Chemotherapy



Chemotherapy


MiKaela Olsen



I. Definition:

Chemotherapy is the use of various chemical agents that interfere with the replication and other normal functions of cancer cells, resulting in cell death. The modern use of chemotherapy began in the 1940s with the discovery that mustard gas causes myelosuppression in those exposed to it. Further investigation with the derivative nitrogen mustard revealed a significant antitumor effect. The continued development of chemotherapeutic agents has led to dramatic improvement in survival for people with various tumor types, including childhood leukemia, Hodgkin’s and non-Hodgkin’s lymphomas, and testicular cancer. As new agents are discovered, the list of chemotherapy agents continues to grow and new classifications of chemotherapy agents are being identified.


II. Rationale for Use

A. Because malignant cells tend to divide more rapidly than normal tissue cells, chemotherapy should have a greater effect on the malignant cells.

B. Chemotherapy provides a systemic approach to the treatment of cancer. Systemic treatment is necessary for cancers that are disseminated by nature, such as leukemias, or for cancers that have metastasized.

C. The goals of chemotherapy are cure, control, or palliation.

1. Cure: Some malignancies may be cured with the use of chemotherapy alone or in conjunction with other treatment modalities. Adjuvant therapy is the use of chemotherapy in conjunction with a primary treatment in an attempt to eliminate any undetectable metastatic spread and to increase the chance of cure.

2. Control: When a cure is not a realistic goal, chemotherapy may be used to control the disease. The aim is to extend the length and improve the quality of life by preventing development of new problems and symptoms.

3. Palliation: When neither cure nor control of the malignancy is possible, chemotherapy may be used to reduce the tumor burden and related symptoms and possibly improve the quality of life.


III. Biology of Therapy

A. Cell Cycle Phase: Cells undergoing replication move through several phases. These phases occur in both normal and malignant cells (Fig. 6-1). Cells are most sensitive to chemotherapeutic agents while they are actively dividing. Some chemotherapy drugs work only during specific phases of the cell division cycle (cell cycle specific), whereas others work throughout the process (cell cycle nonspecific).

B. Tumor Sensitivity to Chemotherapy: Tumors with a large number of dividing cells are more sensitive to chemotherapy drugs than tumors with more cells in the resting phase. Tumors can also develop resistance to
chemotherapy drugs over time. Treatment approaches that can decrease the development of resistance include administering dose-intensive regimens (higher doses over a shorter period of time), alternating drugs with each treatment course, and shortening the intervals between treatments.






Figure 6-1. Phases of the cell cycle. (Porth, C. M. [1994]. Pathophysiology: Concepts of altered health states [4th ed.]. Philadelphia: J. B. Lippincott.)

C. Combination Therapy: Although single agents are sometimes used in the treatment of cancer, combination drug therapy is increasingly becoming the norm. By combining agents, more malignant cells should be caught in a sensitive phase, resulting in a larger tumor cell kill. Several principles underlie the selection of agents for combination therapies.

1. Each drug must show efficacy in the specific tumor type.

2. The drugs chosen should have a synergistic effect or potentiate each other.

3. The drugs should have different mechanisms of action and, therefore, affect the cell in different manners.

4. The drugs should have different side effects, or similar side effects that occur at different times.

D. Repeat Dosing: Seldom will all cells in a tumor be affected by a single course of chemotherapy. Most chemotherapy regimens involve several cycles (courses) of chemotherapy repeated at specific intervals. With each repeated dose of chemotherapy, more of the cancer cells are killed, with the goal of eliminating the majority of the tumor to allow the patient’s immune system to destroy any remaining cancer cells.


IV. Types of Chemotherapy Drugs:

Chemotherapy drugs are classified according to how they interfere with cell division and maintenance. Table 6-1 lists commonly used chemotherapy classifications with indications and side effects.


A. Alkylating agents act by cross-linking strands of DNA, thus preventing transcription of RNA and replication of DNA. These agents can affect cells during various phases of cell division and are, therefore, cell cycle nonspecific.

B. Antimetabolites act during the S phase, interfering with DNA and RNA synthesis. These agents are considered cell cycle specific.

C. Antitumor antibiotics interfere with DNA synthesis by binding with the DNA at various points and preventing RNA synthesis. These agents may also alter the cell membrane and inhibit certain enzymes. They are cell cycle nonspecific.

D. Nitrosureas interfere with DNA synthesis and can damage the DNA helix. These agents are cell cycle specific.

E. Vinca alkaloids act in G1, G2, and M phases. They block production of DNA and prevent cell division. Vinca alkaloids are cell cycle specific.

F. Taxanes prevent depolymerization of microtubules. Paclitaxel acts in the G2 and M phases, whereas docetaxel acts primarily in the S phase. Taxanes are considered cell cycle specific.

G. Camptothecins act in the S phase and are known as topoisomerase I inhibitors. When topoisomerase I is inhibited, DNA damage occurs. Camptothecins are cell cycle specific.

H. Epipodophyllotoxins interfere with topoisomerase II, causing damage in the G2 and S phases. They are cell cycle specific.

I. Miscellaneous agents work in a variety of ways. Asparaginase agents and procarbazine both work by inhibiting protein synthesis. These are considered cell cycle specific agents.

J. Tyrosine kinase inhibitors decrease proliferation of tumor cells and induce apoptosis.

K. Proteosome inhibitors induce apoptosis in tumor cells by blocking proteosome.

L. Hormones and hormone antagonists interfere with cellular function and growth in sensitive tissues. Corticosteroids can suppress the production of abnormal lymphocytes. Antiandrogens and antiestrogens can be administered to interfere with the replication of tumors that proliferate in the presence of these hormones, such as certain prostate and breast cancers.


V. Nursing Issues

A. Administration: Chemotherapy can be administered by several different routes depending on the drug being administered, as well as on the tumor type and location.

1. The intravenous (IV) route allows administration of chemotherapy directly into the blood, allowing more precise control of dose and decreasing absorption issues. It is the most commonly used method.

a. The peripheral route allows access to the blood without more invasive procedures. The peripheral route is best suited to patients undergoing short-term therapy who have healthy peripheral veins.

b. The central route can be accessed by using a variety of central venous access devices. The choice of catheter depends on such issues as length of anticipated use, frequency with which the device will be accessed, ability of the patient and caregiver to care for the device, type of treatment to be given, patient factors that may contraindicate an invasive procedure, and patient preference.












TABLE 6-1 Commonly Used Chemotherapy Classifications With Indications and Side Effects













































































Chemotherapy Agent and Classification

Adverse Effects

Special Nursing Implications


Alkylating Agents


Busulfan (Myleran)
Carboplatin (Paraplatin)
Cisplatin (CDDP, Platinol)
Melphalan (Alkeran)
Cyclophosphamide (Cytoxan)
Dacarbazine (DTIC)
Ifosfamide (Ifex)
Mechlorethamine hydrochloride (Nitrogen mustard)
Thiotepa (Thioplex)
Chlorambucil (Leukeran)
Eloxatin (Oxaliplatin)

Myelosuppression, fatigue, nausea, vomiting, mucositis, liver and renal toxicities, second malignancies, peripheral neuropathy, suppressed sperm production and ovarian function

Seizures can occur with high doses of busulfan; administer anticonvulsant.
Ototoxicity can occur with cisplatin and carboplatin.
Cisplatin causes electrolyte wasting; replace and monitor electrolytes as needed.
Amifostine may be used as a renal protectant with cisplatin.
Myelosuppression can be delayed with melphalan (4-6 weeks in length).
Melphalan and dacarbazine are irritants. Dilute drugs during administration.
Hemorrhagic cystitis occurs with ifosfamide and cytoxan. Prehydration and mesna are used for prevention.
Nitrogen mustard is a vesicant and irritant; administer through a side port of a free-flowing IV and flush with ≥ 125 mL of normal saline at the completion.
Eloxatin is associated with pharyngolaryngeal dysesthesia seen in 1% to 2% of patients, characterized by subjective sensations of dysphagia or dyspnea, without any laryngospasm or bronchospasm.
Thiotepa can cause severe skin toxicity in high doses.


Antimetabolites


Cladribine (Leustatin)
Cytarabine (cytosine arabinoside, ara-C, Cytosar-U)
Cytarabine liposomal (DepoCyt)
Floxuridine (FUDR)
Fluorouracil (5-fluorouracil, 5-FU)
Methotrexate (MTX, Amethopterin Folex)
Mercaptopurine (6-MP, Purinethol)
Thioguanine (6-thioguanine, 6-TG)
Fludarabine (Fludara)
Capecitabine (Xeloda)
Gemcitabine (Gemzar)
Deoxycoformycin (Pentostatin, Nipent)
Hydroxyurea (Hydrea, Mylocel)

Myelosuppression, fatigue, nausea, vomiting, mucositis, liver and renal toxicities, rash, photosensitivity, palmar plantar erythro-dyskesthesia, diarrhea, fever, interstitial pneumonitis, alopecia, hyperpigmentation of skin and veins.

Cytarabine in high doses given as a bolus infusion can cause cerebellar toxicity. Monitor patients for the inability to do rapid alternating hand movements, unsteady gait, nystagmus, slurred speech. Hold cytarabine and notify physician immediately for these symptoms.
Cytarabine in high doses given in a continuous infusion causes pulmonary toxicity. Monitor fluid status and lungs closely.
Cytarabine in high doses causes chemical conjunctivitis. Administer steroid eye drops as ordered.
Fluorouracil is often given concurrently with leucovorin.
Warn patients to avoid sun exposure while on these medications.
High doses of methotrexate must be administered with aggressive hydration, sodium bicarbonate to alkalanize the urine, and leucovorin, which is started 24 hours after methotrexate as a rescue agent.
Pentostatin is used investigationally for graft-versus-host disease.


Antitumor Antibiotics


Bleomycin (Blenoxane)
Dactinomycin (Actinomycin D, Cosmegen)
Daunorubicin (daunomycin, Cerubidine)
Doxorubin (Adriamycin, Rubex)
Doxorubicin HCI (liposome) (Doxil)
Idarubicin (Idamycin)
Mitomycin (Mutamycin)
Mitoxantrone (Novantrone)
Plicamycin (Mithramycin, Mithracin)

Myelosuppression, fatigue, nausea, vomiting, mucositis, cardiotoxicity, liver and renal toxicities, alopecia, suppressed sperm production and ovarian function

All antitumor antibiotics are vesicants except bleomycin, Doxil, and mitoxantrone.
Administer vesicants through a side port of a free-flowing IV.
Follow institutional guidelines for bleomycin administration if test dose is required. Fever and chills frequently occur after bleomycin administration. Acetominophen can be used in the first 24 hours.
Dactinomycin is ordered in micrograms. Use caution with administration.
Red discoloration of urine can occur 1-2 days after treatment with dactinomycin, doxorubicin, and daunorubicin.
Blue/green discoloration of urine or sclera can occur 1-2 days after treatment with mitoxantrone.
Cumulative lifetime doses:
Bleomycin = 400 units
Idarubicin = 150 mg/m2
Mitoxantrone = 140 mg/m2
Doxorubicin = 550 mg/m2*
*If patient has history of chest radiation, then decrease to 450 mg/m2.


Nitrosureas


Carmustine (BCNU)
Lomustine (CCNU)
Streptozocin (Zanosar)

Myelosuppression, fatigue, nausea, vomiting, mucositis, liver and renal toxicities, pulmonary toxicity, alopecia, suppressed sperm production and ovarian function

Nitrosureas are associated with a delayed nadir of approximately 4-6 weeks.
Do not administer more frequently than every 4-6 weeks.
Nitrosureas cross the blood-brain barrier.
Carmustine is an irritant. Flush with ≥150 mL normal saline after administration.


Vinca Alkaloids


Vinblastine (Velban)
Vincristine (Oncovin, Vincasar, Vincrex)
Vinorelbine (Navelbine)

Myelosuppression (mild with vincristine), fatigue, nausea, vomiting, mucositis, liver toxicity, peripheral neuropathy, constipation, alopecia, paralytic ileus, trigeminal nerve toxicity

All vinca alkaloids are vesicants. Administer through a side port of a free-flowing IV.
If extravasation occurs, apply warm compresses per institutional guidelines.
Maximum single dose of vincristine is 2 mg.


Taxanes


Paclitaxel (Taxol)
Docetaxel (Taxotere)

Myelosuppression, fatigue, hypersensitivity reactions, mild nausea, vomiting, myalgias, flulike symptoms, peripheral neuropathy, alopecia, cardiac toxicities, fluid retention with docetaxel

Paclitaxel premeds—steroid, h2 blocker, and antihistamine
Docetaxel premeds—steroids (for prevention of fluid retention)
Non-PVC tubing required for infusion of both paclitaxel and docetaxel
0.2-micron in-line filter required for paclitaxel administration


Camptothecins


Topotecan (Hycamtin)
Irinotecan (Camptosar, CPT-11)

Myelosuppression, fatigue, nausea, vomiting, alopecia, diarrhea

Irinotecan is associated with early (acute, during administration, or within 24 hours) and late diarrhea. Early-onset diarrhea is treated with atropine, and late-onset diarrhea is treated with Imodium. Patient teaching regarding the onset, associated signs and symptoms, and management of diarrhea is essential.


Epipodophyllotoxins


Etoposide (VP-16, Etopophos, VePesid)
Teniposide (VM-26, Vumon)

Myelosuppression, fatigue, nausea, vomiting, alopecia, hypotension, hypersensitivity reactions.

Rapid administration of these drugs results in hypotension.
High doses precipitate in IV tubing and need to be diluted according to manufacturer guidelines.


Miscellaneous Agents


Asparaginase (Elspar)
Pegasparaginase (Oncaspar)
Procarbazine (Matulane)
Arsenic trioxide (Trisenox)

Myelosuppression, fatigue, nausea, vomiting, alopecia, hypersensitivity reactions, liver toxicity. ECG changes and APL differentiation syndrome with Trisenox administration.

An intradermal test dose of asparaginase may be used based on institutional guidelines.
Hyperglycemia, pancreatitis, and alterations in coagulation factors are potential toxicities that can occur with asparaginase and pegasparaginase. Monitor closely.
Polyethylene glycol (PEG) attached to the asparaginase decreases the immunogenicity and increases the half-life.
Procarbazine should not be taken with foods high in tyramine (eg, aged cheeses, avocados, bananas, beer, caffeinated beverages, chocolate, sausages, liver, over-ripe fruit, red wine, smoked or pickled fish, yeast, and yogurt).


Tyrosine Kinase Inhibitors


Gefitinib (Iressa)

Diarrhea, nausea, vomiting, rash, liver toxicity, lung toxicity, corneal erosions

Oral chemotherapy drug
Interstitial lung disease occurs in approximately 1% of patients on Iressa and can be fatal.


Imatinib mesylate (Gleevec)

Nausea, vomiting, fluid retention, neutropenia, hepatotoxicity

Check drug compatibilities carefully.
Instruct patient to take with food.


Proteasome Inhibitors


Bortezomib (Velcade)

Myelosuppression, nausea, vomiting, diarrhea, anorexia, constipation, peripheral neuropathy, fever, edema, asthenia

Indicated for multiple myeloma and under investigation in other malignancies

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Sep 16, 2016 | Posted by in NURSING | Comments Off on Chemotherapy

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