week 6: Ch. 57 [Neoplasia] Flashcards
_________________ agents kill or stop the growth of cancer cells & may be classified as:
–Alkylating agents
–Antimetabolites
–Antitumor antibiotics
–Hormones and hormone antagonists
–Natural products
–Biologic response modifiers and targeted therapies
–Miscellaneous antineoplastic drugs
Antineoplastic
Antineoplastic agents kill or stop the growth of :
cancer cells
Alkylating Agents
- Alter the shape of the : 1
- Prevent DNA from : 2
- Kill cancer cells when : 3
- Suppress : 4
(myelosuppression) - Damage epithelial cells
1- DNA double helix
2- duplicating
3- they divide
4- bone marrow
Alkylating Agents can lead to :
- Alopecia
- Strong vesicants [blistering]
- Secondary malignancies
- Can develop resistance
Prototype drug for Alkylating Agents :
Cyclophosphamide (Cytoxan)
Prototype drug: Cyclophosphamide (Cytoxan)
Adverse effects:
anorexia, nausea, vomiting, weight loss, diarrhea, and mouth sores
–Alopecia occurs in 50% of patients
– jaundice, acne, blistered skin, darkened or thickened skin
▪Serious adverse effects
–Bone marrow suppression
–Severe infection and sepsis
– Cardiotoxicity
–Pulmonary fibrosis
– Hematuria may signal hemorrhagic cystitis
– Interfere w/ ability to reproduce
– Risk of secondary malignancies
Prototype drug: Cyclophosphamide (Cytoxan)
– Therapeutic classification ?
– Pharmacologic classification ?
Therapeutic classification
▪Antineoplastic
Pharmacologic classification
▪Alkylating agent, nitrogen mustard, disease-modifying antirheumatic drug, immunosuppressant
Therapeutic effects and uses of Cyclophosphamide (Cytoxan)
▪Cancers of ____________________
– Chemo of Hodgkin’s & non- Hodgkin’s lymphoma
– Acute & chronic lymphocytic & myelogenous leukemia
▪Ovarian & _________ cancer
▪Multiple myeloma
▪Mycosis fungoides
▪Neuroblastoma
▪Sarcomas
▪Retinoblastoma
▪Off-label uses = other cancers
▪Cancers of the lymph nodes
– Chemo of Hodgkin’s & non- Hodgkin’s lymphoma
– Acute & chronic lymphocytic & myelogenous leukemia
▪Ovarian & breast cancer
▪Multiple myeloma
▪Mycosis fungoides
▪Neuroblastoma
▪Sarcomas
▪Retinoblastoma
▪Off-label uses = other cancers
Cyclophosphamide (Cytoxan)
– Mechanism of action
▪Converted to its active form (phosphoramide mustard) in ______________
▪Binds to DNA and forms cross-links
–Prevent the synthesis of______________________________
▪It is a cell cycle nonspecific drug.
▪Converted to its active form (phosphoramide mustard) in the liver
▪Binds to DNA and forms cross-links
–Prevent the synthesis of DNA, RNA, & protein
▪It is a cell cycle nonspecific drug.
Cyclophosphamide (Cytoxan)
– Contraindications/precautions
▪Pregnancy & lactation
▪Severe myelosuppression
▪Leukopenia
▪Thrombocytopenia
▪Previous radiation therapy
▪Bone marrow infiltration of tumor cells
▪Chronic kidney disease (CKD)
▪Impaired hepatic function
▪Recent history of steroid use
▪Previous therapy that caused cytotoxicity
Cyclophosphamide (Cytoxan)
– Drug interactions
▪Many drug interactions possible due to its extensive hepatic metabolism.
▪Additive immunosuppressive effects if taken with other agents that cause bone marrow toxicity
▪May be an increased anticoagulant effect if given with anticoagulants
▪Increased cardiotoxicity may result if given with doxorubicin
▪Insulin may increase hypoglycemia.
▪Lower serum digoxin levels in patients who takes digoxin
▪Phenobarbital use may lead to increased rate of metabolism
▪Phenytoin use may lead to an increased risk of toxicity.
– Herbal/Food
▪St. John’s wort may increase toxic effects.
Cyclophosphamide (Cytoxan) – Treatment of overdose
▪General supportive measures for severe myelosuppression with the possibility of infection
Antimetabolites are similar structured to nutrients required by:
rapidly growing cancer cells
Antimetabolites disrupt _________ ____________ of cancer cells
metabolic pathways
Antimetabolites inhibit __________ and are cell cycle specific
enzymes
Antimetabolites
Prototype drug:
Methotrexate (MTX, Rheumatrex, Trexall)
Methotrexate (MTX, Rheumatrex, Trexall)
– Therapeutic classification ?
– Pharmacologic classification ?
Therapeutic classification
▪Antineoplastic
Pharmacologic classification
▪Antimetabolite, folic acid analog,
immunosuppressant, disease-modifying antirheumatic drug (DMARD)
Methotrexate (MTX, Rheumatrex, Trexall)
– Therapeutic effects and uses
▪Neoplastic conditions, including osteosarcoma
▪Acute lymphocytic and
lymphoblastic leukemias
▪Lymphosarcoma in children
▪Certain inoperable head, neck, and pelvic cancers
▪Breast & Lung cancer
▪Advanced-stage non-Hodgkin’s lymphoma
▪Combo therapy to maintain remissions after surgical resection of a primary tumor
▪Powerful immunosuppressant
Methotrexate (MTX, Rheumatrex, Trexall)
– Mechanism of action
▪Specific for ___ _______ of the cell cycle
▪It blocks an enzyme that is responsible for
_________________________________________, which
interferes with DNA synthesis, repair, and cellular
replication mainly in actively proliferating tissues.
▪This action enables it to be effective in treating
_________________________________ in addition to cancer.
▪Specific for S phase of the cell cycle
▪It blocks an enzyme that is responsible for
converting folic acid to reduced folate, which
interferes with DNA synthesis, repair, and cellular
replication mainly in actively proliferating tissues.
▪This action enables it to be effective in treating
psoriasis and arthritis in addition to cancer.
Methotrexate (MTX, Rheumatrex, Trexall)
– Adverse effects/ black box warning
– Adverse effects
▪Nausea and vomiting are severe at high doses.
▪Serious adverse effects
– Uric acid nephropathy
– GI hemorrhage
– Hemorrhagic enteritis
–Pancreatitis
–Pericardial effusion
–Pulmonary embolism
– Black box warnings
▪Methotrexate combined with NSAIDs may cause
severe/fatal myelosuppression
▪Hepatotoxic
▪Ulcerative stomatitis & diarrhea may lead to
hemorrhagic enteritis & death from intestinal
perforation.
▪Pneumocystis pneumonia
▪Pulmonary toxicity may result in acute or chronic
interstitial pneumonitis at any dose level.
▪Severe, sometimes fatal, dermatologic reactions
Methotrexate (MTX, Rheumatrex, Trexall)
– Contraindications/precautions
▪Thrombocytopenia
▪Anemia, Leukopenia
▪Concurrent administration of hepatotoxic drugs
and hematopoietic suppressants
▪Alcoholism
▪Lactation
▪CKD
▪Impaired hepatic function
▪Active infections
▪Ulcerative colitis, Peptic ulcers
▪Patients with cancer who have preexisting bone
marrow impairment
▪Patients who are very young, older, or debilitated
▪poor nutritional status
▪Confirmed teratogen; avoid pregnancy during
therapy
▪caution in handling; can cause severe skin
reactions
▪Interacts with many drugs
▪Increased serum methotrexate levels can occur with the penicillins, vancomycin, cyclosporine, and para-amino benzoic acid.
▪Chloramphenicol may decrease intestinal absorption.
▪Increased effect can occur with probenecid, ibuprofen, aspirin, and tetracyclines
▪Folic acid may alter the body’s response to
methotrexate
▪Can cause decreased phenytoin effects
▪Immunization during therapy is not effective.
▪Any live vaccine use may lead to a severe
reaction secondary to the immunosuppressant
activity of methotrexate
– Herbal/Food
▪Food delays oral absorption.
▪Echinacea may increase risk of hepatotoxicity.
▪More than 180 mg/day of caffeine may decrease
effectiveness of methotrexate when taken for
arthritis
Methotrexate (MTX, Rheumatrex, Trexall)
– Treatment of overdose
▪_______________ or levoleucovorin as soon as possible
▪In some cases, leucovorin is given 24 to 36 hours after methotrexate chemotherapy to “rescue” normal cells.
▪Leucovorin or levoleucovorin as soon as possible
▪In some cases, leucovorin is given 24 to 36 hours after methotrexate chemotherapy to “rescue” normal cells.
methotrexate (MTX, Rheumatrex, Trexall)
– Nursing responsibilities
▪Monitor: 1
▪Be alert for and report symptoms of: 2
1- I&O ratio and pattern
2- thrombocytopenia
Antitumor Antibiotics bind to:
DNA
- Mechanism of action similar to alkylating agents
Antitumor Antibiotics contain substances obtained from bacteria that can:
kill cancer cells
Antitumor Antibiotics: their use is restricted to treating
a few specific types of cancer
Antitumor Antibiotics
how are they given?
IV or direct instillation via catheter
Antitumor Antibiotics
a great risk is:
bone marrow supression
[myelosuppresion]
Antitumor Antibiotics can cause major damage to the skin, subcutaneous tissue, and nerves should __________ occur
extravasion
Antitumor Antibiotics
Prototype drug: Doxorubicin (Adriamycin)
– Therapeutic classification ?
– Pharmacologic classification ?
Therapeutic classification
▪Antineoplastic
Pharmacologic classification
▪Antitumor antibiotic, anthracycline
Doxorubicin (Adriamycin)
– Therapeutic effects and uses:
▪Treat neuroblastoma and____________________ of the bone, bladder, breast, ovary, GI tract, lung, & thyroid
▪Part of many ______________ regimens for other tumors
▪Effective as a pre-radiation therapy to sensitize superficial tumors
▪Treat neuroblastoma and solid tumors of the bone, bladder, breast, ovary, GI tract, lung, & thyroid
▪Part of many chemotherapy regimens for other tumors
▪Effective as a pre-radiation therapy to sensitize superficial tumors
Doxorubicin (Adriamycin)
– Mechanism of action’
▪Binds to DNA, causing:
▪It is cell cycle:
▪Binds to DNA, causing strand splitting and inhibition of DNA synthesis
▪It is cell cycle nonspecific
Doxorubicin (Adriamycin)
– Adverse effects
& Black box warnings
▪Severe nausea, vomiting, mucositis, rash, excessive lacrimation, hepatotoxicity, anaphylaxis, complete alopecia, & radiation recall phenomenon
▪Turns urine and tears a red color
▪Temporary decreased fertility likely (M & F)
– Black box warnings
▪Severe myelosuppression may occur.
▪Significant cardiotoxicity
▪Cardiac adverse effects may be life threatening.
▪Heart failure
▪Severe local necrosis
▪Secondary malignancies
Doxorubicin (Adriamycin)
– Contraindications/precautions
▪Pregnancy
▪Lactation
▪Myelosuppression
▪Thrombocytopenia
▪Preexisting cardiac disease
▪Obstructive jaundice
▪Previous treatment with complete cumulative
doses of doxorubicin or daunorubicin
▪CKD
▪Impaired hepatic function
▪History of atopic dermatitis
▪Patients who have received cyclophosphamide or
pelvic radiation therapy to areas surrounding the
heart
Doxorubicin (Adriamycin)
– Drug interactions
▪Increased toxicity may occur with other antineoplastics, radiation therapy, or mercaptopurine.
▪Cyclophosphamide may increase the risk of hemorrhagic cystitis or cardiac toxicity.
▪Paclitaxel may decrease the clearance of doxorubicin.
▪Phenobarbital and other barbiturates increase elimination.
▪Decreased phenytoin levels may occur.
▪Concurrent use with verapamil can raise serum levels.
▪Use with paclitaxel > increased incidence of stomatitis, neutropenia, heart failure.
▪Concurrent use with NSAIDs, anticoagulants, or platelet inhibitors may cause excessive bleeding.
Doxorubicin (Adriamycin)
– Treatment of overdose
▪Antibiotics, platelets, and granulocytes
▪Symptoms of mucositis and heart failure treated symptomatically
Hormones & Hormone Antagonists
they block substances necessary for :
continued tumor growth
Hormones & Hormone Antagonists
Therapy is limited to hormone-sensitive tumors of the :
breast or prostate.
Hormones & Hormone Antagonists are NOT:
cytotoxic
[not toxic to living cells]
Hormones used in treating cancer include:
–Corticosteroids
–Progestins
–Estrogens
–Androgens
Hormones & Hormone Antagonists are usually given for palliative care, meaning
given to reduce symptoms/pain of cancer, not to cure
Hormones & Hormone antagonists
* Prototype drug: Tamoxifen
– Therapeutic classification ?
– Pharmacologic classification ?
Therapeutic classification
▪Antineoplastic
Pharmacologic classification
▪Hormonal agent, estrogen receptor blocker
Tamoxifen
– Therapeutic effects and uses
▪Palliative treatment of advanced, metastatic, ER-positive ________________ in men and postmenopausal women
▪Off-label indications include astrocytoma, malignant glioma, malignant melanoma, and ovarian cancer.
▪Prophylaxis of __________________ in women who have a high risk of developing the disease
▪Adjunctive therapy in women following a mastectomy to decrease the potential for cancer in the contralateral breast
▪Off-label: Treatment of infertility and to reduce pain associated with gynecomastia in women and men
▪Palliative treatment of advanced, metastatic, ER-positive breast cancer in men and postmenopausalwomen
▪Off-label indications include astrocytoma, malignant glioma, malignant melanoma, and ovarian cancer.
▪Prophylaxis of breast cancer in women who have a high risk of developing the disease
▪Adjunctive therapy in women following a mastectomy to decrease the potential for cancer in the contralateral breast
▪Off-label: Treatment of infertility and to reduce pain associated with gynecomastia in women and men
Tamoxifen
– Mechanism of action
▪Binds to _________________, producing agonist effects in some tissues (bone) and antagonist effects in other tissues (breast)
▪The binding in breast tissue inhibits ______ _______________ and affects other growth factors in cancer cells.
▪Binds to Estrogen Receptors (ER), producing agonist effects in some tissues (bone) and antagonist effects in other tissues (breast)
▪The binding in breast tissue inhibits DNA replication and affects other growth factors in cancer cells.
Tamoxifen
– Adverse effects & Black box warning
▪Nausea & vomiting
▪Other common adverse effects:
– Hot flashes, vaginal discharge, irregular menses, vaginal bleeding, fluid retention, headaches, light-headedness, rash
– Black box warnings
▪Increased risk of endometrial cancer
▪Slightly increased risk of thromboembolic disease,
including stroke, pulmonary embolism, and deep
vein thrombosis (DVT)
Tamoxifen
– Contraindications/precautions
▪Contraindications:
–Anticoagulant therapy, preexisting endometrial
hyperplasia, history of thromboembolic disease, pregnancy and lactation
▪Precautions:
– Leukopenia, thrombocytopenia, visual disturbances, cataracts, bone marrow suppression, hypercalcemia, hypercholesterolemia
Tamoxifen
– Drug interactions
▪May interact with inducers or inhibitors of CYP
enzymes
▪Use with warfarin increases risks of bleeding
▪Cytotoxic antineoplastics may increase risk of
thromboembolism.
▪Bromocriptine may increase tamoxifen levels.
▪Aminoglutethimide, medroxyprogesterone, or rifamycin may decrease tamoxifen levels.
▪SSRIs may decrease effectiveness.
▪Should not be used with oral contraceptives
– Herbal/Food
▪Black cohosh should not be taken unless approved by the healthcare provider.
Tamoxifen – Treatment of overdose
Symptomatic for seizures, neurotoxicity, and QT interval changes
[Treating these symptoms of the after-effects / adjusting dose]
Natural products that are derived from ______ are another class of Antineoplastic medication
plants
Natural Products
* Three subdivisions
–Vinca alkaloids = derived from-
–Taxanes = derived from-
–Topoisomerase inhibitors
–Vinca alkaloids = derived from periwinkle plant
–Taxanes = derived from bark of the pacific yew tree
–Topoisomerase inhibitors
Natural products (antineoplastic meds) are able to:
stop cell divison
Natural Products
Vincristine (Marqibo, Oncovin)
– Therapeutic classification ?
– Pharmacologic classification ?
– Therapeutic classification
▪Antineoplastic
– Pharmacologic classification
▪Vinca alkaloid, mitotic inhibitor, natural product
Vincristine (Oncovin)
– Therapeutic effects and uses
▪Acute lymphocytic ____________
▪Hodgkin’s and non-Hodgkin’s ________________
▪Lymphosarcoma
▪Malignant glioma
▪Neuroblastoma
▪Rhabdomyosarcoma
▪Soft tissue sarcoma
▪Wilms’ tumor
▪Off-label for breast, colorectal, and lung cancers
▪Acute lymphocytic leukemia
▪Hodgkin’s and non-Hodgkin’s lymphomas
▪Lymphosarcoma
▪Malignant glioma
▪Neuroblastoma
▪Rhabdomyosarcoma
▪Soft tissue sarcoma
▪Wilms’ tumor
▪Off-label for breast, colorectal, and lung cancers
Vincristine (Oncovin)
– Mechanism of action
▪Binds to ___________, a protein that makes up the _____________ of the cell that are necessary for cell division
▪This disrupts the process whereby chromosomes are distributed to the daughter cells during _________, resulting in:
▪Binds to tubulin, a protein that makes up the microtubules of the cell that are necessary for cell division
▪This disrupts the process whereby chromosomes are distributed to the daughter cells during mitosis, resulting in cell death.
Vincristine (Oncovin)
– Adverse effects & black box warning
▪Neurotoxicity
– Motor difficulties, peripheral neuropathy,
paresthesias (especially of the hands and feet),
weakness, cranial nerve palsies (diplopia,
hoarseness, deafness, trigeminal neuralgia,
vocal cord paralysis), and decreased reflexes
▪CNS effects may include seizures, depression,
hallucinations, and coma.
▪GI: Nausea, vomiting, anorexia, stomatitis, severe
constipation, and abdominal pain.
▪Other adverse reactions include hepatotoxicity,
rash, paralytic ileus (especially in children), and
alopecia.
– Black box warnings
▪Myelosuppression
▪Extravasation
: Vincristine (Oncovin)
– Contraindications/precautions
▪Obstructive jaundice
▪Men and women of childbearing age
▪Active infection
▪Adynamic ileus
▪Radiation of the liver
▪Infants
▪Pregnancy
▪Lactation
– Precautions
▪Patients with leukopenia, preexisting
neuromuscular or neurologic disease,
hypertension, CKD or hepatic impairment
▪Those taking drugs with neurotoxic properties
▪Older adults
▪Reduce doses in patients with hepatic or biliary
disease
▪Avoid exposure of skin to this drug
Vincristine (Oncovin)
– Drug interactions
▪Agents that induce CYP3A4 may increase metabolism of vincristine and decrease effects of the medication.
▪Increases action of methotrexate, bleomycin, and
anticoagulants
▪Decreased digoxin and phenytoin levels will occur.
▪Administration of L-asparaginase just prior to
vincristine will cause additive neurotoxicity.
▪Concurrent administration with mitomycin may cause acute dyspnea and severe bronchospasm.
▪Neurotoxicity may occur with peripheral nervous
system drugs.
Vincristine (Oncovin) – Treatment of overdose
▪No antidote [no specific treatment]
▪Patients treated symptomatically
A biologic response modifier is a substance that enhances the ability of body defenses to:
remove cancer cells
Biologic Response Modifiers and Targeted Therapies
- Two general classes:
cytokines and monoclonal antibodies
Cytokines that act as biologic response modifiers [3]
–Interferons
–Interleukin-2
–Hematopoietic growth factors
Interleukin-2 activates the ____________________________ and promotes other actions of immune response so it can decrease tumor/kill cancer that is growing
cytotoxic T-lymphocyte
Hematopoietic growth factors promote the formation of ___________________________ and these enhance the ability of the immune system to respond and reduce some of the myelosuppression caused by antineoplastic meds
specific blood cells
Targeted therapies
–Drugs that block the :
growth, progression, and spread of cancer
Monoclonal antibodies (MABs) are ____________________________________________
biologic response modifiers
Monoclonal antibodies (MABs)
–Once MAB binds to specific antigen, cancer cell is
either killed by drug or _________________________ by other cells of immune response.
marked for destruction
Monoclonal antibodies (MABs) require that tumor cells possess specific :
protein receptors
Miscellaneous Antineoplastics
*Structurally dissimilar to:
*Each is unique, so:
*Structurally dissimilar to other neoplastics
*Each is unique, so adverse reactions vary.
Antiemetics decrease or prevent:
nausea and vomiting
Drugs for bowel disorders
–Decrease either:
constipation or diarrhea
3 types of drugs used to prevent serious complications of _________________:
–Epoetin alfa (Epogen, Procrit)
–Colony-stimulating factors such as filgrastim (Granix, Neupogen, Zarxio)
–Oprelvekin (Neumega
myelosuppression
A large number of antineoplastic medications are
absorbed through the skin and mucous membranes, so the individual preparing and administering them is at risk for:
absorbing them.
~Nurses/healthcare professionals must wear protective clothing, including gloves, whenever handling them.
~Both the Oncology Nursing Society and OSHA have established and publicized guidelines for safe handling of antineoplastic medications
