proteins on cancer cells from interacting with immune cells (T and B cells) allows for the detection of cancer cells and triggering of cancer cell death. Immunotherapies may be used as an individual treatment or as part of a regimen in multiple cancers. Examples of such agents and their uses are detailed in Medication Table 31-2.
Many biotherapies now have available biosimilars that are mistakenly referred to as “generics.” Biosimilars are biological products that are highly similar to products already approved by the Food and Drug Administration (FDA), and do not have clinically meaningful differences related to their safety and efficacy.6They are not referred to as generics because they are large protein structures and, given their complexity is challenging to make exact copies. The Purple book is a compendium of all known FDA approved and available biosimilars.8
Antineoplastic Therapy Regimens
The antineoplastic agents discussed in this chapter are seldom used alone. Cancer chemotherapy generally consists of a regimen, or combination, of medications in specific dose ranges and intervals designed to increase the likelihood of successful therapy, while decreasing the severity of the side effects. Medications from different groups, with different mechanisms of action, are chosen to attack the cancer cells in multiple ways, either simultaneously or sequentially.
There are numerous regimens (with more being developed in clinical trials) available, each of which has been studied for use in specific situations. Some cancer therapy is aimed at a cure, with complete eradication of the cancer. Other therapies are considered palliative and are used to diminish symptoms or even prolong life in patients whose cancers are unlikely to respond to the extent of complete cure. Some antineoplastic regimens are termed adjuvant therapy and are administered to prevent recurrence of disease that has been treated with surgery or radiation. These are often administered cyclically: weekly, every 21 days, monthly, or at some other customized interval (sometimes during only one day of the cycle and sometimes on two or more consecutive days). The interval scheduling is planned in part to allow the bone marrow to recover from a chemotherapy-induced nadir (the point at which blood cell counts are at their lowest). Most cancer treatment regimens and their specific indications can be found in the National Comprehensive Cancer Network® (NCCN) guidelines.9 The NCCN guidelines are the most up-to-date treatment algorithms and are used extensively in oncologic practices in North America.9
Mrs. Sullivan receives three different antineoplastics and has to visit the oncology center 2 days every other week. Why does she need so many drugs and doses?
Mrs. Sullivan had her cancer removed before beginning antineoplastic medications. What is the term for the IV treatment she is receiving at the oncology center?
Chemotherapy regimens are sometimes given distinctive names, such as the Roswell Park Regimen (5-FU with folinic acid) for colorectal cancer, or they simply list the included drugs, such as the carboplatin/pemetrexed regimen for malignant mesothelioma. Many are acronyms that incorporate the first letters in the names (sometimes brand, sometimes generic) of the drugs included, such as FOLFOX6 (folinic acid/fluorouracil/oxaliplatin) for colorectal cancer; TAC (Taxotere–docetaxel/Adriamycin-doxorubicin/cyclophosphamide) for breast cancer; or CHOP (cyclophosphamide/hydroxydaunorubicin–doxorubicin/Oncovin–vincristine/prednisone) for lymphoma.
Side Effect Management
As emphasized throughout this chapter, antineoplastic medications have many significant side effects. Because therapy must often continue for long periods of time to achieve the goals of treatment, management of these side effects is crucial to both the patient’s quality of life and the ability to continue the treatment. Side effects frequently associated with chemotherapy and treated with pharmacologic intervention are N&V, mucositis, and myelosuppression.
Prevention and control of N&V are important parts of many chemotherapy regimens. N&V are unpleasant in themselves but can result in serious consequences, including nutritional depletion, anorexia, deterioration of patients’ physical and mental status, decreased ability to function, and withdrawal from potentially useful and curative treatment. Emetogenic potential varies with the agents, and antiemetic therapy is chosen and dosed based on the antineoplastics used. Patients most at risk for hard-to-control N&V from chemotherapy are those who are under 50 years old, female (particularly those with persistent N&V symptoms during pregnancy), those who experienced uncontrolled symptoms during an earlier treatment, those who have a history of motion sickness, or those who have always abstained from alcoholic beverages. Antiemetics and their use in chemotherapy are discussed extensively in Chapter 21, as well as in the NCCN antiemesis guidelines for supportive care.9
Mrs. Sullivan’s physician has ordered a dose of ondansetron 8 mg by mouth twice daily in the weeks she receives chemotherapy. What is the purpose of this additional medication?
The mucosal lining of the GI tract, including the oral mucosa, has a rapid cell turnover rate and is thus highly susceptible to the toxic effects of cytotoxic agents. Oral mucositis describes inflammation of the oral mucosa; when this occurs, the oral cavity becomes red and swollen. Mucositis is managed with topical anesthetics (eg, viscous lidocaine, benzocaine gels, and mouthwash solutions containing diphenhydramine). Kaolin/pectin agents can be used to form a protective barrier and give relief, as well. If oral lesions become irritated or infected, additional management may be indicated. Some options are discussed in Chapter 36.
Mrs. Sullivan received chemotherapy on Monday and Tuesday. On Friday, she comes to the pharmacy with a prescription for her sore mouth. Why might her mouth be so swollen? What might the oncologist have prescribed?
Myelosuppression, an interference with the bone marrow’s functions, especially the production of blood cells and platelets, is one of the most common toxicities limiting the dose or continuation of therapy for antineoplastic agents. Neutrophils (detailed in Chapter 25) have a relatively short lifespan and are among the first type of cell to be depleted during therapy with myelosuppressive agents; when their count falls too low, patients suffer from neutropenia and are more susceptible to infection. This condition and its treatment are discussed in Chapter 26.
There are many additional adverse effects associated with antineoplastic chemotherapy. It is not unusual for patients receiving antineoplastics to receive preventive medications or to require treatment for the side effects; the prevention or treatment will vary with the regimen being used.
Handling Cytotoxic Medications
Cytotoxic medications and some other antineoplastic agents are hazardous substances, and exposure to them during handling, storage, preparation, delivery, administration, and disposal can pose health risks to pharmacy and medical personnel. These risks include cancer (carcinogenicity), damage to a developing fetus (teratogenicity), fertility impairment (reproductive toxicity), organ toxicity, and damage to DNA (genotoxicity).
Personal protective equipment (PPE), including appropriate gloves, long-sleeved gowns with closed fronts and fitted cuffs, eye and face protection, and shoe coverings, should be worn during the preparation of hazardous agents.10 The preparation and manipulation of these products in the pharmacy should be accomplished in a closed environment such as a biological safety cabinet or a barrier isolator. Procedures must be in place to treat accidental exposures, and equipment and supplies to clean up after spills must be readily available.
USP General Chapter provides standards for the safe handling of hazardous drugs to minimize the risk of exposure to healthcare personnel, patients, and the environment. Its standards apply to all healthcare personnel who receive, prepare, administer, transport, or otherwise come in contact with hazardous drugs and all the environments in which they are handled.10
Mrs. Sullivan’s medications include oxaliplatin, leucovorin, 5-FU, ondansetron, and viscous lidocaine. Which of these medications requires special handling, labeling, or disposal precautions? Why?
Cytotoxic preparations dispensed from the pharmacy should always bear a label warning those who will handle or administer them to wear gloves and dispose of them properly. Waste material from preparation and administration must be placed in puncture-proof containers with sealed lids labeled with an appropriate warning.10
Not all antineoplastic chemotherapy is considered hazardous, but technicians must determine ahead of time what precautions are indicated for the medications they are handling.
Cancer is a disease state in which abnormal cells divide without control and are able to invade other tissues. It can result in serious illness and death, and there are a variety of treatments, including surgery, radiation, and medication. Pharmacotherapy for cancer consists of agents that are intended to kill cancer cells and/or prevent them from multiplying or to enhance the body’s ability to fight the disease. Agents used in chemotherapy frequently have serious side effects, which may limit the administration of an effective dose, and must be managed appropriately. Many of the therapies are hazardous substances and require special handling, labeling, and disposal.
The author wishes to acknowledge and thank Allen L. Horne, RPh, author of this chapter in the first edition of this book.
WellsteinA.General Principles in the Pharmacotherapy of Cancer. In: BruntonLL, KnollmanBC, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 14e. McGraw Hill; 2022. Accessed July 28, 2022 https://accesspharmacy-mhmedical-com.neomed.idm.oclc.org/content.aspx?bookid=3191§ionid=266700746.)| false
MesserschmidtJL, PrendergastGC, Messerschmidt GL.How cancers escape immune destruction and mechanisms of action for the new significantly active immune therapies: Helping nonimmunologists decipher recent advances. Oncologist. 2016;21(2):233–243. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746082. Accessed June 10, 2022.
MesserschmidtJL, PrendergastGC, Messerschmidt GL.How cancers escape immune destruction and mechanisms of action for the new significantly active immune therapies: Helping nonimmunologists decipher recent advances. Oncologist. 2016;21(2):233–243. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746082. Accessed June 10, 2022.)| false
Ado-trastuzumab emtansine (a do tras TU zoo mab em TAN seen)
Monoclonal antibody-antineoplastic complex
3.6 mg/kg every 3 weeks
Afatanib (a FA ti nib)
40 mg once daily
Aldesleukin (IL-2) (al des LOO kin)
Biological response modifier
Powder for reconstitution
600,000 International Units/kg every 8 hours
Renal cell carcinoma (RCC), melanoma
Alectinib (al EK ti nib)
Enzyme inhibitor (2nd generation)
600 mg twice daily
Alemtuzumab (al em TOOZ oo mab)
Solution (preservative free)
3 mg/day increased to 30 mg/dose
Lymphomas, prolymphocytic leukemia
Alpelisib (AL pe LIS ib)
300 mg once daily
Atezolizumab (ah TEZ oh liz U mab)
Flat dose of 840 mg every 2 weeks OR 1,200 mg every 3 weeks OR 1,680 mg every 4 weeks
Breast, lung, or urothelial cancer
Axitinib (ax I ti nib)
5–10 mg twice daily
RCC, thyroid cancer
Belinostat (be LIN oh stat)
Solution (preservative free)
1,000 mg/m2 once daily on days 1–5 every 21 days
Peripheral T-cell lymphoma
Bevacizumab (be va SIZ yoo mab)
Avastin, Mvasi, Zirabev, Alymsys
Solution (preservative free)
5 or 10 mg/kg every 2 weeks
Colorectal cancer, NSCLC, glioblastoma, RCC
Bexarotene (bex AIR oh teen)
Cutaneous T-cell lymphoma
Binimetinib (bin I ME ti nib)
45 mg twice daily
Colorectal cancer, melanoma
Blinatumomab (blin a TOOM oh mab)
Dose based on weight if ≥45 kg (fixed dose) = Minimal residual disease positive (MRD+): 28 mcg on days 1–28 of 6 week treatment cycle; Relapsed/refractory (RR): 9 mcg daily on days 1–7 followed by 28 mcg days 8–28 of 6 week treatment cycle.
Dose based on BSA if 45 kg = Minimal residual disease positive (MRD+): 15 mcg/m2/day (max 28 mcg/day) as a continuous infusion on days 1–28 of 6 week treatment cycle; Relapsed/refractory (RR): 5 mcg/m2/day (max 9 mcg/day) days 1–7 followed by 15 mcg/m2/day (max 28 mcg/day) days 8–28 of 6 week treatment cycle
Bortezomib (bor TEZ oh mib)
Powder for reconstitution
Multiple myeloma, lymphoma
Bosutinib (boe SUE ti nib)
400 mg or 500 mg once daily
Brentuximab vedotin (bren TUX i mab ve DOE tin)
Antibody drug conjugate, monoclonal antibody
Powder for reconstitution
1.2–1.8 mg/kg every 2 or 3 weeks
Hodgkins lymphoma, peripheral T-cell lymphoma
Brigatinib (bre GA ti nib
Enzyme inhibitor (2nd generation)
180 mg once daily
Cabozantinib (ka boe ZAN ti nib)
60–140 mg once daily
Hepatocellular carcinoma, RCC, thyroid cancer
Carfilzomib (car FILLS oh mib)
20 mg/m2 days 1 and 2, if tolerated increased to 27 mg/m2 OR 36 mg/m2 OR 56 mg/m2 OR 70 mg/m2
Multiple myeloma, Waldenstrom macroglobulinemia
Ceritinib (Se RI ti nib)
Enzyme inhibitor (2nd generation)
450 mg once daily
Cetuximab (se TUX i mab)
Initial dose of 400 mg/m2 followed by weekly maintenance dose of 250 mg/m2
Colorectal cancer, squamous cell carcinoma
Copanlisib (koe pan LIS ib)
60 mg on days 1, 8, and 15 of a 28-day treatment cycle
Crizotinib (kri ZO ti nib)
Enzyme inhibitor (1st generation)
250 mg twice daily
Dabrafenib (da BRAF e nib)
150 mg twice daily
Melanoma, NSCLC, thyroid cancer
Dacomitinib (DAK oh MI ti nib)
45 mg once daily
Daratumumab (dar a TOOM ue mab)
16 mg/kg once weekly initially
Dasatinib (da SA ti nib)
100 mg once daily
Chronic myelogenous leukemia (CML)
Dinutuximab (din ue TUX i mab)
17.5 mg/m2 for 4 consecutive days for maximum 5 cycles
Durvalumab (dur VAL ue mab)
10 mg/kg once every 2 weeks
NSCLC, urothelial cancer
Duvelisib (DOO ve LIS ib)
25 mg twice daily
CLL, follicular lymphoma
Elotuzumab (el oh TOOZ ue mab)
10 mg/kg once weekly initially
Enasidenib (en a SID a nib)
100 mg once daily
Acute myeloid leukemia
Encorafenib (en koe RAF e nib)
300 mg or 450 mg once daily
Colorectal cancer, melanoma
Erdafitinib (er da FI ti nib)
8 mg once daily and increase to dose to 9 mg based on tolerability
Erlotinib (er LOE ti nib)
150 mg once daily
NSCLC, pancreatic cancer
Everolimus (e ver OH li mus)
10 mg once daily
Advanced RCC, breast cancer, subependymal giant cell astrocytoma (SEGA), pancreatic neuroendocrine tumors, prophylaxis of organ rejection