chapter 45 antineoplastic drugs part 1: cancer overview and cell cycle–specific drugs copyright ©...

Chapter 45

Antineoplastic Drugs Part 1:Cancer Overview and Cell

Cycle–Specific Drugs

Cellular transformation Uncontrolled and rapid cellular growth Invasion into surrounding tissue Metastasis to other tissues or organs

Cancer

Cancerous cells do not have: Growth control mechanisms Positive physiologic function

Cancer cells either: Grow and invade adjacent tissues, or Break away from original tumor mass and travel by

means of blood or lymphatic system to distant sites

Cancer (cont’d)

Primary lesion Original site of growth

Metastasis Uncontrolled cell growth Secondary lesion, in a new and remote part of the

body Neoplasm (“new tissue”)

Mass of new cells; tumor Tumor

Benign Malignant (cancer)

Cancer (cont’d)

Carcinomas Sarcomas Lymphomas and leukemias

Also known as circulating tumors or hematologic malignancies

Cancer: Tissues of Origin

Various group of symptoms that cannot be directly attributed to the spread of a cancerous tumor

May be the first sign of malignancy Cachexia (most common) Fatigue, fever, weight loss Others

Paraneoplastic Syndromes

Age- and sex-related differences Genetic factors Ethnic factors Oncogenic viruses Occupational and environmental carcinogens Radiation Immunologic factors

Etiology of Cancer

G0: resting phase

G1: first gap phase S: synthesis phase G2: second gap phase M: mitosis phase (cell reproduction)

Cell Growth Cycle

Pharmacologic treatment of cancer Antineoplastic drugs Divided into two groups based on where in the

cellular life cycle they work Cell cycle–nonspecific (CCNS) Cell cycle–specific (CCS)

Some drugs have characteristics of both

Chemotherapy

Cell cycle–specific drugs Drugs that are cytotoxic during a specific cell-cycle

phase Used to treat a variety of solid and/or circulating

tumors• Antimetabolites

• Mitotic inhibitors

• Alkaloid topoisomerase II inhibitors

• Topoisomerase I inhibitors

• Antineoplastic enzymes

Cancer Drugs:Antineoplastic Medications

Cell cycle–nonspecific drugs Cytotoxic during any cell-cycle stage

Cancer Drugs:Antineoplastic Medications (cont’d)

Miscellaneous cell cycle–specific drugs Miscellaneous antineoplastics (cell-cycle

specificity unclear) Hormonal agents Radioactive antineoplastics

Cancer Drugs:Antineoplastic Medications (cont’d)

Drugs have a narrow therapeutic index Combination of drugs is usually more effective

than single-drug therapy Drug resistance Nearly all drugs cause adverse effects Dose-limiting adverse effects

Chemotherapy (cont’d)

Harmful to all rapidly growing cells Harmful cancer cells Healthy, normal human cells

• Hair follicles

• GI tract cells

• Bone marrow cells

Chemotherapy (cont’d)

Dose-limiting adverse effects GI tract and bone marrow

Alopecia Emetic potential Myelosuppression

Bone marrow suppression (BMS) Bone marrow depression (BMD)

Nadir Extravasation Targeted drug therapy

Chemotherapy Terms

Folate (folic acid) antagonists methotrexate (MTX), pemetrexed, palatrexate

Purine antagonists fludarabine (F-AMP),mercaptopurine (6-MP),

thioguanine (6-TG), cladribine, pentostatin Pyrimidine antagonists

fluorouracil (5-FU), cytarabine (ara-C), capecitabine, floxuridine (FUDR), gemcitabine

Antimetabolites

Folic acid antagonism Interferes with the use of folic acid As a result, DNA is not produced, and the cell dies

Antimetabolites (cont’d)

Purine antagonism Interrupts metabolic pathways of purine nucleotides Results in interruption of DNA and RNA synthesis Tumor lysis syndrome

Pyrimidine antagonism Interrupts metabolic pathways of pyrimidine bases Results in interruption of DNA and RNA synthesis

Used in combination with other drugs to treat various types of cancer, such as solid tumors and some hematologic cancers Acute and chronic lymphocytic leukemias Leukemias (several types) Colon, rectal, breast, stomach, lung, pancreatic

cancers

Antimetabolites: Indications

Oral and topical forms may be used for low-dose maintenance and palliative cancer therapy

Often used in combination chemotherapy regimens

Methotrexate is also used to treat severe cases of psoriasis and rheumatoid arthritis

Antimetabolites: Indications (cont’d)

Hair loss, nausea and vomiting, myelosuppression

Neurologic, cardiovascular, pulmonary, hepatobiliary, GI, genitourinary, dermatologic, ocular, otic, and metabolic toxicity

Tumor lysis syndrome Palmar-plantar dysesthesia (also called hand-

foot syndrome), Stevens-Johnson syndrome, toxic epidermal necrolysis

Antimetabolites: Adverse Effects

Classroom Response Question

Which condition does the nurse anticipate when assessing a patient with tumor lysis syndrome?

A.Hyperuricemia

B.Hypophosphatemia

C.Hypokalemia

D.Hypercalcemia

A patient who is receiving high-dose chemotherapy with methotrexate is also receiving leucovorin. The purpose of the leucovorin is to:

A.produce an additive effect with the methotrexate by increasing its potency against the cancer cells.

B.reduce the incidence of cardiomyopathy caused by the methotrexate.

C.add its antiinflammatory effects to the treatment regimen.

D.reduce the bone marrow suppression caused by the methotrexate.

Natural products obtained from the periwinkle plant Vinca alkaloids

Semisynthetic drugs obtained from the mandrake (mayapple) plant

Drugs obtained from the yew tree

Mitotic Inhibitors

Vinca alkaloids (periwinkle) vinblastine, vincristine, vinorelbine

Taxanes docetaxel (European yew tree: needles) paclitaxel (western yew tree: bark) cabazitaxel eribulin

Mitotic Inhibitors (cont’d)

Can work in various phases of the cell cycle (late S phase, throughout G2 phase, and M phase)

All work shortly before or during mitosis and thus retard cell division

Each different subclass inhibits mitosis in a unique way

Mitotic Inhibitors: Mechanism of Action

Often used in combination therapies Used to treat a variety of solid tumors and some

hematologic malignancies Testicular, small cell lung, breast, ovarian, non–small

cell lung cancers Kaposi’s sarcoma Acute leukemia

Mitotic Inhibitors: Indications

Hair loss, nausea and vomiting, myelosuppression

Liver, kidney, lung toxicities Convulsions Extravasation

Several specific antidotes can be used

Mitotic Inhibitors: Adverse Effects

Derived from mandrake plants Used to treat small cell lung cancer and

testicular cancer Not used as much now because of significant

toxicities without therapeutic benefit etoposide teniposide

Alkaloid Topoisomerase II Inhibitors

The nurse identifies which of the following as the most significant neurotoxin of the cytotoxic drug class?

A.paclitaxel (Taxol)

B.docetaxel (Taxotere)

C.vincristine (Vincasar PFS)

D.etoposide (Toposar)

Derived from camptothecin, a substance taken from a Chinese shrub topotecan (Hycamtin) irinotecan (CPT-11, Camptosar)

Topoisomerase 1 Inhibitors (Camptothecins)

Cell cycle–specific drugs Inhibit proper DNA function in the S phase Prevent DNA relegation

Topoisomerase 1 Inhibitors (Camptothecins) (cont’d)

Indications Ovarian and colorectal cancer Small cell lung cancer Other tumors

Adverse effects Bone marrow suppression (predictable, reversible,

noncumulative, manageable) GI effects (nausea, vomiting, diarrhea) Irinotecan causes cholinergic diarrhea (delayed,

occurring 2 to 10 days after dosage)

Synthesized using cultures of bacteria and recombinant DNA technology

As a result, an enzyme is produced This enzyme is isolated and purified for clinical

use asparaginase (Elspar): used to treat acute

lymphocytic leukemia pegaspargase (Oncaspar)

Antineoplastic Enzymes

Assess baseline blood counts before administering antineoplastic drugs

Follow specific administration guidelines for each antineoplastic drug

Nursing Implications

A pregnant woman has been diagnosed with cancer and is meeting with her oncologist to plan treatment. Which statement about chemotherapy and pregnancy is true?A.She will have to wait until the baby is born before starting chemotherapy.B.The greatest risk of fetal harm from chemotherapy is during the third trimester.C.Chemotherapy treatment during the second or third trimester poses less risk to the fetus.D.Chemotherapy is unsafe during pregnancy, but radiation therapy is safe in low doses.

Remember that all rapidly dividing cells (both normal and cancer cells) are affected Mucous membranes Hair follicles Bone marrow component

Monitor for effects on these tissues or complications

Nursing Implications (cont’d)

Monitor for complications GI mucous membranes: stomatitis, altered bowel

function with high risk for poor appetite, nausea, vomiting, diarrhea, and inflammation and possible ulcerations of GI mucosa

Monitor for complications Hair follicles: loss of hair (alopecia) Bone marrow components: dangerously low (life-

threatening) blood cell counts Monitor for adverse effects specific to the type of

antineoplastic drug given

Implement measures to monitor for and prevent infection in patients with neutropenia or leukopenia

Implement measures to monitor for and prevent bleeding in patients with thrombocytopenia and anemia

Keep in mind that anemia may result in severe fatigue

The nurse is caring for a patient who received chemotherapy 24 hours ago. The patient’s white blood cell count is 4,400 mcL. Which symptom, if experienced by the patient, should the nurse report to the prescriber immediately?

A.Fatigue

B.Diarrhea

C.Fever

D.Nausea and vomiting

Monitor for stomatitis (oral inflammation and ulcerations), and implement measures to reduce the effects if it occurs

Anticipate nausea and vomiting, and implement measures to reduce these effects

Antiemetics often work better if given 30 to 60 minutes before chemotherapy is started

Women of childbearing age will need to use a nondrug form of contraception during therapy

In addition to physical measures, keep in mind the need for emotional support during this time for both the patient and family

Monitor for therapeutic responses to antineoplastic therapies and the many possible adverse effects

When working with a patient who is neutropenic, the nurse identifies which as the most effective measure to prevent the patient from developing an infection? A.Administer prophylactic antibioticsB.Stop administration of the chemotherapeutic drugC.Perform hand hygieneD.Vaccinate the patient to prevent bacterial infection

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cell cyclespecific drugs

cellcycle stage cancer

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specific cellcycle phase

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