THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

19. Oncology - J. Aubrey Waddell, PharmD, FAPhA, BCOP Jaclyn S. King, PharmD

19-1. Overview

Definition

Oncology can be defined as the science dealing with the etiology, pathogenesis, and treatment of cancers (synonymous with malignant neoplasms). It encompasses more than 100 different diseases that share characteristics of uncontrollable cell proliferation, invasion of local tissues, and metastases (e.g., spread from original site).

In the United States, men have roughly a one-intwo cumulative lifetime risk of developing cancer and women have a one-in-three risk. In 2009, approximately 1,479,350 new cases of cancer will be diagnosed, and about 562,340 cancer deaths will occur. The most common types of cancer are prostate, lung, and colorectal in men and breast, lung, and colorectal in women.

Classifications

Neoplastic malignancies arise from four tissue types (epithelial, connective, lymphoid, and nerve) and are classified on the basis of this origin.

Table 19-1 lists the tissue origin of each type of malignancy and the corresponding medical terminology.

Clinical Presentation

The first signs and symptoms of cancer (solid tumors) develop when the tumor has grown to approximately 109 cells (1 cm in diameter or 1 g mass). The type of cancer determines the presentation of signs and symptoms, which vary widely across tumor types.

Positive screening tests (see Section 19-3) or generalized signs of anorexia, fatigue, fever, weight loss, and anemia must also be evaluated. Boxes 19-1 and 19-2 show the American Cancer Society's seven warning signs of cancer for adults and the warning signs for children.

Pathophysiology and Etiology

The following factors promote cancer:

• External factors: Tobacco, chemicals, radiation, infectious organisms, and diet

• Internal factors: Genetics, hormones, and immune conditions

Development of cancer is genetically regulated and is a multistage process:

• Initiation: Normal cells are exposed to chemical, physical, or biological carcinogens. Such exposure results in irreversible damage, genetic mutations, and selective growth advantages.

• Promotion: Reversible environmental changes favor the growth of the mutated cells.

• Transformation: The cells become cancerous.

• Progression: Additional genetic changes occur, resulting in increased cancerous proliferation. Tumors invade local tissues, and metastasis occurs.

Genetic alterations are necessary for the development and growth of cancer. Some of the most common are the following:

• Oncogenes promote growth advantages in mutated cells and cause excessive proliferation (e.g., ras, c-myc).

• Inactivation of tumor suppressor genes (TSGs) results in inappropriate cell growth, because TSGs normally regulate the cell cycle (e.g., p53).

[Table 19-1. Tissue Origin of Malignant Tumor Types]

• Anti-apoptotic genes are activated (e.g., bcl-2).

• DNA (deoxyribonucleic acid) repair genes experience reduced activity.

Malignant tumor cells do not resemble their tissue of origin (in contrast to benign tumors). They are unstable and are incapable of performing normal cell functions.

Diagnostic Criteria

A sample of suspected malignant tissues or cells is needed for a definitive diagnosis. Sampling can be done with a biopsy, fine-needle aspiration, or exfoliative cytology. This tissue sample is examined by a pathologist, who assigns a stage to the cancer. This process is called pathological staging.

Radiation or chemotherapy should not begin without proper clinical and pathological staging. Clinical staging can be accomplished by imaging studies, which may include the following:

• A chest x-ray evaluates the spread of cancer to bones or lungs.

• Computed tomography (CT) assesses the size, shape, and position of tumor and detects masses in lymph nodes, brain, or adrenal glands through a three-dimensional view.

• Magnetic resonance imaging (MRI) evaluates the spread of cancer to the brain or spinal cord.

• Positron emission tomography (PET) evaluates lymph and other metastatic involvement.

• A bone scan assesses for the presence of bone metastasis.

Laboratory work may include complete blood counts (CBCs), blood chemistries, and tumor markers (see Section 19.3).

If a diagnosis of cancer is made, the malignancy will need to be staged or categorized on the basis of severity of the disease and the results of the pathological staging tests. Staging guides the oncology practitioner in determining the prognosis and the treatment regimen for the patient.

The tumor, node, metastasis (TNM) staging system is the most commonly used tool for solid tumors. Tumors are scored numerically on the basis of the size of the tumor, the extent of lymph node involvement, and presence or absence of metastases. This score allows classification of tumors by stage, from 0 to IV, with stage IV denoting the presence of metastasis (e.g., most severe disease). A stage 0 tumor is called a carcinoma in situ, where the malignancy has not yet invaded the basement membrane of the epithelial surface.

Lymphoid tumors are staged differently and are beyond the scope of this review. Refer to Adams et al. (2002) for more information.

Treatment Principles and Goals

Treatment regimens are based on the type of cancer, stage, the age of the patient, and other prognostic factors (e.g., presence of a tumor marker, poor performance status, and ethnicity, among others).

Primary therapy is the initial and mainstay approach to treat cancer. It usually consists of removal of the tumor or debulking through surgery.

Neoadjuvant therapy is given prior to the primary therapy. The goal is to reduce the size of the tumor, thereby increasing the efficacy of the primary treatment. Examples include chemotherapy or radiation.

Adjuvant therapy is additional therapy given after the main treatment. The goal is to ensure that all residual disease has been eradicated.

The four main cancer treatments are surgery, radiation, chemotherapy, and biologic therapy. Most regimens are a combination of these modalities:

• Surgery alone is reserved for solid localized tumors, where the entire cancer can be resected. It may also be combined with other modalities in later stages of disease. It is not an option for patients with lymphoid-based disease (e.g., Hodgkin lymphoma).

• Radiation alone is also reserved for curing localized tumors because it treats a very focused area. It also can be combined with other treatments as neoadjuvant or adjuvant therapy to reduce disease-related symptoms or to reduce the incidence of disease recurrence.

• Chemotherapy is a means of systemic treatment, in contrast to the two types of local treatment just described. It can be used to treat the primary tumor as well as metastases. Chemotherapy is generally not administered to patients with local disease that can be fully resected.

• Biologic therapy is another systemic treatment and includes agents such as monoclonal antibodies, interferons, interleukins, and tumor vaccines. It is a relatively new type of treatment and acts by stimulating the host immune system.

The goals of cancer therapy are based on the type and stage of cancer, as well as on patient characteristics (e.g., an older patient with a short life expectancy may not be offered intense treatment that may impair quality of life). Goals may be as follows:

• Localized or regional disease (i.e., stages 0, I, II, and early III): Provide curative intent and inhibit recurrence of disease. Stage 0 diseases are often not treated, but monitored until clinically apparent.

• Advanced or metastasized disease (i.e., advanced stage III and all stage IV): Palliate symptoms, reduce tumor load, prolong survival, and increase quality of life.

Survival and response to treatment

In 2009, more than 1,500 people per day will die of a cancer-related cause, which accounts for one in four deaths. Survival depends on patient characteristics, type of disease, stage of disease, and treatment regimen. Older patients with more severe disease, a poor performance status, and faster-growing tumors have a poor prognosis.

Response to treatment modalities for solid tumors are classified as follows:

• Cure: 5 years of cancer-free survival for most tumor types

• Complete response: Absence of all neoplastic disease for a minimum of 1 month after cessation of treatment

• Partial response: ≥ 50% decrease in tumor size or other disease markers for a minimum of 1 month

• Stable disease: No change or no meeting of criteria for partial response or progression

• Progression: ≥ 25% increase in tumor size or new lesion

Response to treatment for hematologic cancers is measured by the elimination of abnormal cells, a decrease in tumor markers to normal, and the improved function of affected cells.

19-2. Drug Therapy

Chemotherapy

Chemotherapeutic agents have a very narrow therapeutic index and a toxic side-effect profile. They are generally more effective in combination because of synergism through biochemical interactions. It is important to choose drugs with different mechanisms of action, resistance, and toxicity profiles to get the full benefit of combination therapy.

Chemotherapy has the greatest effect on rapidly dividing cells, because most of the potent chemotherapy drugs act by damaging DNA. These agents are more active in different phases of the cell cycle. A therapeutic effect is seen on cancer cells, but adverse effects are also seen on human cells that rapidly divide (e.g., hair follicles, gastrointestinal (GI) tract, and blood cells). Agents can be phase specific or phase nonspecific. Nonspecific agents are effective in all phases.

Cell Cycle Phases

• G0 = resting phase: No cell division occurs, and cancer cells are generally not susceptible to chemotherapy. This lack of susceptibility is problematic for slow-growing tumors that exist primarily in this phase.

• G1 = postmitotic phase: Enzymes for DNA synthesis are manufactured, lasting 10-24 hours.

• S = DNA synthesis phase: DNA separation and replication occurs, lasting 10-20 hours.

• G2 = premitotic phase: Specialized proteins and RNA (ribonucleic acid) are made, lasting 2-10 hours.

• M = mitosis: Actual cell division occurs, lasting 30-60 minutes.

Drug Classes

There are numerous chemotherapy agents. Drugs are grouped by class. Refer to the corresponding table for each class of drugs.

Alkylating agents

Table 19-2 provides summary information about alkylating agents.

Mechanism of action

Alkylating agents cause covalent bond formation of drugs to nucleic acids and proteins, which results in the cross-linking of one or two DNA strands and inhibition of DNA replication. These agents are not phase specific. The most commonly used agents include cyclophosphamide, ifosfamide, carmustine, dacarbazine, and temozolomide.

Patient instructions and counseling

• All drugs are carcinogenic, teratogenic, and mutagenic.

• Medications may cause sterility.

• Let your dentist know you are on chemotherapy because of an increased risk of bleeding and infections.

• Hydration and mesna therapy are recommended for cyclophosphamide and ifosfamide.

• Let your doctor know if you have burning on urination.

Adverse drug events

The following adverse events may occur: myelosuppression, primarily leukopenia; mucosal ulceration; pulmonary fibrosis (carmustine) and interstitial pneumonitis; pyrexia and fatigue (bendamustine); alopecia; nausea and vomiting; amenorrhea and azoospermia; hemorrhagic cystitis with cyclophosphamide and ifosfamide; encephalopathy with ifosfamide; and seizures (polifeprosan and carmustine).

Drug interactions

Drugs with specific interactions of moderate to major severity include the following:

• Altretamine: Tricyclic antidepressants and monoamine oxidase inhibitors

• Bendamustine: Strong cytochrome P450 (CYP450) 1A2 inhibitors

• Busulfan: Itraconazole, phenytoin, and acetaminophen

• Carmustine: Cimetidine, ethyl alcohol, phenytoin, and amphotericin B

• Cyclophosphamide: Allopurinol, barbiturates, digoxin, phenytoin, and warfarin

• Ifosfamide: Allopurinol, phenytoin, and warfarin

• Streptozocin: Nephrotoxic agents

Monitoring parameters

Monitor pulmonary function tests, renal and hepatic tests, chest x-rays; CBC with differential (baseline and expected nadir prior to next cycle) and electrolytes, urinalysis for red blood count detection from hemorrhagic cystitis, signs of bleeding (bruising and melena), infection (sore throat and fever), and nausea or vomiting.

[Table 19-2. Alkylating Agents]

Antimetabolites: S-phase specific

See

Table 19-3 for general information about antimetabolites.

Mechanism of action

These agents are structural analogues of natural metabolites and act by falsely inserting themselves in place of a pyrimidine or purine ring, causing interference in nucleic acid synthesis. Phase-specific agents are most active in the S phase and in tumors with a high growth fraction. They are subdivided into three groups: folate, purine, and pyrimidine antagonists.

Patient instructions and counseling

• Avoid crowds and sick people.

• You may be asked to chew ice if receiving fluorouracil (5-FU) to reduce damage to the mucosal lining in your mouth.

• Contact your doctor if you have uncontrollable nausea or vomiting; excessive diarrhea; or pain, swelling, or tingling in palms of hands and soles of feet (hand-foot syndrome).

• Call your doctor if you feel dizzy or lightheaded or have trouble urinating (clofarabine).

• You should be receiving folic acid and vitamin B12 injections if you are receiving pemetrexed.

• Nelarabine may cause sleepiness and dizziness.

Adverse drug events

Adverse events include hand-foot syndrome, stomatitis (5-FU and capecitabine); severe diarrhea, GI mucosal damage, nausea, vomiting, fatigue, myelosuppression, alopecia, neurotoxicity (nelarabine, cytarabine, fludarabine, and methotrexate); rash, fever, and flu-like symptoms (gemcitabine); renal toxicity and mucositis (5-FU and methotrexate); conjunctivitis

[Table 19-3. Antimetabolites]

(cytarabine, especially in high doses); hemolytic uremic syndrome (gemcitabine); opportunistic infections (cladribine and fludarabine); and tumor lysis syndrome, systemic inflammatory response syndrome, or capillary leak (clofarabine).

Interactions

Drugs with specific interactions include the following:

• Capecitabine: Warfarin and phenytoin

• Cytarabine: Digoxin

• Fluorouracil: Warfarin

• Mercaptopurine: Warfarin and allopurinol

• Methotrexate: Nonsteroidal anti-inflammatory drugs (NSAIDs), amiodarone, amoxicillin, sulfasalazine, doxycycline, erythromycin, hydrochlorothiazide, mercaptopurine, omeprazole, phenytoin, and folic acid

• Pentostatin: Cyclophosphamide and fludarabine

Monitoring parameters

Note any complaints of mucositis or mouth soreness; monitor for neurotoxicity (e.g., ask the patient to write his or her name), CBC with differential prior to each dose of drug, and hepatic and renal function; and monitor for tingling or swelling of palms of hands and soles of feet, bruising or bleeding, and international normalized ratio (capecitabine). Monitor weight and question patient about diarrhea, jaundice, and hepatomegaly (mercaptopurine). Continuous intravenous (IV) fluids and allopurinol for prevention of tumor lysis syndrome should be administered to patients taking clofarabine, and those patients should also receive prophylactic corticosteroids for systemic inflammatory response syndrome and capillary leak. Pemetrexed toxicities are reduced by lowering plasma homocysteine levels with concomitant folic acid and vitamin B12. Dexamethasone should be given to prevent cutaneous reactions caused by pemetrexed.

Antitumor antibiotics

For additional information about antitumor antibiotics, consult

Table 19-4.

Mechanism of action

Anthracyclines block DNA and RNA transcription through the intercalation (insertion) of adjoining nucleic acid pairs in DNA, which results in DNA strand breakage. They also inhibit the topoisomerase II enzyme. Mitomycin is an alkylating-like agent that cross-links DNA. Dactinomycin blocks RNA synthesis. Bleomycin inhibits DNA synthesis in mitosis and G2 stages of growth. Bleomycin is the only cell cycle-specific agent.

Patient instructions and counseling

• Contact your doctor if you have fast, slow, or irregular heartbeats or breathing difficulties.

• Anthracyclines may cause a change of urine color or change the whites of eyes to a blue-green or orange-red.

• Bleomycin may cause a change in skin color or nail growth.

Adverse drug events

Events include severe nausea and vomiting, alopecia, and stomatitis. Anthracyclines may cause cardiac toxicity, acute or chronic (doxorubicin = daunorubicin > idarubicin > epirubicin > mitoxantrone). All anthracyclines have limits on cumulative lifetime dosing, are vesicants, and are associated with secondary acute myelogenous leukemia (AML); avoid in patients with a cardiac history. Myelosuppression risk exists with all agents, although mitomycin demonstrates a delayed

[Table 19-4. Antitumor Antibiotics]

effect. Dactinomycin may cause renal toxicity, leukopenia, and increased pigmentation of previously radiated skin. Bleomycin may cause pulmonary fibrosis and interstitial pneumonitis. Mitomycin may cause hemolytic uremic syndrome.

Drug interactions

Drugs with specific interactions include the following:

• Bleomycin: Phenytoin and digoxin

• Doxorubicin: Cisplatin, digoxin, paclitaxel, phenytoin, phenobarbital, trastuzumab, and zidovudine

• Epirubicin: Cimetidine and trastuzumab

• Idarubicin: Probenecid and trastuzumab

Monitoring parameters

Monitor hepatic and renal function, CBC with differential, and pulmonary function tests before and after treatment with bleomycin. Provide cardiac monitoring through left ventricular ejection fraction measurements for anthracyclines as well as monitoring of the cumulative lifetime dose, and be alert for extravasation and necrosis with anthracyclines. Adjust anthracycline dosing on the basis of elevated total bilirubin.

Pharmacokinetics

Anthracyclines are extensively bound in the tissue, have large volumes of distribution and long half-lives, and are excreted in the bile. Dosing adjustments are necessary in patients with hepatic impairment. Bleomycin is renally excreted and requires dosing adjustments in impaired patients.

Other factors

Lifetime doses of doxorubicin should not exceed 450-550 mg/m2, taking into account other anthracycline agents received. The lifetime maximum for epirubicin is 900 mg/m2; for idarubicin, it is 150 mg/m2.

Hormones and antagonists

Table 19-5 provides information about hormones and antagonists.

Mechanism of action

This diverse group of compounds acts on hormone-dependent tumors by inhibiting or decreasing the production of the disease-causing hormone.

Patient instructions and counseling

• Avoid use in pregnant women; several agents may cause weight gain and menstrual irregularities in women.

• Be aware of leg swelling or tenderness (e.g., signs of a deep vein thrombosis), breathing problems, and sweating.

• Transient muscle or bone pain, problems urinating, and spinal cord compression may occur initially in patients receiving luteinizing hormone-releasing hormone (LHRH) agonists.

• Take exemestane after meals.

Adverse drug events

Events include edema, menstrual disorders, hot flashes, transient muscle or bone pain, tumor flare, and transient increase in serum testosterone (LHRH agonists); thromboembolic events, gynecomastia, elevated liver enzymes, nausea and vomiting, diarrhea, erectile impotence, decreased libido, endometrial cancers with tamoxifen, bone loss (LHRH and aromatase inhibitors); and risk of ventricular arrhythmias and QT prolongation.

Interactions

Drugs with specific interactions include the following:

• Aminoglutethimide: Dexamethasone, warfarin, tamoxifen, and theophylline

• Bicalutamide: Warfarin

• Degarelix: Amiodarone, procainamide, quinidine, and sotalol

• Fluoxymesterone: Cyclosporine, anticoagulants, and valerian

• Flutamide: Warfarin

• Medroxyprogesterone acetate: Aminoglutethimide and rifampin

• Megestrol: Dofetilide contraindication

• Nilutamide: Alcohol

• Tamoxifen: Anticoagulants and cyclophosphamide

• Toremifene: CYP450 3A4 inducers (carbamazepine and phenytoin)

Monitoring parameters

Check white blood counts (WBCs) with differential, platelets, liver function tests, thyroid function, and serum creatinine regularly. Note any weight changes, abnormal vaginal bleeding, body or bone pain, galactorrhea, or decreased libido. Monitor for embolic disorders and uterine cancer (in females). Check prostate-specific antigen (PSA) and testosterone levels in males. Monitor bone mineral density for LHRH agonist and aromatase inhibitors.

Pharmacokinetics

The majority of agents are available orally with longer half-lives, allowing once-daily dosing.

[Table 19-5. Hormones and Antagonists]

Other factors

Agents are often contraindicated if the patient has more than one hormone-dependent tumor. With the exception of tamoxifen, third generation aromatase inhibitors, and LHRH agonists, the majority of agents are not indicated for first-line therapy.

Plant alkaloids

See

Table 19-6 for information about plant alkaloids.

Mechanism of action

These agents inhibit the replication of cancerous cells. Taxanes and vincas interfere with microtubule assembly in the M phase. Camptothecins and epipodophyllotoxins inhibit topoisomerase I and II enzymes, respectively, causing DNA strand breaks. Topoisomerase I and II affect G2 and S phases, respectively.

Patient instructions and counseling

• Contact doctor for uncontrollable diarrhea (irinotecan), nausea or vomiting, or signs and symptoms of an infection.

• Patients should receive prophylaxis for emesis and pretreatment for anaphylaxis or peripheral edema (taxanes).

• Patients should receive a prescription for loperamide for delayed diarrhea with irinotecan therapy.

Adverse drug events

Adverse events include myelosuppression, mucositis, nausea and vomiting, alopecia, edema, hand-foot syndrome (docetaxel); hypotension or hypersensitivity on administration (paclitaxel); neurotoxicity (vincristine); peripheral neuropathy and myalgia or arthralgia (ixabepilone and paclitaxel); diarrhea, headache, and secondary malignancies (topoisomerase II inhibitors); and syndrome of inappropriate antidiuretic hormone secretion (SIADH) (vinca alkaloids)

Interactions

Drugs with specific interactions include the following:

• Docetaxel: CYP450 3A4 inducers and inhibitors

• Etoposide: Cyclosporine, St. John's wort, and warfarin

[Table 19-6. Plant Alkaloids]

• Irinotecan: St. John's wort

• Ixabepilone: CYP450 3A4 inducers and inhibitors

• Paclitaxel: CYP450 3A4 inducers and inhibitors

• Teniposide: CYP450 3A4 inducers and inhibitors

• Vinblastine: Phenytoin, erythromycin, mitomycin, and zidovudine

• Vinca alkaloids: CYP450 3A4 inhibitors; itraconazole, and voriconazole

• Vincristine: Phenytoin, l-asparaginase, carbamazepine, digoxin, filgrastim, nifedipine, and zidovudine

Monitoring parameters

Monitor WBCs with differential for all agents; peripheral neuropathy, liver and renal function, painful mouth sores, and blood pressure (taxanes and epipodophyllotoxins); acute and late-onset diarrhea or dyspnea on exertion (irinotecan); bilirubin elevations (taxanes and camptothecins); fluid retention (docetaxel); and neuropathy, shortness of breath, bronchospasm, and SIADH (vincas).

Pharmacokinetics

Taxanes and epipodophyllotoxins are extensively bound to plasma and tissues.

Other factors

Drug resistance may occur through p-glycoprotein pumps for all agents. Topotecan needs dose adjustments for patients with a creatinine clearance < 40 mL/min. Vincas are vesicants and need close monitoring for extravasation. Vincristine should not be administered intrathecally. In adult patients, vincristine doses are often capped at 2 mg.

Dose adjustments may be needed for patients with liver impairment.

Biologic response modifiers and monoclonal antibodies

Table 19-7 provides information about biologic response modifiers and monoclonal antibodies.

[Table 19-7. Biologic Response Modifiers and Monoclonal Antibodies]

Mechanism of action

Biologic response modifiers activate the body's immune-mediated host defense mechanisms to malignant cells. In contrast to immunotherapy, these agents have direct biological effects on malignancies. Monoclonal antibodies bind to specific antigens and kill malignant cells through the activation of apoptosis, an antibody-mediated toxicity, or complement-mediated lysis.

Patient instructions and counseling

• Let your doctor know if you have severe fatigue, trouble breathing, or irregular heart rhythms.

• Chills, fever, depression, and flu-like symptoms are common.

• Monoclonal antibodies can cause infusion-related reactions such as fever and chills.

• If you receive bevacizumab, you should have your blood pressure checked regularly and have tests that check for protein in your urine.

• You should wear sunscreen and avoid excessive sunlight if you are receiving cetuximab.

• You should receive medication for your thyroid if you are going to receive tositumomab.

• For both men and women, do not try to conceive until 12 months after finishing therapy.

• With thalidomide and lenalidomide, do not get pregnant. Two forms of birth control must be used, both by women and by men on the drug who have sexual contact with women of childbearing age.

Adverse drug events

Events include hypotension and hypersensitivity on infusion; cardiac, pulmonary, and renal impairment; and mental status changes (e.g., depression), fever, chills, nausea, and musculoskeletal pain with all agents. Other events include tumor lysis syndrome (rituximab); bleeding, hemorrhage, hypertension, proteinuria, and skin rash (bevacizumab); cutaneous and severe infusion reactions and interstitial lung disease (cetuximab); and hypothyroidism (tositumomab). Avoid use in patients with autoimmune disorders.

Additional events include neurotoxicity (thalidomide), neutropenia (thalidomide and lenalidomide), and deep-vein thrombosis and pulmonary embolism (thalidomide and lenalidomide).

Interactions

Drugs with specific drug interactions include the following:

• Aldesleukin: Glucocorticoids, NSAIDs, and antihypertensives

• Ibritumomab: Antiplatelets and anticoagulants

• Interferon-alfa 2b: Zidovudine, theophylline, phenytoin, and phenobarbital

• Tositumomab: Antiplatelets and anticoagulants

• Trastuzumab: Anthracyclines, cyclophosphamide, and warfarin

Monitoring parameters

Monitor baseline and follow-up pulmonary, cardiac, and renal function tests. Check CBCs with differential, liver function tests, thyroid-stimulating hormone, electrolytes, and glucose regularly. Premedicate with acetaminophen and diphenhydramine for monoclonal antibodies. Observe blood pressure during infusion (hypotension concerns) for all agents. Perform blood pressure monitoring (hypertensive concerns) and urine dipstick analysis (bevacizumab). Monitor for vital signs, itching, and swelling. Check for trouble breathing (cetuximab and ibritumomab).

Other factors

Ensure that the correct form of interferon alfa is being used (four forms). Do not administer gemtuzumab and alemtuzumab as an IV push or bolus.

Miscellaneous Agents

Miscellaneous agents are described in

Table 19-8.

Platinum compounds

These compounds are alklyating-like agents that cause the inhibition of DNA synthesis. They include cisplatin, carboplatin, and oxaliplatin. Adverse effects include nephrotoxicity, peripheral neurotoxicity, myelosuppression, ototoxicity, nausea, and vomiting.

Cisplatin needs hydration therapy and premedications. It interacts with doxorubicin, rituximab, tacrolimus, topotecan, and aminoglycosides.

Carboplatin needs monitoring for thrombocytopenia. It interacts with aminoglycosides.

Oxaliplatin has unique neurotoxicities (e.g., bronchial spasms).

Sorafenib

Sorafenib inhibits multiple tyrosine kinases and is used for treatment of advanced renal cell cancer. Take tablets on an empty stomach. Sorafenib causes diarrhea, fatigue, rash, hand-foot syndrome, hypertension, nausea and vomiting, neutropenia, and alopecia. It can decrease doxorubicin and irinotecan levels.

Sunitinib

Sunitinib inhibits multiple tyrosine kinases and is used for treatment of advanced renal cell cancer and GI

[Table 19-8. Miscellaneous Agents]

stromal tumors. Take it with or without food. It causes neutropenia, rash changes in skin color, fatigue, myalgia, headaches, hypertension, nausea and vomiting, diarrhea, and increased liver enzymes. It is extensively metabolized by CYP3A4; CYP3A4 inhibitors may increase levels, and CYP3A4 inducers may decrease levels. Ketoconazole increases levels, and rifampin reduces levels.

Dasatinib

Dasatinib specifically targets BCR-ABL mutations (including those resistant to imatinib), thereby inhibiting leukemic cell growth. It is used for treatment of chronic myelogenous leukemia (CML) and pH+ acute lymphocytic leukemia (ALL). It causes rash neutropenia, thrombocytopenia, edema, diarrhea, nausea and vomiting, weight changes, arthralgia, myalgia, cough, shortness of breath, infection, electrolyte changes, and arrhythmias. Significant drug interactions occur with CYP3A4 inhibitors; avoid concurrent use or reduce dose. Avoid acid reduction therapies because they will reduce absorption. Avoid medications that prolong QT interval.

Lapatinib

Lapatinib inhibits multiple tyrosine kinases and is used in combination with capecitabine to treat human epidermal growth factor receptor-2 (HER2) positive breast cancer. Common adverse effects include fatigue, diarrhea, nausea, vomiting, myelosuppression, increased liver enzymes, and palmar-plantar erythrodysesthesia. Significant drug interactions occur with strong CYP450 3A4 inhibitors and inducers; avoid concurrent use or reduce dose. These agents should be taken by mouth, on an empty stomach, 1 hour prior to or 2 hours after a meal.

Nilotinib

Nilotinib selectively inhibits BCR-ABL kinase and is used for the treatment of pH+ CML. Adverse effects include headache, fatigue, rash, pruritus, constipation, nausea, vomiting, and diarrhea. Significant drug interactions occur with strong CYP450 3A4 inhibitors and inducers; avoid concurrent use or reduce dose. Capsules should be taken by mouth, on an empty stomach, and swallowed whole; do not crush or open.

Asparaginase

Asparaginase removes exogenous asparagines from leukemic cells that are required for their survival. Intradermal skin testing is needed because of severe anaphylactic reactions. Adverse effects include myelosuppression, hyperuricemia, hyperglycemia, and renal problems. Drug interactions occur with methotrexate, prednisolone, prednisone, and vincristine.

Hydroxyurea

Hydroxyurea inhibits DNA synthesis without interfering with RNA and protein synthesis. Adverse effects include myelosuppression (leukopenia), development of secondary leukemias, nausea, vomiting, diarrhea, constipation, mucositis, and rare but fatal hepatotoxicity and pancreatitis. Drug interactions occur with didanosine and stavudine.

Imatinib mesylate

Imatinib mesylate is a selective inhibitor of the Philadelphia chromosome (biomarker in CML). It causes hepatotoxicity, fluid retention (pleural effusions and weight gain), neutropenia, GI effects, muscle cramps, nausea, and vomiting. Drug interactions occur with CYP450 3A4 substrates (cyclosporine, simvastatin, erythromycin, and itraconazole) and CYP450 2C9 substrates (warfarin).

Erlotinib

Erlotinib is an HER1 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. For oral therapy, take 1 hour before or 2 hours after meals. Erlotinib causes rash, diarrhea, anorexia, stomatitis, and interstitial lung disease. Drug interactions occur with CYP450 3A4 inducers and inhibitors. Monitor hepatic function.

Gefitinib

Gefitinib is an EGFR tyrosine kinase inhibitor and a third-line agent for non-small cell lung cancer (NSCLC). It causes diarrhea, rash, acne, and dry skin. Drug interactions occur with CYP450 3A4 inducers and inhibitors and with warfarin.

Bortezomib

Bortezomib inhibits the 26S proteasome and stabilizes regulatory proteins causing apoptosis and disrupting cell proliferation. It causes nausea, vomiting, thrombocytopenia, neuropathy, hypotension, and diarrhea.

Temsirolimus

Temsirolimus inhibits the mammalian target of rapamycin (MTOR) and is used for the treatment of renal cell carcinoma. Adverse effects include myelosuppression, anorexia, rash, mucositis, edema, hyperglycemia, dyslipidemia, and nausea. Drug interactions occur with angiotensin-converting enzyme inhibitors and strong CYP450 3A4 inhibitors and inducers.

Common Toxicities and Treatments

Common toxicities of chemotherapeutic agents are outlined in

Table 19-9. They can be classified as acute, subacute, chronic, cumulative, or chronic and cumulative. Rapidly dividing cells, including mucous membranes, hair, skin, GI tract, and bone marrow, are the most common acute toxicities. Examples of delayed or cumulative toxicities include nephrotoxicity, neurotoxicity, cardiomyopathy, pulmonary fibrosis, and secondary malignancies.

The prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) constitute an important area in which pharmacists may play a role in drug selection in oncology patients. The selection of antiemetic agents should be based primarily on the emetogenic potential of the drug regimen. Other factors that increase the risk of CINV include sex (female), young age, prior chemotherapy exposure, lack of chronic alcohol use, combination chemotherapy, high dosage and numerous cycles, and short infusion times. It is important that patients also receive prescriptions to prevent delayed CINV.

Table 19-10 summarizes the pertinent antiemetic drugs used in the prophylactic setting.

[Table 19-9. Common Toxicities of Chemotherapeutic Agents]

For highly to moderately emetogenic drug regimens, dexamethasone and 5-HT3 receptor antagonists are recommended—at a minimum—for the prevention of acute CINV. Aprepitant should also be considered, especially for highly emetogenic regimens.

For low to minimally emetogenic drug regimens, dexamethasone and a phenothiazine are recommended.

For prevention of delayed CINV (> 24 hours after administration of highly emetogenic and some moderately emetogenic chemotherapy), aprepitant and dexamethasone are recommended.

All patients receiving agents with emetogenic potential should receive prophylactic therapy for CINV, with rescue medication readily available.

Miscellaneous Commonalities across Chemotherapy Agents

• Patients should not receive live and rotavirus vaccines during chemotherapy because of immune suppression.

• The majority of agents are teratogenic and mutagenic.

[Table 19-10. Pharmacologic Management for the Prevention of Acute Chemotherapy-Induced Nausea and Vomiting]

• Patients should avoid becoming pregnant or breast-feeding during and immediately after chemotherapy.

• Patients should have laboratory studies done on a regular basis to check for common toxicities, such as myelosuppression, renal and hepatic impairment, and electrolyte disturbances.

19-3. Nondrug Therapy

As mentioned previously, cancer treatment is generally a combination of modalities. Chemotherapy is an important component, because most patients present with advanced disease on diagnosis. Surgery plays a role in resecting primary tumors or metastases. It can

[

Table 19-11. American Cancer Society Screening Recommendations]

also be used for diagnostic purposes to biopsy tumors or for other exploratory purposes. Radiation is used to shrink primary tumors in local disease or metastases. It can be used both in neoadjuvant therapy to downsize tumors and in adjuvant therapy to eradicate residual disease.

Screening is also an important part of cancer therapy, because it can allow the detection of disease in very early stages, when the survival rates are much higher. Table 19-11 refers to American Cancer Society screening recommendations for patients at average risk of developing cancer.

Tests can also be performed to screen and monitor tumor markers. They are found in the plasma, serum, or other body fluids and may be used to identify neoplastic growth. These markers are often not sensitive enough to diagnose cancer and may produce false positive results (i.e., falsely identify people with a disease that they do not have). However, they are helpful in identifying the recurrence of advanced disease in patients who had elevated levels on diagnosis.

Table 19-12 lists some commonly used tumor markers.

[Table 19-12. Common Tumor Markers and Associated Cancers]

19-4. Key Points

• Oncology includes more than 100 diverse diseases that share properties of abnormal and detrimental cell growth.

• Diseases are classified on the basis of the tissue in which they originate (e.g., breast cancer metastasized to the brain is classified as breast cancer).

• Signs and symptoms of cancer do not follow a specific pattern. A health care provider should evaluate any unusual or persistent change in body appearance or function.

• Before a diagnosis of cancer can be made and systemic treatment can begin, a positive biopsy or blood examination must confirm the presence of the disease.

• Further imaging and laboratory work-up should be done to evaluate the extent of the disease (i.e., determine the stage of disease).

• Cancer therapy must be individualized to each patient on the basis of the type and severity of disease, patient characteristics, and patient and family preferences.

• Surgery, radiation, chemotherapy, and biologic therapy are all cancer treatment modalities. They are often used in combination.

• Pharmacists can affect patients' chemotherapy and biologic therapy by counseling the patients and educating health care providers on details of the individual drug regimens.

• Chemotherapy is often used in combinations to take advantage of different mechanisms of action, prevent resistance, and minimize toxicities.

• Most chemotherapy is aimed at rapidly proliferating cancerous cells. However, many chemotherapy-related side effects occur in normal highly proliferative cells of the body, such as hair follicles, the gastrointestinal tract lining, and blood cells.

• Patients should be aware of expected toxicities of chemotherapy, which include alopecia, diarrhea, nausea and vomiting, infertility, myelosuppression, neurotoxicity, nephrotoxicity, hepatotoxicity, stomatitis, and pulmonary toxicity.

• The importance of laboratory studies and follow-up appointments to treatment should be stressed to the patient.

• All prophylactic and post-treatment medications for chemotherapy-related complications should be made available to the patient. Counsel the patient to keep a diary of events that occur prior to and after treatments. Use this record to make interventions and monitor the patient's quality of life.

• All pharmacists should be aware of the accepted cancer screening recommendations and should discuss these with patients. Many diseases can be cured if they are caught early enough.

• It is the pharmacist's responsibility to ensure that the patient and family are adequately educated to participate in making decisions about their care.

19-5. Questions

Use Patient Profile 1 to answer questions 1-5.

 

Patient name:

Tina Tiny

Age:

33

Sex:

Female

Diagnosis:

1. Diagnosis on 12/03 of metastatic breast cancer

 

2. Mastectomy to right

 

breast on 12/15/03

 

3. Weight loss of 20 lbs

 

4. Allergies

Address:

234 Small Street

Height:

5´8″

Weight:

150 lbs

Allergies:

Sulfa, penicillin

Pharmacist notes:

Date

Note

01/04

Patient complained of soreness after mastectomy and swelling of right arm.

03/04

Patient did not pick up birth control last month (2/04).

03/04

Patient is receiving Zoladex 3.6 mg SC q28d at oncology clinic. Received dose today.

 

Medication record:

Date

Rx no.

Physician

Drug and strength

Quantity

Sig

Refills

12/03

12345

Buford

Percocet 5/325

30

1-2 q4h prn

0

03/04

12347

Buford

Tamoxifen 20 mg

30

1 po qd

2

03/04

12349

Buford

Megace 40 mg/mL

80 mg/d

2

03/04

12350

Charles

Celebrex 10 mg

30

1 po qd

2

1.

Which of the following agents that Ms. Tiny is taking can be used to treat breast and prostate cancer?

I. Zoladex

II. Tamoxifen

III. Celebrex

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

2.

When Ms. Tiny presents the tamoxifen prescription, you notice that the directions are missing. You call the doctor to clarify what the instructions are for this patient. Which of the following is a correct choice?

A. 10 mL po qd

B. 20 mL po qd

C. 40 mg po bid

D. 20 mg po qd

E. 5 mg po bid

 

3.

Ms. Tiny presents to your pharmacy with complaints of lower leg calf pain that is tender to the touch and red. You suspect a deep-vein thrombosis. Which of the following agents is most likely to be associated with this condition?

I. Megace

II. Goserelin

III. Tamoxifen

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

4.

Ms. Tiny calls you 2 days after her 03/04 visit to your pharmacy. She has been feeling a lot of bone pain and describes an "achy, creaky feeling all over." She is worried that her cancer has spread to her bones. What advice can you give her?

I. She should call her oncology caretaker and be formally evaluated.

II. This could be a side effect of her Zoladex therapy, and the pain should subside.

III. This could be a side effect of her Celebrex therapy, and the pain should subside.

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

5.

Ms. Tiny's mother (age 59) is worried that she will develop breast cancer like her daughter. Which of the following is not an appropriate initial screening test for breast cancer?

A. Monthly breast self-examination

B. Clinical breast examination

C. Mammography

D. Biopsy

E. Mammography and clinical breast examination

 

6.

Which of the following classes of agents is best known for causing infusion-related reactions, such as fever and chills?

I. Monoclonal antibodies

II. Alkylating agents

III. Vinca alkaloids

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

7.

Your patient has just received 5-FU and irinotecan for the treatment of colorectal cancer. Before he leaves the clinic, you ensure that he has a prescription to prevent or treat which of the following side effects from irinotecan?

A. Nausea with Aloxi

B. Diarrhea with loperamide

C. Headache with aspirin

D. Delayed allergic reaction with epinephrine

E. Change in urine color: no treatment available

 

8.

Which of the following drugs is an oral prodrug of 5-FU?

A. Fluorouracil

B. Xeloda

C. Fludara

D. Cytoxan

E. Alkeran

 

9.

An elderly male patient comes to your pharmacy and is worried that he might have prostate cancer. He just had some laboratory studies done, and his doctor told him that some level was abnormal, indicating potential prostate cancer. Which lab test might he be talking about?

I. PSA

II. Cortisol

III. ESR

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

10.

Stomatitis is the clinical term for which of the following chemotherapy-related adverse effects?

I. Nausea and projectile vomiting

II. Obstruction of the lower esophageal sphincter

III. Inflammation of the mucosal lining of the mouth

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

11.

Which of the following does not describe characteristics of most chemotherapy agents?

A. They have a wide therapeutic index.

B. They interfere with DNA synthesis and replication.

C. They are more effective in combination.

D. Acute adverse effects occur primarily in rapidly dividing normal cells.

E. They have both phase-specific and non-phase-specific actions

 

Use Patient Profile 2 to answer questions 12-17.

 

Patient name:

Cassimer Migash

Age:

60

Sex:

Male

Diagnosis:

1. Diagnosis on 02/04 of metastatic non-small cell lung cancer

 

2. Chronic obstructive pulmonary disease

 

3. Asthma

Address:

579 Hunter's Ridge

Height:

180 cm

Weight:

200 lbs

Allergies:

NKDA

Lab and diagnostic tests:

Date

Test

05/04

WBC: 2,500/mcL

05/04

RBC: 2.8 × 106/mm3

05/04

PLT: 100 × 103/mcL

05/04

Theophylline: 10 mcg/mL

05/04

Hgb: 9 g/dL

05/04

Hct: 30%

 

Medication record:

Date

Route

Drug

Sig

04/04

IV

Paclitaxel 175 mg/m2

175 mg/m2over 3 h q 3 wk

04/04

IV

Carboplatin AUC 6

AUC 6 over 2 h q 3 wk

04/04

po

Theophylline SR 400 mg

1 tab po bid

04/04

INH

Albuterol inhaler

2 puffs prn

04/04

INH

Cromolyn inhaler

1 puff qid

04/04

INH

Beclomethasone inhaler

2 puffs qid

04/04

po

Dexamethasone 20 mg

1 tab 12 h and 6 h prior to chemo

04/03

IV

Diphenhydramine 50 mg

Infuse 30 min and 60 min prior to chemo

04/03

IV

Cimetidine 300 mg

Infuse 30 min and 60 min prior to chemo

12.

A nurse would like to know if she can administer the diphenhydramine and the cimetidine to Mr. Migash in the same IV line simultaneously. Which of the following resources will provide you with this information?

I. Wolters Kluwer Health's Facts & Comparisons

II. Trissel's Handbook on Injectable Drugs

III. Micromedex

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

13.

Which of the following agents being taken by Mr. Migash requires the premedication regimen of dexamethasone, diphenhydramine, and ranitidine or cimetidine to prevent an anaphylactic reaction?

I. Taxotere

II. Paraplatin

III. Taxol

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

14.

On the basis of the patient's weight and height, you calculate Mr. Migash's body surface area to be 2.1 m2. Paclitaxel is supplied as 6 mg/mL in 5 mL, 16.7 mL, and 50 mL vials. Your pharmacy has all quantities available. What is the best way to correctly dose this patient?

A. One 50 mL vial and one 16.7 mL vial

B. One 50 mL vial and one 5 mL vial

C. Two 16.7 mL vials

D. Two 16.7 mL vials and one 5 mL vial

E. Four 16.7 mL vials

 

15.

You are concerned that Mr. Migash will develop nausea and vomiting from his chemotherapy regimen. Which of the following regimens would be suitable to prevent acute CINV?

A. Dexamethasone, granisetron, and aprepitant

B. Granisetron and prochlorperazine

C. Metoclopramide, dexamethasone, and aprepitant

D. Palonosetron and granisetron

E. Lorazepam and droperidol

 

16.

On the basis of the patient's laboratory values, which of the following adverse reactions appear to have occurred as a likely result of the chemotherapy?

I. Thrombocytopenia

II. Leukopenia

III. Anemia

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

17.

The goal of Mr. Migash's treatment regimen is

I. to cure his disease.

II. to palliate his disease-related symptoms.

III. to increase his quality of life.

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III

 

18.

Doxorubicin is an antineoplastic agent that

A. is not related to epirubicin and daunorubicin.

B. interacts with the microtubules of cells during mitosis.

C. has an oral dosage form commercially available.

D. causes cumulative cardiac toxicity.

E. can also be used to treat tuberculosis.

 

19.

Which of the following agents is used in cancer regimens but is not considered an antineoplastic agent?

A. Methotrexate

B. Leucovorin

C. Doxorubicin

D. Cyclophosphamide

E. Gemcitabine

 

20.

Methotrexate (Rheumatrex) is not available as which of the following dosage forms?

A. An intravenous injection

B. An oral tablet or capsule

C. An intrathecal injection

D. An ointment

E. An intramuscular injection

 

19-6. Answers

1.

A. Zoladex (goserelin) is an LHRH agonist that can be used to treat both breast and prostate cancer. LHRH agonists are approved by the U.S. Food and Drug Administration (FDA) for premenopausal women because they inhibit estrogen production from the ovaries.

 

2.

D. The FDA-approved dose for breast cancer therapy is 20 mg po qd. The drug is not available in a liquid form.

 

3.

E. All three agents are hormonal products and are associated with thromboembolic side effects. It is important that patients on these products are aware of the signs and symptoms of deep-vein thrombosis.

 

4.

C. Although the bone pain is most likely a side effect of her Zoladex therapy, Ms. Tiny should notify her oncology practitioner so he or she can document this side effect. If other factors point to metastatic disease, she may need additional evaluation.

 

5.

D. Biopsies should never be performed as initial screening tests. However, if results from the mammography and other tests point to disease, a biopsy is needed to make a diagnosis. There is some debate about the usefulness of clinical breast examinations for women who are reluctant to perform breast self-examinations; however, clinical breast examinations should be offered.

 

6.

A. Monoclonal antibodies are commonly associated with infusion-related reactions. Patients should receive premedication, such as acetaminophen, to prevent this.

 

7.

B. Diarrhea is a dose-limiting toxicity of irinotecan. Late-onset diarrhea can be life threatening. All patients should receive a prescription for loperamide to treat delayed-onset diarrhea. Patients should be instructed to take 2 mg po q2h while awake and 4 mg po q4h during the night until the diarrhea has stopped for at least 12 hours. Acute-onset diarrhea can be treated with atropine.

 

8.

B. Xeloda (generic name capecitabine) is an oral prodrug of 5-FU. Fluorouracil is another name for 5-FU. Fludara is the brand name for fludarabine and is used to treat chronic lymphocytic leukemia and non-Hodgkin lymphoma intravenously. Cytoxan is the brand name for cyclophosphamide and is available in IV and po dosage forms. Alkeran is the brand name for melphalan and is also available in IV and po dosage forms.

 

9.

A. PSA (prostate-specific antigen) is a lab test that is commonly done in men over age 40. It should be performed annually in men over age 50 to check for prostate cancer.

 

10.

B.Stomatitis is used to describe an irritation or ulceration of the mucosal lining. This side effect is common with fluorouracil and methotrexate. Having the patient hold ice chips in his or her mouth during treatment can prevent it. The cold is thought to cause vasoconstriction of the lining and prevent damage.

 

11.

A. Chemotherapy agents have a very narrow therapeutic index. This is one of the main reasons these drugs have so many toxic effects. They can be phase specific or non-phase-specific drugs and can cause many adverse reactions to normal cells that undergo rapid proliferation.

 

12.

D. Both Trissel's Handbook on Injectable Drugs and the Micromedex IV compatibility tool can be used to assess whether diphenhydramine and cimetidine are compatible.

 

13.

B. Taxol is the brand name of paclitaxel. This agent has been shown to cause hypersensitivity reactions in patients. It is unclear if these reactions are due to the drug itself or the drug's vehicle (Cremophor). All patients receiving paclitaxel should receive a premedication regimen of dexamethasone, diphenhydramine, and ranitidine or cimetidine. Taxotere is the brand name of docetaxel. This agent also requires premedications with a minimum of a corticosteroid. However, this regimen is given to prevent peripheral edema, not an anaphylactic reaction.

 

14.

A. The patient requires 367.5 mg of drug. Both choice A and choice E will provide 400 mg of drug; however, using one large vial and one medium vial is more economical than using four medium vials.

 

15.

A. This patient's regimen contains carboplatin and paclitaxel. Together these agents have a high likelihood of causing acute (and delayed) CINV. The patient should receive a corticosteroid, a 5-HT3 antagonist, and a neurokinin-1 inhibitor, which makes choice B incorrect because it contains a 5-HT3 antagonist and a dopamine antagonist. Aprepitant is approved in combination with a corticosteroid and a 5-HT3 antagonist, which makes choice C incorrect because it adds a corticosteroid and a dopamine antagonist to the aprepitant. Choice D contains two 5-HT3 antagonists. Therapy should include more than one class of agent. Choice E agents are not efficacious in moderate to severe CINV.

 

16.

E. Myelosuppression is a common adverse reaction to most chemotherapy agents. Both paclitaxel and carboplatin can cause anemia, thrombocytopenia, and leukopenia. It is very important to monitor blood levels in these patients. If myelosuppression is too severe, the length of time between chemotherapy cycles may be increased so that all or some of the blood cells can return to normal levels.

 

17.

D. Mr. Migash has metastatic disease. When a solid tumor is diagnosed as stage IV, this finding is representative of the fact that the disease is incurable. The treatment goals for these patients include relieving any disease-related symptoms, minimizing toxicity from treatments, and increasing the patient's quality of life through treatment or supportive care measures.

 

18.

D. Doxorubicin is an antitumor antibiotic related to epirubicin and daunorubicin. These agents act by binding tightly to DNA through intercalation and by inhibiting the topoisomerase II enzyme. Doxorubicin does have a liposomal IV product, but it is not available orally. All anthracyclines are associated with cardiac toxicity and have cumulative dosing limits to prevent this.

 

19.

B. Leucovorin is a reduced folate agent that is used in combination with 5-FU to potentiate the therapeutic effects of 5-FU and as a rescue treatment for high-dose methotrexate.

 

20.

D. Methotrexate is not commercially available for topical use. It is available in all of the other dosage forms.

 

19-7. References

Adams VR, Yee GC. Lymphomas. In: Dipiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York: McGraw-Hill; 2002:2331-56.

American Cancer Society. Cancer facts & figures 2009. Available at: www.cancer.org.

Balmer CM, Valley AW. Cancer treatment and chemotherapy. In: Dipiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York: McGraw-Hill; 2002: 2175-222.

Chabner BA, Amrain PC, Druker B, et al. Antineoplastic agents. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill; 2006:1315-404.

DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practices of Oncology. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2008.

Dorr RT, Fritz WL. Cancer Chemotherapy Handbook. New York: Elsevier; 1980.

Medina PJ, Fausel C. Cancer treatment and chemotherapy. In: Dipiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 7th ed. New York: McGraw-Hill; 2008:2085-120.

Mueller BA, Schumock GT, Bertch KE, et al., eds. Pharmacotherapy Self-Assessment Program. 4th ed. Book 10, Hematology/oncology. Lenexa, Kans.: American College of Clinical Pharmacy; 2002.

National Comprehensive Cancer Network. NCCN clinical practice guidelines—Antiemesis. Ver. 3. 2009. Available at: www.nccn.org.