Introduction to Pharmacology – CHAPTER 21 Antineoplastic Drugs

1 Identify antineoplastic drugs, and understand their different modes of action.
2 Explain the use of antineoplastic drugs in immunosuppressive therapy.
3 Understand the use of hormones in the treatment of certain tumors.
4 Understand and anticipate the toxic effects of antineoplastic agents.
5 Discuss nursing measures that provide supportive therapy for cancer patients.

Neoplastic diseases, or cancers
Are caused by abnormal and uncontrolled growths known as neoplasms.

malignancies are
Neoplasms that invade surrounding and distant healthy tissues or organs, interfering with function and capable of causing the death of the entire organism.

carcinoma
Is a malignancy arising from the epithelial cells. Of malignancies, 80% can be defined as carcinomas, but in common practice, the terms malignancy and carcinoma are often used interchangeably.

antineoplastic drugs
Surgery and radiation are still the primary treatment modalities for malignant diseases.
Drugs used to treat cancer— have a very important role in the treatment of certain tumors. Systemic drug treatment is important when cancer is widespread or when the organ or tissue cannot be removed.

Antineoplastic drugs are also used after surgical removal of a cancer to treat microscopic disease that may be left behind.

antineoplastic drugs -1
Because the malignant cell is dividing more rapidly than normal cells, it is more sensitive than normal cells to antineoplastic agents, which interfere with cell growth or metabolism.

antineoplastic drugs -2
The main disadvantage of cancer drugs is that they are often toxic to normal cells as well.

The more rapidly dividing healthy tissues (e.g., gastrointestinal [GI] epithelium, oral mucosa, bone marrow, lymphoid tissue, and gonads) are the first to be affected by antineoplastic drugs, and too much tissue destruction in these areas can require withdrawal of the antineoplastic drug before the disease is brought under control.

Antineoplastic drugs may be classified as follows:
1. Alkylating agents attach “alkyl groups,” or organic side chains, to the proteins or DNA within the cancer cell, interfering with its function.
2. Antimetabolites interfere with some phase of normal cellular metabolism. Antimetabolites are substances that compete with, replace, or antagonize a metabolic or bodily function.
3. Hormones may antagonize certain tumors of the reproductive tract and accessory sex organs by altering normal hormonal balance.
4. Antitumor antibiotics act usually by interfering with DNA or RNA synthesis.
5. Enzyme inhibitors interfere with tumor enzymes.
6. Immunomodulating agents enhance the body’s own defense mechanisms to attack the cancer cells.
7. Molecular medicine and targeted therapy treat cancer at the cellular level with agents that are specifically developed to arrest cancer at the cellular level.
8. Platinum-containing agents disrupt the function of DNA and proteins because the platinum component of the drugs binds to the DNA and proteins.
9. Vaccines stimulate the individual’s own immune system to destroy the cancer cells.
10. Miscellaneous drugs are a heterogeneous group of drugs having various mechanisms of action.

ALKYLATING AGENTS
Alter the chemical composition of proteins, probably the nucleoproteins, of the cell. The cell cannot function normally in the presence of these abnormal molecules. Alkylating agents were one of the first forms of antineoplastic therapy and have remained in use because of their undisputed effectiveness in the palliation of certain types of cancer. They are all highly toxic compounds, however, and produce many unpleasant and dangerous side effects with continued use.

busulfan, USP-NF, BP (Myleran).
Busulfan is administered orally and is used primarily for malignancies of the blood-forming organs.

carmustine (BiCNU).
This alkylating agent is a derivative of nitrosourea. It is used primarily in the treatment of malignant brain tumors. The most serious and frequent side effect is a cumulative and delayed bone marrow toxicity that usually occurs 4 to 6 weeks after therapy. Nausea, vomiting, renal toxicity, hepatotoxicity, and skin rashes occur.

chlorambucil, USP-NF, BP (Leukeran).
Chlorambucil has its greatest effect on the blood-forming tissues; it is used primarily in the treatment of leukemias and malignancies of the lymphatic system. It is most commonly used in the treatment of chronic lymphocytic leukemia. Chlorambucil has an advantage over mechlorethamine in that it can be administered orally. Side effects include nausea, vomiting, diarrhea, bone marrow suppression, and dermatitis..

cyclophosphamide,USP-NF,BP (Cytoxan).

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Cyclophosphamide may be administered orally, intramuscularly, intravenously, or as an intracavitary infusion. It is most often used in treatment of breast cancer, nonHodgkin’s lymphoma, chronic lymphocytic leukemia, ovarian carcinoma, sarcoma, and Wilms’ tumors. It may also be used as an immunosuppressant in diseases such as lupus erythematosus. Side effects include nausea, vomiting, diarrhea, bone marrow suppression, and dermatitis. After administration, there is an increased risk of hemorrhagic cystitis and secondary malignancies such as bladder cancer.

ifosfamide (Ifex)
Ifosfamide is structurally related to cyclophosphamide. It is particularly useful in the treatment of germ cell testicular neoplasms, sarcomas, and lymphomas. Side effects are similar to side effects of cyclophosphamide.

lomustine (CCNU).
This agent is well absorbed from the GI tract and is generally administered orally, although it may be used as a topical application in certain cases. It is used in the treatment of brain tumors, lymphomas, and tumors of the GI tract and kidney. It has been used topically to treat mycosis fungoides and psoriasis. Delayed bone marrow toxicity, nausea, vomiting, alopecia, liver and kidney toxicity, and skin reactions occur with therapy.

melphalan, USP-NF, BP (Alkeran)
Melphalan is used alone and in combination with other antineoplastic agents to treat multiple myeloma and amyloidosis. Side effects include bone marrow toxicity, nausea, vomiting, alopecia, and liver and kidney toxicity.

procarbazine (Matulane)
This agent is used in the treatment of brain tumors and lymphomas. It is a weak monoamine oxidase inhibitor and should not be used with tricyclic antidepressants, sympathomimetic drugs, alcohol, or foods high in tyramine. Concurrent use with central nervous system (CNS) depressants or antihistamines may lead to respiratory depression. Other side effects are similar to the side effects of the other drugs in this class and include nausea, vomiting, alopecia, and bone marrow toxicity.

temozolomide (Temodar)
Temozolomide is used to treat brain tumors, such as glioblastoma multiforme, and melanoma. Thrombocytopenia and neutropenia are dose-limiting toxicities. Nausea, vomiting, and headache are also seen.

thiotepa, USP-NF, BP.
Thiotepa is administered topically or as an intracavitary infusion as well as intravenously or intramuscularly. It is primarily used to treat cancer of the reproductive tract, lymphomas, leukemias, and bladder cancer. It is often instilled in the pleural space to decrease pulmonary effusions that occur with local neoplastic diseases. It is occasionally instilled in the bladder to aid in the treatment of small bladder tumors by topical action. Side effects are similar to the side effects of the other drugs within this group.

ANTIMETABOLITES
Are antineoplastic drugs that act by interfering with a specific phase of cell metabolism. Because neoplastic cells grow more rapidly than normal cells, theoretically they should be affected by these drugs at dosage levels that cause only minimal interruption in the metabolism of normal cells. This theory does not always prove to be true, however, and severe bone marrow suppression in particular occurs very often, requiring withdrawal of the drug. Loss of the GI epithelium and ulcers of the oral mucosa are also frequent side effects of antimetabolites.

azacitidine (Vidaza).
This agent inhibits DNA methylation. It is approved for the treatment of myelodysplastic syndrome. Side effects include cytopenia, GI side effects, and elevated liver enzymes.

capecitabine (Xeloda).
Capecitabine is an oral version of fluorouracil (5-FU) used to treat metastatic breast cancer and GI malignancies. This agent acts as a radiation sensitizer, and lower doses may be administered if given concurrently with radiation. Side effects include nausea, vomiting, diarrhea, abdominal pain, stomatitis, edema, paresthesias, and hyperbilirubinemia. Often the hands and feet become dry and painful.
Capecitabine is contraindicated in patients allergic to 5-FU.

cladribine (Leustatin, 2-Cda).
Cladribine is indicated for the treatment of hairy cell leukemia. Side effects include nephrotoxicity, bone marrow suppression, nausea, vomiting, headache, and edema.

clofarabine (Clolar).
This agent interferes with DNA replication and is given for relapsed or refractory acute lymphocytic leukemia. Side effects include myelosuppression (suppression of the bone marrow), edema, hypotension, nausea, vomiting, renal toxicity, and hepatotoxicity.

cytarabine, USP-NF, BP (Ara-C, Cytosar-U).
The antimetabolic effect of cytarabine seems to occur by interference with DNA formation. It is used primarily to treat acute myelocytic leukemia in adults, although it has been used to treat other adult and childhood leukemias. It may be used intrathecally for meningeal leukemia. Primary side effects are suppression of bone marrow and GI symptoms. Fever, rash, cellulitis, pain at the injection site, sore throat, conjunctivitis, and alopecia also occur frequently. Cerebellar side effects may be observed, and arachnoiditis is a common side effect when cytarabine is used intrathecally.

dacarbazine (DTIC-Dome).

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This agent has many uses, including treatment of melanoma and Hodgkin’s disease. Side effects include adverse hematologic, hepatic, and GI symptoms.

decitabine (Dacogen).
Decitabine interferes with DNA replication and inhibits methylation of DNA. It is used in the treatment of myelodysplastic syndrome. Side effects include myelosuppression, nausea, vomiting, and elevated bilirubin.

floxuridine, USP-NF, BP (FUDR).
By interfering with the synthesis of DNA, floxuridine has been found to be beneficial in certain malignancies. It is recommended only for intrahepatic arterial infusion and is used primarily for treatment of metastatic GI carcinoma confined to the liver. Side effects are generally related to the area where the drug was infused but can include oral stomatitis, esophagopharyngitis, duodenal ulcer, liver toxicity, and GI bleeding. Localized erythema, ataxia, blurred vision, and vertigo have also been noted.

fludarabine phosphate (Fludara).
Many malignancies are treated with fludarabine, including chronic lymphocytic leukemia and non-Hodgkin’s lymphoma. It has no activity in solid tumors. Side effects are dose-related and include neurotoxicity and myelosuppression.

fluorouracil, USP-NF (5-FU).
5-FU is a chemical analog of uracil, a component of RNA. When incorporated into the RNA molecule, it interferes with normal growth and metabolism of the cell. It is administered intravenously for the treatment of breast cancer, GI malignancies, head and neck cancer, and ovarian cancer. It may also be applied topically to treat actinic keratoses.

gemcitabine hydrochloride (Gemzar).
Gemcitabine is used to treat adenocarcinoma of the pancreas and lung and bladder cancer. Side effects include hematologic toxicity. Gemcitabine should be given with caution to patients with renal and hepatic impairment.

mercaptopurine, USP-NF (Purinethol, 6-MP).
Mercap topurine is an antimetabolite that inhibits the synthesis of purines (components of DNA). It is administered orally and is effective in the treatment of acute lymphoblastic leukemias, Hodgkin’s disease, and other tumors of the lymphatic system. Toxicity includes immunosuppression with increased risk of infection and nausea and vomiting.

methotrexate, USP-NF, BP (Amethopterin).
Mercap topurine is an antimetabolite that inhibits the synthesis of purines (components of DNA). It is administered orally and is effective in the treatment of acute lymphoblastic leukemias, Hodgkin’s disease, and other tumors of the lymphatic system. Toxicity includes immunosuppression with increased risk of infection and nausea and vomiting. Methotrexate has been used effectively to treat uterine choriocarcinoma, breast cancer, sarcomas, adult leukemias, non-Hodgkin’s lymphoma, bladder cancer, and carcinomatous meningitis. It is also effective in the treatment of psoriasis, psoriatic arthritis, and rheumatoid arthritis. Methotrexate is commonly administered orally but is also available in a parenteral form that may be given intramuscularly, intravenously, intra-arterially, or intrathecally (within the spinal cord). Side effects include myelosuppression; mucositis; and renal, liver, lung, and neural toxicity. The dosage of this drug varies widely because of its many uses.

pemetrexed (Alimta).
Pemetrexed is a folic acid antagonist that is used to treat small cell lung cancer and mesothelioma. The patient must be started on folic acid and vitamin B12 supplementation before starting the drug. Oral corticosteroids are generally administered before and after treatment to reduce the severity of the dermatologic reactions. Side effects include myelosuppression, GI distress, skin rash, and elevation of liver enzymes.

6-thioguanine, 6-TG (Tabloid).
This agent is used to treat acute myelogenous and lymphocytic leukemia, Hodgkin’s lymphoma, multiple myeloma, and solid tumors. There is usually cross-resistance between mercaptopurine and thioguanine. Side effects include myelosuppression, pancytopenia, hyperuricemia, nausea, vomiting, intestinal necrosis, and perforations.

HORMONES
Hormones have various uses in the treatment of malignant diseases.

Corticosteroids
(Hormones produced by the adrenal cortex and their synthetic forms) have long been shown to be valuable in producing remissions of certain malignancies, notably acute lymphocytic leukemia of childhood. They are used either alone or in combination with other drugs. The mechanism of action is not fully understood. Corticosteroids have been used with less effectiveness in the treatment of Hodgkin’s disease, nonHodgkin’s lymphoma, chronic lymphocytic leukemia, prostate cancer, and multiple myeloma. Side effects are those of excessive administration of corticosteroids (i.e., salt and water retention, moon facies, edema, and striae). In many cases, dietary salt may have to be strictly curtailed during administration. Prednisone is perhaps used more than any other corticosteroid in treating malignancies, but other compounds, such as dexamethasone (Decadron), are similarly effective.

ANTIANDROGENS
bicalutamide (Casodex).
Generally, this agent is used in combination therapy for the treatment of metastatic cancer of the prostate. Side effects include hot flashes, loss of libido, impotence, gynecomastia, galactorrhea, GI symptoms, and occasionally elevation of the liver enzymes.

flutamide (Eulexin).
Flutamide is an orally active antiandrogen used to treat metastatic cancer of the prostate. Side effects include hot flashes, loss of libido, impotence, galactorrhea, gynecomastia, impotence, drowsiness, anemia, and edema. A yellow-green urine may be noted.

nilutamide (Nilandron).

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Nilutamide is a nonsteroidal, orally active antiandrogen. It is used to treat metastatic prostate cancer. Side effects include hot flashes, loss of libido, impotence, gynecomastia, galactorrhea, hepatic impairment, respiratory insufficiency, and interstitial pneumonia.

Estrogens
Sex hormones have been used to palliate carcinomas of the reproductive tract. Estrogens, steroids responsible for feminine characteristics, may be administered to men with carcinoma of the prostate.

estramustine phosphate sodium (Emcyt).
Estramustine is a conjugate of 17-beta-estradiol and nornitrogen mustard. It is used to treat metastatic prostate cancer and exerts its effect by inhibiting cell division. Absorption is significantly decreased when it is given with dairy products or other calcium-rich foods. Side effects include nausea, vomiting, diarrhea, angioedema, thromboembolic disorders, and cardiovascular hepatic effects.

megestrol acetate (Megace).
Chemically related to progesterone, megestrol is used to treat endometrial carcinoma, breast cancer, endometriosis, and prostatic hypertrophy. It is also used as an appetite stimulant for cachexia from various causes, including acquired immunodeficiency syndrome (AIDS) (see Chapter 17). Very few side effects occur with this agent. It should be used with caution in patients with a history of thrombophlebitis. It may be associated with a tumor flare (i.e., the tumor gets larger before reducing in size).

ANTIESTROGENS
fulvestrant (Faslodex).
Fulvestrant is used to treat metastatic breast cancer in women who have had a recurrence after tamoxifen or aromatase inhibitor therapy. Side effects include hematologic disorders and GI effects of nausea, vomiting, diarrhea, and abdominal pain.

SELECTIVE ESTROGEN RECEPTOR MODULATORS
Within the antiestrogens is a group known as selective estrogen receptor modulators (SERMs). SERMs exert selective agonist or antagonist effects on various estrogen target tissues. These agents are chemically diverse but possess a tertiary structure that allows them to bind to the estrogen receptor. Because of their estrogen receptor-activating properties, SERMs can be used to prevent or treat diseases caused by estrogen deficiency, such as osteoporosis. Because of their estrogen receptor- blocking properties, they can also be used to prevent or treat diseases such as breast cancer.

(SERMs)
selective estrogen receptor modulators
SERMs exert selective agonist or antagonist effects on various estrogen target tissues. These agents are chemically diverse but possess a tertiary structure that allows them to bind to the estrogen receptor.
Because of their estrogen receptor-activating properties, SERMs can be used to prevent or treat diseases caused by estrogen deficiency, such as osteoporosis. Because of their estrogen receptor- blocking properties, they can also be used to prevent or treat diseases such as breast cancer.

Currently available SERMs have two major limitations:
1. They are only weak estrogen agonists, and they aggravate hot flashes. Side effects generally include nausea, vomiting, headache, hot flashes, constipation, and abdominal pain.
2. There is an increased risk of blood clots, stroke, and endometrial carcinoma after administration. The patient should be monitored for cataracts.

tamoxifen citrate (Nolvadex).
This antiestrogenic compound is similar to clomiphene. It competes with estradiol for receptor sites in tumors of the breast, uterus, and vagina and in other tumors with estrogen receptors. Its primary use is in the treatment of advanced breast cancer in postmenopausal women, but it has been studied in premenopausal women as well.

toremifene citrate (Fareston).
Toremifene is indicated for the treatment of metastatic breast cancer in postmenopausal women. Side effects include hypercalcemia, leukopenia, and vaginal bleeding. It should not be used in patients with a history of thromboembolic disease.

AROMATASE INHIBITORS
Aromatase inhibitors are used to treat advanced breast cancer in postmenopausal women or may be given after surgical removal of the tumor. Many breast cancers contain aromatase, an enzyme found primarily in adipose tissue that converts a naturally occurring adrenal hormone to additional estrogen. The activity of this enzyme leads to estrogen production even in postmenopausal women. This estrogen production is a disadvantage when treating breast cancer. Aromatase inhibitors interfere with this process of estrogen production and can lead to diminished tumor growth. The side effects are notably similar to menopausal symptoms: hot flashes, weight gain, mood changes, and most notably osteoporosis and fractures.

anastrozole (Arimidex) Dosage:
Adults only: (Oral) 1 mg daily.
Adults only: (Oral) 1 mg daily.

exemestane (Aromasin) Dosage:
Adults only: (Oral) 25 mg once daily.
Adults only: (Oral) 25 mg once daily.

letrozole (Femara) Dosage:
Adults only: (Oral) 2.5 mg daily.
Adults only: (Oral) 2.5 mg daily

INHIBITORS OF PITUITARY HORMONES
goserelin acetate (Zoladex).
Goserelin acetate is a synthetic analog of gonadotropin-releasing hormone that is used for its endocrine effects. It reduces the amount of testosterone or estrogen in the bloodstream. It is used for the treatment of prostate and breast cancer and for endometriosis and dysfunctional uterine bleeding. Side effects include hot flashes, sexual dysfunction, headaches, blood pressure instability, rash, dizziness, elevated serum cholesterol, and occasionally a tumor flare (temporary increase in the size of the tumor).

leuprolide acetate (Eligard, Lupron, Viadur).
Another synthetic analog of gonadotropin-releasing hormone, leuprolide can be used for its antineoplastic and endocrine effects. Its uses and side effects are similar to those of goserelin acetate, but it additionally is used to treat precocious puberty.

triptorelin pamoate (Trelstar).
Also an analog of gonadotropin-releasing hormone, triptorelin pamoate has actions and uses similar to the other drugs in this category. It is used in the palliative treatment of prostate cancer.

ANTITUMOR ANTIBIOTICS
bleomycin sulfate, USP-NF, BP (Blenoxane).
The antibiotic action of bleomycin apparently occurs by causing a splitting of the DNA chain. It is used in the treatment of Hodgkin’s disease and squamous cell carcinomas of the skin, penis, vulva, head, neck, and larynx. In contrast to most antineoplastic agents, this drug has a very low incidence of bone marrow toxicity. The most serious toxic effect is interstitial pneumonitis. Skin or mucocutaneous lesions, alopecia, fever, chills, and hypotension have been reported. Liver enzymes must be checked monthly while a patient is receiving this drug.

dactinomycin, USP-NF, BP (Actinomycin D, Cosmegen).
Dactinomycin is an antibiotic that exerts its effect as an antineoplastic agent by interfering with both DNA and RNA synthesis. It also inhibits DNA replication. It is used in the treatment of Wilms’ tumor of the kidney and for control of the metastases of this tumor. It has been used in combination with other agents in the treatment of metastatic tumors of the testes, choriocarcinoma, and certain lymphomas. Toxic effects include bone marrow suppression, liver and kidney toxicity, nausea, vomiting, oral stomatitis, anorexia, alopecia, and various skin eruptions.

daunorubicin hydrochloride (Daunomycin).
Daunorubicin works by inhibiting DNA and RNA synthesis and by inhibiting the unwinding of the DNA, a function necessary for replication. It is used primarily to treat acute myelogenous leukemia. It has also been used to treat lymphocytic leukemias and disseminated neuroblastoma. Side effects include myelosuppression, GI toxicity, red-orange discoloration of the urine and contact lenses, and alopecia. It may cause acute and delayed cardiotoxicity including arrhythmias and congestive heart failure. Care must be taken to avoid extravasation because it is a potent vesicant.

daunorubicin liposome (Daunoxome).
This agent is daunorubicin with liposomal encapsulation. It is used as a first-line agent for human immunodeficiency virus (HIV)-associated Kaposi’s sarcoma. The mechanism of action and side effects are similar to the parent compound.
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doxorubicin hydrochloride, USP-NF, BP (Adriamycin).
Daunorubicin works by inhibiting DNA and RNA synthesis and by inhibiting the unwinding of the DNA, a function necessary for replication. It is used primarily to treat acute myelogenous leukemia. It has also been used to treat lymphocytic leukemias and disseminated neuroblastoma. Side effects include myelosuppression, GI toxicity, red-orange discoloration of the urine and contact lenses, and alopecia. It may cause acute and delayed cardiotoxicity including arrhythmias and congestive heart failure. Care must be taken to avoid extravasation because it is a potent vesicant.

doxorubicin liposome (Doxil).
This liposomal encapsulated version of doxorubicin has a mechanism of action and side effects similar to doxorubicin. It is used to treat Kaposi’s sarcoma, ovarian carcinoma, and multiple myeloma.

epirubicin hydrochloride (Ellence).
Related to doxorubicin, epirubicin hydrochloride is used to treat breast cancer. Side effects are similar to the side effects of its parent compound.

idarubicin hydrochloride (Idamycin).
This agent is an analog of daunorubicin and also inhibits nucleic acid synthesis. It is used in combination with other antileukemic drugs to treat acute myeloid leukemia in adults. Side effects include tissue necrosis at the site of injection, myelosuppression, myocardial toxicity, nausea, vomiting, and peripheral neuropathy. Red discoloration of the urine may occur.

mitomycin C, USP-NF, BP (Mitomycin).
This antibiotic is used in conjunction with 5-FU or radiation therapy or both to treat adenocarcinoma of the stomach, pancreas, colon, and rectum; squamous cell carcinomas of the lungs, cervix, head, and neck; and malignant melanoma. Bone marrow suppression can lead to fatal sepsis if not monitored. Mouth ulcers, nausea, vomiting, and renal toxicity are among the side effects seen after administration. Hemolytic uremic syndrome has been reported.

mitoxantrone hydrochloride (Novantrone).
This synthetic antineoplastic agent is used to treat acute myelogenous leukemia and advanced prostate cancer. It also has activity in malignancies such as breast cancer and non-Hodgkin’s lymphoma. Side effects include bone marrow suppression, cardiotoxicity, nausea, vomiting, fatigue, and hemorrhage. There may be blue discoloration of the urine, sclera, and fingernails after 1 to 2 days of administration.

pentostatin (Nipent).
Pentostatin is indicated for the treatment of hairy cell leukemia. Side effects include renal, liver, pulmonary, and CNS toxicities.

streptozocin (Zanosar).
This antibiotic is produced by Streptomyces achromogenes. It is used to treat pancreatic islet cell carcinoma, carcinoid tumor, Hodgkin’s disease, and colorectal cancer. The most serious side effect is nephrotoxicity, which occurs in up to 75% of patients. Nausea, vomiting, bone marrow suppression, tissue necrosis, confusion, and depression have also been reported.

valrubicin (Valstar).
Valrubicin is a semisynthetic analog of doxorubicin. It is used for instillation into the urinary bladder for carcinoma in situ of the bladder. Side effects include bladder spasm, hematuria, incontinence, pelvic pain, vomiting, diarrhea, and peripheral edema.

ENZYME INHIBITORS
asparaginase, L-asparaginase (Elspar).
This enzyme, derived from Escherichia coli, is mainly used in combination chemotherapy for childhood acute lymphocytic leukemia, but it is used in adults as well. Side effects include skin rashes and various hepatic, renal, and hematologic effects.

etoposide, VP-16 (VePesid).
Etoposide is a natural product of the mandrake plant. It inhibits an enzyme that is important in the unwinding of the DNA during replication. It is active in a broad range of tumors, including lung, testicular, and germ cell tumors and non-Hodgkin’s lymphoma. Side effects include myelosuppression, hypersensitivity reactions, and alopecia.

imatinib mesylate (Gleevec).
This inhibitor of tyrosine kinase is used primarily to treat chronic myelogenous leukemia. Side effects include neutropenia, hepatotoxicity, and fluid retention.

irinotecan hydrochloride (Camptosar, CPT-11).
Originally isolated from the bark and wood of the Chinese tree Camptotheca accuminata, this agent inhibits the unwinding of DNA and is used in the treatment of GI, cervical, and lung cancers. Side effects include neutropenia, diarrhea, fever, and cardiovascular toxicity.

pegaspargase (Oncaspar).
A conjugated asparaginase, pegaspargase is used in the treatment of childhood acute lymphocytic leukemia. Side effects include hypotension, cough, epistaxis, malaise, nausea, and vomiting.

topotecan (Hycamtin).

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Topotecan is similar to irinotecan in mechanism of action and side-effect profile. It is used most commonly in the treatment of ovarian cancer and small cell lung cancer. Diarrhea is less prominent when using this agent, but some patients develop a flulike syndrome on the first day of therapy.

IMMUNOMODULATING AGENTS IN CANCER
In the 1950s when it was discovered that there was an interference phenomenon between viruses (subsequently labeled “virus-inhibitory factor”), there was no recognition that the scientists had stumbled on one of the arsenals of the body’s own defense mechanism. This interference substance, later called interferon, was found to be produced by leukocytes (white blood cells), and it showed antitumor effects in tissue cultures and animal experiments. A newer form of cancer treatment has come into use with the development of interferons via recombinant DNA techniques—techniques in which a cell or organism receives genes from different parental strains.

aldesleukin (Proleukin).
This human recombinant interleukin is used to treat metastatic renal cell carcinoma and metastatic melanoma in adults. Side effects include flu symptoms, hypotension, ventricular tachycardia, cardiac tamponade, renal failure, toxic psychosis, and GI bleeding.

interferon alfa (Alferon N, Intron A, Rebetron, Roferon-A).
Interferon alfa is actually a family of proteins that possess complex antiviral, antineoplastic, and immunomodulating activities. Interferons for human use are of human origin, produced by means of cultured cells or recombinant techniques. When used in cancer therapy, interferons have a growth-inhibiting effect on normal and malignant cells. Interferon alfa-2a and alfa-2b have been used in the treatment of hairy cell leukemia; Kaposi’s sarcoma in patients with AIDS; renal cell carcinoma; bladder, cervical, and ovarian cancer; melanoma; and multiple myeloma. Interferon alfa is used after surgical resection of melanoma. Side effects include a flulike syndrome, myalgia, arthralgia, anorexia, mental disturbances, elevated liver enzymes, and skin rashes.

docetaxel (Taxotere).
This synthetic derivative of paclitaxel is effective in many tumor types, including breast, lung, esophageal, gastric, head and neck, ovarian, bladder, and testicular cancers. Side effects include neurotoxicity, bone marrow suppression, fluid retention, hypersensitivity reactions, alopecia, and rash.

hydroxyurea, USP-NF, BP (Hydrea).
This derivative of urea is an antineoplastic drug believed to act by interfering in the formation of DNA. Hydroxyurea is used orally in the treatment of essential thrombocytosis, polycythemia vera, and leukemias. In lower doses, it has been used in patients with sickle cell disease to reduce the number of crises. Side effects are bone

MOLECULAR AND TARGETED THERAPIES
Continuing studies aimed at bringing treatment to the cellular level have produced many advances in cancer therapy. Treatment using agents developed through the techniques of molecular medicine and targeted therapy is often more specific for a certain type of cancer than is the case with the other classes of antineoplastic agents.

PLATINUM-CONTAINING AGENTS
Platinum-containing agents exert their effect by binding elemental platinum to DNA and proteins, disrupting their function.

VACCINES USED IN THE TREATMENT OR PREVENTION OF CANCER

human papillomavirus vaccine (Gardasil).
Gardasil is discussed in Chapter 20. It is used to immunize young women against human papillomavirus, the causative agent of cervical cancer.
Dosage: Children and young adults 9 to 26 years: (IM) 0.5 mL in a series of three injections. The second and third injections are administered 2 months and 6 months after the first.

sipuleucel-T (Provenge).
This vaccine is given for metastatic prostate cancer. The patient’s own mononuclear cells are removed through plasmapheresis; activated by exposure to a protein, which consists of prostatic acid fused to a granulocyte-macrophage colony-stimulating factor (GM-CSF); and administered back to the patient.
Dosage: Adults: (IV) Up to 50 million total cells administered back to the patient at 2-week intervals for three doses.

MISCELLANEOUS CANCER TREATMENT AGENTS
The following agents have many different modes of action, and many do not fit into the previously mentioned classes.

docetaxel (Taxotere).
This synthetic derivative of paclitaxel is effective in many tumor types, including breast, lung, esophageal, gastric, head and neck, ovarian, bladder, and testicular cancers. Side effects include neurotoxicity, bone marrow suppression, fluid retention, hypersensitivity reactions, alopecia, and rash.
Dosage: Adults only: (IV) 60 to 100 mg/m2 every 3 weeks.

hydroxyurea, USP-NF, BP (Hydrea).
This derivative of urea is an antineoplastic drug believed to act by interfering in the formation of DNA. Hydroxyurea is used orally in the treatment of essential thrombocytosis, polycythemia vera, and leukemias. In lower doses, it has been used in patients with sickle cell disease to reduce the number of crises. Side effects are bone marrow suppression, nausea, vomiting, diarrhea, lower extremity ulcers, and teratogenicity.
Dosage: Adults: (Oral) 20 to 30 mg/kg daily. Children: Dosage has not been established.

mitotane, USP-NF, BP (Lysodren).
Mitotane is believed to suppress the adrenal cortex and alter the use of steroids. It is used to treat adrenocortical carcinoma. GI disturbances, somnolence, dizziness, anorexia, nausea, vomiting, and diarrhea have occurred after administration.
Dosage: Adults only: (Oral) 2 to 10 gm daily in three or four divided doses.

paclitaxel (Taxol).
Paclitaxel, isolated from the bark of the Pacific yew tree, works by inhibiting cell division. It is used in the treatment of ovarian, breast, lung, head and neck, esophageal, gastric, and bladder cancers. Side effects include bone marrow suppression, acute hypersensitivity reactions, alopecia, neuropathy, cardiotoxicity with bradycardia, and nail bed deformity. Dosage: Adults only: (IV) 135 to 175 mg/m2 every 3 weeks.

paclitaxel nanoparticle albumin (Abraxane, nabpaclitaxel).
Nab-paclitaxel is an albumin-bound version of paclitaxel with the same mechanism of action and side effects. The albumin-bound form gives this drug more specificity for the tumor cells than normal cells. It is used in the treatment of breast cancer after previous treatment failure. Dosage: Adults only: (IV) 100 to 150 mg/m2 weekly 3 out of 4 weeks.

vinblastine sulfate, USP-NF, BP (Velban).
A derivative of the periwinkle plant, this drug acts primarily by interfering with cell division. It is also administered intravenously and has been used with limited success in the treatment of Hodgkin’s disease, lymphosarcoma, and choriocarcinoma. It is of no practical value in the treatment of leukemias. Side effects include bone marrow suppression, neurologic symptoms, alopecia, vomiting, diarrhea, and abdominal pain.
Dosage: Adults: (IV) 4 to 20 mg/m2 weekly. Children: (IV) 2.5 mg/m2 every 1 to 2 weeks.

vincristine sulfate, USP-NF, BP (Oncovin).
Also a derivative of the periwinkle plant, vincristine acts by interfering with normal cellular division. It must be administered intravenously and is used in the treatment of acute lymphocytic leukemia, lymphomas, myeloma, sarcomas, and Wilms’ tumors. Side effects include bone marrow suppression, neurologic symptoms, vomiting, diarrhea, and abdominal pain.
Dosage: Adults: (IV) 0.5 to 1.4 mg/m2 weekly. Children: (IV) 1.5 to 2 mg/m2 weekly.

vinorelbine (Navelbine).
This semisynthetic derivative of vinblastine is active in many tumor types, including breast, lung, head and neck, and ovarian cancers and Hodgkin’s lymphoma. Side effects include bone marrow suppression, nausea, vomiting, diarrhea, alopecia, and abdominal pain.
Dosage: Adults only: (IV) 30 mg/m2 weekly.

SUPPORTIVE AGENTS
Supportive agents are used to make the patient more comfortable during chemotherapy. This may include treating anemia, controlling nausea associated with chemotherapy, and stimulating the appetite in some cases to ameliorate the weight loss associated with cancer and its treatment. IV iron may be used to treat anemia, and blood transfusions are given when appropriate.

HEMATINIC AGENTS

darbepoetin alfa (Aranesp).
This is a long-acting form of epoetin alfa that may be given on an every-2-week protocol. Side effects and uses are the same as the parent compound. It is used to treat chemotherapy-induced anemia. Dosage: Adults only: (Subcut) 200 mcg every 2 weeks.

epoetin alfa (Epogen, Procrit).
Epoetin alfa is a biosynthetic form of the hormone erythropoietin. It is used to treat chemotherapy-induced anemia. In some circumstances, it is also used to treat anemia associated with chronic renal failure, hemodialysis, and other conditions such as HIV infection. There is some potential for abuse by athletes, who may use it to increase the oxygen-carrying ability of cells. Side effects include hypertension, seizures, nausea, cardiovascular incidents, vomiting, and increased incidence of blood clots. There is some evidence that this agent may increase mortality in certain cases; its use should be monitored.

pegfilgrastim (Neulasta).
Filgrastim stimulates the formation of white blood cell precursors in the bone marrow. It is given starting the day after chemotherapy and continued on a daily basis for 7 to 10 days to reduce the chances of neutropenia. It may be used to stimulate stem cell production in donors for bone marrow transplants. Side effects consist mainly of bone pain.

sargramostim (GM-CSF, Leukine).
This agent has the same uses and side effects as filgrastim. Dosage: Adults only: (Subcut) 250 mcg/m2 /da

ANTIEMETICS USED WITH CHEMOTHERAPY
Some routine antiemetics, such as prochlorperazine maleate (Compazine), promethazine (Phenergan), and scopolamine transdermal, may be used when they are sufficient. Generally, more powerful antiemetics are required before and during chemotherapy treatments. These agents generally act centrally through the CNS
by antagonizing serotonin receptors. All doses are for adults. Some agents may be adapted for pediatric use.

aprepitant (Emend)
Dosage: (Oral) 125 mg l hour before chemotherapy, then 80 mg daily for 2 days.

Asperheim, Mary Kaye; Justin Favaro. Introduction to Pharmacology (Page 209). Elsevier Health Sciences. Kindle Edition.

dolasetron (Anzemet)
Dosage: (IV) 1.8 mg/kg before chemotherapy.

dronabinol (Marinol)
Dosage: (Oral) 2.5 mg every 12 hours as needed, maximum 20 mg/day.

granisetron (Kytril) .
Dosage: (Oral) 1 mg every 12 hours for two doses; (IV) Before chemotherapy, an IV infusion of 10 mcg/kg is given as a 5-minute infusion. Dose is given 30 minutes before chemotherapy

granisetron transdermal (Sancuso) .
Dosage: (Transdermal) Each 24-hour patch has 3.1 mg of granisetron. Start 24 hours before chemotherapy; leave in place at least 24 hours after chemotherapy is completed

ondansetron (Zofran)
Dosage: (IV) 32 mg before chemotherapy, or (Oral) 4-8 mg every 6 to 8 hours as needed for nausea.

palonosetron (Aloxi)
Dosage: (Oral) 0.5 mg or (IV) 0.25 mg before chemotherapy.

APPETITE AND ENERGY STIMULANTS FOR CANCER PATIENTS
Appetite and energy stimulants often improve the quality of life for cancer patients. They are meant to counteract the malaise, weight loss, and anorexia that accompany serious illnesses.

dronabinol (Marinol).
This synthetic cannabinoid is derived from marijuana. It is used to treat anorexia associated with cancer conditions. It also relieves nausea and vomiting. Dosage: Adults only: (Oral) 2.5 mg every 12 hours, maximum 20 mg/day.

dexamethasone (Decadron).
This synthetic corticosteroid is used to stimulate the appetite. Side effects of cushingoid syndrome apply. Dosage: Adults only: (Oral) 0.75 mg given Monday, Wednesday, and Friday; may increase as necessary.

megestrol acetate (Megace).
This synthetic progestin may be used to treat anorexia and weight loss in cancer patients and patients with AIDS. Dosage: Adults only: (Oral) 800 mg daily in a suspension.

methylphenidate (Ritalin).
This CNS stimulant is used to improve the patient’s sense of well-being. Dosage: Adults only: (Oral) Up to 10 mg twice daily.

Clinical Implications
1. Patients receiving antineoplastic agents are often anxious and upset. Efforts should be made to provide emotional support to patients and their families.
2. The health care provider should instruct the patient about the importance of good nutrition and his or her nutritional requirements. A diet high in protein but low in saturated fat is optimal (e.g., fish, lean poultry, eggs, nonfat dairy products, nuts, seeds, and legumes). Healthy choices include whole legumes, fruits, and vegetables. Dietary supplements may be beneficial but cannot replace a nutrient-rich diet.
3. Assess the patient’s understanding of his or her illness and the possible side effects of medication.
4. Hair loss can be an emotional issue. Patients should be advised that hair grows back in time, even if total alopecia results from the treatments. A wig purchased in advance is a good idea.
5. Oral lesions and bleeding from the gums may result from treatment with antineoplastic agents. Good oral hygiene should be promoted, such as the use of lemon-glycerin swabs and the avoidance of irritating foods or acidic juices. Ice chips held in the mouth during chemotherapy administration can dilute these drugs in the oropharynx and decrease mucositis and the metallic aftertaste.
6. Common side effects of antineoplastic agents are fever, sore throat, blood dyscrasias, and infections. Patients should be monitored for these effects. Any fever should be reported to the physician immediately.
7. Patients receiving antineoplastic medications are susceptible to untoward effects from minor illnesses. Patients and families should be counseled about avoiding contact with possibly infected persons.
8. Sedation or antiemetic medication before the administration of intravenous agents may minimize the nausea and vomiting produced as side effects. Administration in the evening may allow remission of the nausea before the next morning. Patients should be encouraged to eat small, frequent meals.
9. The site of injection should be observed carefully for signs of extravasation because these agents may produce sloughing of tissues.
10. Observe patients for therapeutic effects, such as reduction in tumor size and weight gain.
11. A patient may be depressed as a result of having cancer. Observation for depression and recommendation for treatment, if indicated, help in the overall management of the patient.

Other Miscellaneous Drugs for the Treatment of Cancer

1. Neoplasms are caused by:
uncontrolled cell division.

2. An antimetabolite, when used to treat cancer, works by:
interfering with some phase of normal cellular metabolism
Interfere with some phase of normal cellular metabolism. Antimetabolites are substances that compete with, replace, or antagonize a metabolic or bodily function.

3. An example of an antimetabolite is
methotrexate.

4. An example of an antiandrogen is:
bicalutamide (Casodex). Generally, this agent is used in combination therapy for the treatment of metastatic cancer of the prostate. Side effects include hot flashes, loss of libido, impotence, gynecomastia, galactorrhea, GI symptoms, and occasionally elevation of the liver enzymes.

5. Androgens may be used to treat:
breast cancer.

6. An example of an antitumor antibiotic is:
dactinomycin.

7. Interferon alfa may be used to treat:
melanoma.
Have been used in the treatment of hairy cell leukemia; Kaposi’s sarcoma in patients with AIDS; renal cell carcinoma; bladder, cervical, and ovarian cancer; melanoma; and multiple myeloma. Interferon alfa is used after surgical resection of melanoma. Side effects include a flulike syndrome, myalgia, arthralgia, anorexia, mental disturbances, elevated liver enzymes, and skin rashes.

8. An enzyme that is used in cancer chemotherapy is:
asparaginase, L-asparaginase (Elspar).
This enzyme, derived from Escherichia coli, is mainly used in combination chemotherapy for childhood acute lymphocytic leukemia, but it is used in adults as well.

9. Hydroxyurea is believed to function in cancer therapy by:
This derivative of urea is an antineoplastic drug believed to act by interfering in the formation of DNA. Hydroxyurea is used orally in the treatment of essential thrombocytosis, polycythemia vera, and leukemias. In lower doses, it has been used in patients with sickle cell disease to reduce the number of crises.

10. An agent used to treat anemia that often occurs after chemotherapy is:
epoetin alfa.

1. Chlorambucil is useful in the treatment of leukemia:
Because it acts on the blood-forming tissues.

2. Drugs like methotrexate that work by interfering with the formation of active folic acid in the body are called:
Folic acid antagonist agents.
In pharmacology, an antagonist agent blocks or interferes with some activity. Methotrexate is called a folic acid antagonist agent because it interferes with the formation of the active form of folic acid.

3. Which of the following types of antineoplastic drug is most likely to antagonize tumors of the reproductive system?
Hormones
Because the reproductive system is greatly affected by hormones, they may be useful in antagonizing tumors of that system.

4. What is the reason that patients on chemotherapy may be given filgrastim (Neupogen)?
To reduce the risk of neutropenia.
Many types of chemotherapy reduce the production of white blood cells (WBCs). Because filgrastim stimulates the formation of WBC precursors in the bone marrow, it is given to reduce the risk of neutropenia in patients on chemotherapy.

5. After the administration of cyclophosphamide (Cytoxan) for the treatment of Wilms tumor, the patient is instructed to observe the urine for signs of bleeding because:
Hemorrhagic cystitis is an adverse effect of cyclophosphamide.
Hemorrhagic cystitis is an adverse effect of cyclophosphamide; therefore the patient should be monitored for bloody urine.

6. Which agent is similar to the body’s own defense mechanism and is effective against cancer cells and viruses?
Interferon-alfa
The activity of pharmacologic interferon is like that of substances produced by WBCs. It has antineoplastic, antiviral, and immunomodulary properties.

7. If a drug is given intrathecally, where is it administered?
Within the spinal cord.
Intrathecal means within the spinal cord, specifically into the subarachnoid space.

8. What is the rationale for giving a patient ice chips to hold in the mouth during chemotherapy administration?
To decrease the risk of mucositis
Mucositis (inflammation of the oral tissues) is a common adverse effect of many antineoplastic agents. Cooling the mouth with ice chips may constrict blood vessels in the mouth, thereby decreasing the exposure of the oral tissues to the drug.

9. Which of the following are common side effects of antineoplastic drugs? Select all that apply.
Anemia, Mouth ulcers, and Erosion of the gastric mucosa.
Anemia may occur because of the drug effects on the bone marrow. Mouth ulcers and gastric ulcers can develop because of the effects of antineoplastic drugs on the gastrointestinal lining. Slurred speech is not a common side effect.

10. Which of the following teaching points are appropriate for the patient receiving antineoplastic drugs? Select all that apply.
Hair will grow back after the treatments are completed.
Avoid people with infections because your resistance is low.
A high-protein, low-saturated fat diet is recommended.

1.What is the difference between the activity of an alkylating agent and an antimetabolite agent?
Alkylating agents attach alkyl groups to the proteins of a cell, thus poisoning it; antimetabolite agents interfere with a phase of cellular metabolism.

2.What is a serious side effect of carmustine (BiCNU)?
A serious side effect of carmustine (BiCNU) is cumulative and delayed bone marrow toxicity that usually occurs 4 to 6 weeks after therapy. Other side effects include nausea, vomiting, renal toxicity, hepatotoxicity, and skin rashes.

3.What is the mechanism of action of cytarabine (Cytosar)?
It is an antimetabolite agent that appears to interfere with DNA formation.

4.What are the side effects of corticosteroid agents when used to treat cancers?
The side effects of corticosteroid agents are salt and water retention, moon facies, edema, and striae.

5.What is the mechanism of action of bleomycin? What type of cancer does it treat?
The antibiotic action of bleomycin appears to occur by causing a splitting of the DNA chain. It is used in the treatment of Hodgkin disease and squamous cell carcinomas of the skin, penis, vulva, head, neck, and larynx.

6.What parts of the body do the major side effects of doxorubicin affect?
The major side effects of doxorubicin affect the bone marrow and the gastrointestinal tract. Cardiotoxicity occurs as well.

7.Which two antitumor antibiotic agents are produced by a strain of Streptomyces, the same microorganism that produces the antibiotic streptomycin?
Doxorubicin and dactinomycin, USP-NF, BP (Actinomycin D, Cosmegen). Doxorubicin and streptozocin are produced by a strain of Streptomyces

8.What are the side effects of interferon-alfa?
Flulike syndrome, myalgia, arthralgia, anorexia, mental disturbances, elevated liver enzymes, and skin rashes are side effects of interferon-alfa.

Side effects include a flulike syndrome, myalgia, arthralgia, anorexia, mental disturbances, elevated liver enzymes, and skin rashes.

9.Name an antiandrogen agent. What condition is it used to treat?
Nilutamide (Nilandron) is an antiandrogen agent used to treat metastatic prostate cancer.

10.What are aromatase inhibitor agents? What are they used to treat?
Aromatase inhibitor agents interfere with estrogen production and can lead to diminished tumor growth. They are used to treat advanced breast cancer in postmenopausal women or may be given after surgical removal of the tumor.

11.What side effects may be a complaint in women who are taking aromatase inhibitor agents?
Side effects of aromatase inhibitor agents are menopausal symptoms such as hot flashes, weight gain, mood changes, osteoporosis, and fractures.

12.What antineoplastic agents are synthetic analogs of the gonadotropin-releasing hormone?
Goserelin acetate, leuprolide acetate, and triptorelin pamoate are synthetic analogs of the gonadotropin-releasing hormone.

13.What may be the side effects of idarubicin hydrochloride?
Side effects of idarubicin hydrochloride are tissue necrosis, myocardial toxicity, nausea, vomiting, and peripheral neuropathy.

1. A child is undergoing treatment for acute lymphocytic leukemia and is presently receiving methotrexate. She has noticed that her long hair is falling out rapidly and is very upset. What would you say to her?
1. Hair loss is a common side effect of antineoplastic drugs, but regrowth occurs when the drug is stopped. A wig is a possible solution in the meantime.

2. A patient is receiving therapy with multiple antineoplastic agents for metastatic breast carcinoma. She has been resisting all attempts to brush her teeth because of extreme soreness in her mouth and throat. What nursing procedures may make her more comfortable?
2. Mouthwashes, cotton applicators with mouth wash, or a Waterpik may be used to gently cleanse the mouth and teeth.

3. A patient is in the office for a follow-up examination after treatment of a brain tumor with carmustine. He asks for a suggestion for a lotion to treat the rash that has appeared on his stomach and thighs. He had been putting Calamine lotion on the rash to no avail.
3. Purpura, which is subcutaneous bleeding, is a significant side effect of these drugs and should be reported to the physician. It may mean that a blood dyscrasia is occurring.

4. A patient is improving with antineoplastic agents but has become more and more quiet and listless. What may be the problem? What suggestions may be made?
4. Anemia should be suspected and may be treated with epoetin alfa. Depression is a common comorbid condition as well, and it should not be ignored. Many patients with serious illnesses could benefit from an antidepressant agent.

1. Alkylating agents attach alkyl groups to the proteins of a cell, thus poisoning it; antimetabolite agents interfere with a phase of cellular metabolism.

2. A serious side effect of carmustine (BiCNU) is 2. cumulative and delayed bone marrow toxicity that usually occurs 4 to 6 weeks after therapy. Other side effects include nausea, vomiting, renal toxicity, hepatotoxicity, and skin rashes

3. A serious side effect of carmustine (BiCNU) is cumulative and delayed bone marrow toxicity that usually occurs 4 to 6 weeks after therapy. Other side effects include nausea, vomiting, renal toxicity, hepatotoxicity, and skin rashes.

4. The side effects of corticosteroid agents are salt and water retention, moon facies, edema, and striae

5. The antibiotic action of bleomycin appears to occur by causing a splitting of the DNA chain. It is used in the treatment of Hodgkin disease and squamous cell carcinomas of the skin, penis, vulva, head, neck, and larynx.

6. The major side effects of doxorubicin affect the bone marrow and the gastrointestinal tract. Cardiotoxicity occurs as well.

7. Doxorubicin and streptozocin are produced by a strain of Streptomyces.

8. Flulike syndrome, myalgia, arthralgia, anorexia, mental disturbances, elevated liver enzymes, and skin rashes are side effects of interferon-alfa.

9. Nilutamide (Nilandron) is an antiandrogen agent used to treat metastatic prostate cancer.

10. Aromatase inhibitor agents interfere with estrogen production and can lead to diminished tumor growth. They are used to treat advanced breast cancer in postmenopausal women or may be given after surgical removal of the tumor.

11. Side effects of aromatase inhibitor agents are menopausal symptoms such as hot flashes, weight gain, mood changes, osteoporosis, and fractures.

12. Goserelin acetate, leuprolide acetate, and triptorelin pamoate are synthetic analogs of the gonadotropin-releasing hormone.

13. Side effects of idarubicin hydrochloride are tissue necrosis, myocardial toxicity, nausea, vomiting, and peripheral neuropathy.

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