Pharmacology- Cancer Drugs

growth fraction

a major determinant of its responsiveness to chemotherapy, the cell cycle should be reviewed

Cell-cycle non-specific drugs

a. Cell-cycle phase-nonspecific drugs can affect cells during any phase of the cell cycle, including G0. b. they usually are, however, more toxic to replicating cells than to cells in G0 → cells that divide more rapidly are more vulnerable as they have less time for repairs than resting cells

Cytotoxic anticancer drugs

are more toxic to cancers that have a high growth fraction than to cancers that have a low growth fraction

Anti-Metabolites (cell-cycle specific, usually S-phase)

are structural analogs of important natural metabolites and are thus able to disrupt critical metabolic processes

Most common cancers in females

breast; lung; colon; rectum

ability to form metastases

built on the above principle of malignant cells ability to break away from the site of origin and implant and grow in sites/organs/tissues that are remote.

killing normal cells

can't kill target cells without

immortality

cancer cells can undergo countless divisions due to the activity of telomerase (anenzyme present in most cancers that is not present in most healthy cells). It permits repeated cell divisions by preserving the telomere protein cap found on the ends of DNA, which keeps adding to the length of the telomeres themselves, thus allowing for continual cell division

invasive growth

cancer don't adhere to the rule that healthy cells follow that dictates that healthy cells don't invade the territory of other non-similar healthy cells

Agents most likely to cause severe N/V

carmustine; cisplatin; high dose cyclophosphamide; dacarbazine; dactinomycin; mechlorathemine; streptozocin

chemicals, viruses, radiation

causes a series of steps in malignant transformation leading to: a. activated oncogenes b. inactivated tumor suppressor genes

hyperuricemia

d/t rapid tumor cell lysis → potential renal failure a. increase fluids b. administer allopurinol (Zyloprim)

Retinoids

derivatives of vitamin A that activate retinoid receptors to regulate the proliferation and differentiation of cells. In cancer patients, they inhibit cancer cell growth.

G0 phase

everyday cellular activities occur (aka "resting phase")

Regional drug delivery

ex: intra-arterial; intra-thecal; portal vein; intra-vesicular (urinary bladder); intra-cavitary (pleural and peritoneal cavities)

acne-like rash with Kinase inhibitors

face and upper torso (88% of patients) and can lead to staph aureus sepsis → exposure to sunlight can exacerbate the reactionso sunblock and protective clothing is essential if sun exposure can't be avoided altogether during therapy

The right dosing schedule

for drugs that act during a specific phase of the cell cycle, selecting what is critical to success of the therapy

raloxifene (Evista)

for post-menopausal women

tamoxifen (Nolvadex

for pre and post-menopausal women

Only some rarer cancers (ex: acute lymphocytic leukemia, Hodgkin's disease, certain testicular cancers)

have a high growth fraction, and therefore tend to respond well.

tissues composed mostly of G0 cells

have a low growth fraction

most common cancers (solid tumors of the breast, lung, prostate, colon, and rectum

have a low growth fraction and therefore respond poorly to drugs

Tissues with a large percentage of proliferating cells and few cells

in G0 have a high growth fraction.

toxicity to normal cells

is dose-limiting

Cancer

is the 2nd leading cause of death - kills about 572,000 people annually (as of 2011) and is the leading cause of mortality in females aged 30-74. Not a single disorder, but rather a large group of disorders that differ with respect to clinical presentation, aggressiveness, drug sensitivity, and prognosis.

neutropenia

look for fever as the sign of infection in this setting because other S/S of infection likely will not be present as they depend on the presence of neutrophils to be initiated (ex: pulmonary infiltrates; pus; abscesses)

persistent proliferation

malignant cells do not respond to the feedback mechanisms that usually regulate cellular proliferation in healthy tissue

M phase

mitosis

Surgery and Radiation

most common for solid tumor removal

drug therapy/chemotherapy

most effective for widespread/disseminated cancers, and as an "adjuvant" therapy for surgery and radiation (kills/suppresses cancer cells left behind by chemotherapy and radiation)

diarrhea

often treated with PO loperamide (Imodium) to slow intestinal motility

G2 phase

pre-mitotic phase (synthesis of components needed for mitosis)

Most common cancers in males

prostate; lung; colon; rectum

Selective Estrogen-receptor Modulators: Drugs for Breast Cancer Prevention in High-Risk Women

raloxifene (Evista) and tamoxifen (Nolvadex)

interstitial lung disease from kinase inhibitors

rare but can be deadly d/t inflammation and scarring of lungs

protein tyrosine kinases

regulate cellular growth, proliferation, and angiogenesis, and mediate signal transmission within human cells

alopecia

see especially with cyclophosphamide, doxorubicin, dactinomycin, bleomycin, paclitaxel, topotecan a. anticipatory counseling → scarves, wigs b. reassurance that hair will grow back

malignant transformation causes quantitative rather than qualitative changes in cellular function

simply results in the overexpression/under-expression of the same gene products made by normal cells. Malignant cells use the same metabolic pathways/ machinery as normal cells, which makes them susceptible to some drugs and treatments

. tyrosine kinase inhibitors (TKI)

small molecules that have been developed to act on tumor and and tumor vasculature, blocking receptor tyrosine kinase activity and pathways that are critical for tumor growth and progression

growth fraction

the ratio of proliferating cells to cells in G0

Anticipatory N/V

treated with benzodiazepines (ex: alprazolam (Xanax); lorazepam (Ativan))

Heterogeneity of tumor cells

tumors can be made of dissimilar cells (sub-populations) that can respond differently to the anti-cancer drugs (↑s with age of the tumor)

Denileukin diftitox

used to treat cutaneous T-cell lymphoma. Can cause severe hypersensitivity reactions and capillary leak syndrome

Thalidomide:

used to treat erythema nodosum leprosum (a complication of leprosy) and multiple myeloma (bone marrow cancer). An extremely powerful teratogen

nadir (lowest neutrophil count)

usually happens 10-14 days after dosing, and usually recovers in about a week; sometimes see a delayed drop

local injury from extravasation of vesicants

very damaging to vessels > esp. doxorubicin and vincristine

→ Sipuleucel-T (Provenge)

→ a patient-specific immunotherapy designed to stimulate an immune attack against prostate cancer cells. Each dose is custom made from the patient's own immune cells, collected by leukopheresis. Very expensive and only moderately effective.

Arsenic trioxide

→ approved to treat a rare sub-type of acute promyelocytic leukemia

→ magnesium supplementation is recommended SE of kinase inhibitors

→ magnesium supplementation is recommended

neutropenia

(Normal range for neutrophils = 2,500-7,000 cells/mm³) < 1,000 cells/mm³ , chemo will usually be delayed if ANC drops below 500

infusion reaction with Kinase inhibitors

(airway obstruction; hypotension; MI; cardiopulmonary arrest) → will typically happen on first infusion if it's going to happen → tx'd with epinephrine, glucocorticoids, IV antihistamines; bronchodilators, ventilator support. Premedication with antihistamine and steroids is recommended

stomatitis

(inflammation of the oral mucosa) caused by cytotoxic drugs

anemia

(normal RBC count: women: 4.2 to 5.4 million/uL; men: 4.7 to 6.1 million/uL), usually peaks 7-14 days after dose, much less common than neutropenia or thrombocytopenia

thrombocytopenia

(normal platelet count = 150,000 - 400,000/microliter [mcL]), usually peaks 7-14 days after dosing

The Cell Cycle

- the sequence of events that a cell undergoes in 1 mitotic division

Angiogenesis inhibitors (example: bevacizumab [Avastin])

. Adverse effects: a. GI perforation b. hemorrhage (lung bleeding) c. thromboembolism d. nephrotic syndrome (monitor for protein in the urine) e. disruption of wound healing (can cause wound dehiscence after surgery) f. hypertensive crisis (assess BP, even months after drug course is completed) 4. Administration: IV infusion

. Solid tumors typically respond poorly to chemotherapy (they have a low growth fraction)

. more cells are in the G0 phase the older they get / the larger they are 2. happens bc cells in the center of a large tumor get less blood flow/nutrients 3. this is why surgical "debulking" of a tumor cn make it more responsive to chemotherapy

Nursing implications for extravasation of vesicants

1) Inject the chemotherapy agent into rapidly flowing IV solution 2) Assess site frequently 3) Stop drug immediately if extravasation occurs and aspirate as much of drug as possible 4) Warm soak with vincristine; cold compress with doxorubicin and then follow institutional protocol 5) Protocols often include the local injection of either hyaluronidase, sodium thiosulfate, or dimethylsulfoxide (DMSO)

non-anthracyclines (ex: dactinomycin [Actinomycin-D])

1) MOA: Very similar to doxorubicin 2) SE: N/V/D; bone marrow suppression; severe vesicant therefore extravasation is a particular concern; hepatotoxicity; sepsis; esophagitis/ulcerative stomatitis 3) Indications: active against many cancers, especially solid tumors and disseminated Cancers. Specific indications include Wilm's tumor; rhabdomyosarcoma; Ewing's sarcoma; Kaposi's sarcoma; testicular cancer 4) Administration: IV infusion; regional perfusion to tumor site 5) Dose-limiting toxicity: bone-marrow suppression; oral/GI mucositis

Purine Analogs (ex: mercaptopurine [Purinethol])

1) MOA: disrupts multiple biochemical processes. Is a "pro-drugs" and must be converted to its active form in the body 2) SE: thrombophlebitis; rash; hyperuricemia; multiple GI eefects; bone marrow suppression 3) indications: acute lymphocytic leukemia 4) administration: oral 5) dose limiting toxicity: bone marrow suppression

anthracyclines (ex: doxorubicin [Adriamycin])

1) MOA: distorts DNA structure thus inhibiting the synthesis of DNA and RNA also forms a complex with an enzyme called topoisomerase to enhance cleaving (cutting up of) DNA and interfering with the natural ability of the enzyme to promote repair of DNA 2) SE: N/V; alopecia; bone marrow suppression; cardiotoxicity; red color to urine and tears; severe vesicant therefore extravasation is a particular concern tx'd with local icepacks and institutional protocol 3) Indications: active against many cancers, especially solid tumors and disseminated cancers Specific indications include lymphomas; sarcomas; carcinomas 4) Administration: IV infusion 5) Dose-limiting toxicity: Bone-marrow suppression (neutropenia in 70% of patients)

. Folic acid analogs (ex: methotrexate [Trexall])

1) MOA: inhibits an enzyme that is essential in the process of activation of folic acid, thus disrupting the cells ability to make DNA → thus it is S-phase specific 2) Special note → leucovorin (folinic acid) rescue can be used to enhance the effects of methotrexate. It bypasses the metabolic block created by methotrexate in the cancer cells thereby allowing normal cells to synthesize the products necessary for folic acid activation and use in the normal cells. Is very risky (can be fatal if timing of administration is wrong) and is only used in select cases where very high doses of methotrexate are needed 3) dose-limiting toxicity: bone marrow suppression; pulmonary infiltrates; GI ulceration → can lead to intestinal perforation and hemorrhage

Pyrimidine Analogs (ex: cytarabine [cytosine arabinoside; Ara-C])

1) MOA: is a base employed in the biosynthesis of DNA and RNA and therefore is used to disrupt DNA and RNA synthesis. Is a "pro-drugs" and must be converted to its active form in the body 2) SE: thrombophlebitis; rash; hyperuricemia; multiple GI effects; bone marrow suppression 3) indications: acute myelogenous leukemia 4) administration: IV, Subcu, intrathecal 5) dose limiting toxicity: bone marrow suppression

carmustine (Gliadel) (prototype for nitrosureas)

1) SE: can cause severe N/V and pulmonary fibrosis 2) used in the brain as an impregnated implantable-wafer after tumor emoval 3) indications → brain tumors (can cross the BBB); hodgkins/non-hodgkins lymphoma; malignant melanoma; hepatoma; adenocarcinoma of GI tract 4) dose-limiting toxicity: delayed bone marrow suppression

Nursing implications for patients with neutropenia

1) Well-balanced high calorie, high protein diet 2) Avoid contact with crowds, fresh flowers/fruits/vegetables, animals, soil 3) Handwashing 4) Good personal hygiene 5) Meticulous care of indwelling IV access devices according to institutional protocol 6) Avoid indwelling urinary catheters if possible 7) Cultures with fever 8) after cultures, initiation of empiric antibiotic therapy (for gram (-) organisms) a) ceftazidine b) imipinem c) doripenem d) an aminoglycoside should sepsis develop (tobramycin; gentamicin; amikacin) e) vancomycin (for gram (+) coverage) if still febrile after the above

paclitaxel (Taxol) (taxane)

1) adverse effects: anaphylaxis and severe hypersensitivity reactions (hypotension; dyspnea; urticaria) 2) indications: first-line therapy (in combo with cisplatin) for advanced ovarian cancer and non-small-cell lung cancer in patients for whom curative surgery or radiation is not possible. 3) administration: a) IV infusion b) requires premedication with steroids and diphenhydramine (Benadryl) 4) dose-limiting toxicity: bone-marrow suppression

Nursing implications for patients with thrombocytopenia

1) assess for bleeding and teach patient to assess for bleeding 2) bleeding from mucus membrane usually occurs first (nose; gums) 3) soft-bristle tooth brush and gentle brushing 4) avoid drugs that cause risk of bleeding (ASA; NSAIDs: warfarin) 5) possible platelet infusion 6) possible administration of oprelvekin (Neumega) for low counts (usually < 20,000) (colony-stimulating factor) 7) hold pressure on venipuncture sites for 5 minutes 8) cautious use of BP cuffs

cyclophosphamide (Cytoxan)(nitrogen mustard)

1) has broad spectrum activity, and is the most widely used alkylating agent 2) most useful in the treatment of slow-growing cancers 3) indications: hodgkins and non-hodgkins lymphomas; multiple myeloma; solid tumors of head, neck, ovary, breast

vincristine (Oncovin) (vinca alkaloid)

1) is bone-marrow sparing and is thus good for combination therapy. Used often in blood and lymph cancers; breast; and bladder 2) administration: IV infusion 3) dose-limiting toxicity: peripheral neuropathy (disrupts neuromicrotubules). Nearly all patients experience symptoms of sensory and motor nerve injury

Nursing implications for patients with anemia

1) well-balanced diet 2) adequate rest 3) adminstration of epoetin-alpha (Epogen) (colony stimulating factor) → typically used when the goal of treatment is palliation as it can shorten the life-expectancy of cancer patients

. CD20 directed antibodies (example: rituximab [Rituxan])

1. Classification: monoclonal antibody 2. MOA: binds to the CD 20 antigen on the cancer cell surface and recruits componenets of the immune system which then cause cell lysis 3. Indication: B-cell non-hodgkins lymphoma; CLL 4. Adverse effects: a. infusion reaction → hypotension; bronchospasm; angioedema b. tumor lysis syndrome → acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia (tx with fluids; dialysis; close monitoring c. mucocutaneous reactions → very serious skin reactions (should not receive this med again if this occurs) d. hepatitis B reactivation e. progressive multifocal leukoencephalopathy (PML) 5. Administration: IV infusion

Children

1. Combination therapy is stressed to limit SE and mutation of cells 2. Check dosage 3. Interventions to deal with potential need for isolation 4. Close monitoring of hydration and nutritional status

Monoclonal Antibody: trastuzumab (Herceptin) (the only example used in BC)

1. MOA: binds to the HER-2 protein (which is overexpressed in 25-20% of all primary breast cancers) inhibiting the growth of the tumor cells and contributing to the destruction of the BC cells that overexpress the HER-2 protein 2. Indication: HER-2 (+) metastatic BC; adjuvant therapy for HER-2 (+) BC; HER-2 (+) metastatic gastric cancer 3. Adverse effects: cardiotoxicity; flu-like symptoms; hypersensitivity reactions; infusion reactions; pulmonary events 4. stop the infusion if a reaction is assessed; assess for history of pulmonary disorders 5. Administration: IV infusion

Antiestrogens: example: tamoxifen (Nolvadex) (gold-standard for hormonal treatment of breast cancer)

1. MOA: blocks estrogen receptors on breast cancer cells to prevent receptor activation by estradiol to prevent tumor cell growth and multiplication. Target cells must be estrogen receptor (+) for this treatment to work. 2. Indications in Breast cancer a. as adjuvant therapy to suppress growth of left-over cancer cells after surgery b. treatment of metastatic disease c. for prevention of BC by decreasing risk in high-risk women

Gonadotropin-releasing hormone antagonists (example: degarelix [Firmagon])

1. MOA: blocks gonadotropin releasing hormone receptors in the anterior pituitary which decreases the release of luteinizing hormone and follicle stimulating hormone. This deprives the testes of the stimulation necessary for testosterone production. 2. Indication: palliative therapy of advanced prostate cancer 3. Adverse effects : (as per above) Does not cause an initial tumor flare like leuprolide d/t direct blockade of the receptors 4. Administration: SubCu

. CYP-17 inhibitors (example: abiraterone [Zytiga])

1. MOA: inhibits the production of androgens by the adrenal gland and the prostate itself 2. Indication: used to suppress androgen production in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel 3. Adverse effects: hypokalemia; hepatotoxicity (30% of patients); edema; joint swelling; muscle discomfort; hot flushes; diarrhea; UTI; cough; HTN 4. Administration: PO capsules on an empty stomach d/t increased risk of toxicity when taken with food which enhances absorption

Androgen-receptor blockers (example: flutamide [Eulexin])

1. MOA: inhibits the uptake of androgen as well as its binding to receptors 2. Indication: only for advanced PC and only in combo with surgical or chemical castration 3. Adverse effects: (as per above) occasional liver failure (high rate of first-pass metabolism) so liver function tests should be obtained at baseline and periodically through treatment 4. Administration: PO 5. Other examples: bicalutimide (Casodex); nilutamide (Nilandron; Anandron)

Angiogenesis inhibitors (example: bevacizumab [Avastin])

1. MOA: suppress formation of new blood vessel by binding with vascular endothelial growth factor, and therefore starve the tumor 2. Indication: metastatic colon/rectal cancer; non-squamous non-small cell lung cancer; metastatic renal cell carcinoma; glioblastoma

Gonadotropin-releasing hormone agonists (example: leuprolide [Lupron])

1. MOA: suppresses production of androgens by the testes only (not the adrenals or the PC cells) by mimicking the action of gonadotropin releasing hormone. It causes the pituitary to initially increase (causing an initial tumor flare-up) but then eventually decrease (due to desensitization from continuous exposure to leuprolide) to almost nothing, testosterone production by the testes. Produces "chemical castration" 2. Indication: advanced PC; palliation 3. Adverse effects: (as per above) 4. Administration: IM; SubCu

Cancer cells can develop resistance to drugs

1. cancer cell production of P-glycoprotein (pumps medication out of cells) is a major mechanism of drug resistance in cancer cells 2. induction od P-glycoprotein in cancer cells can happen during a single anti-cancer drug exposure and increases with each subsequent exposure 3. as therapy proceeds, the number of resistant cells will increase, which doesn't favor cure, as most patients require extended therapy

Platinum Compounds (cell-cycle non-specific)

1. cisplatin; carboplatin; oxaliplatin 2. MOA: similar to above 3. Specific example: cisplatin (Platinol-AQ) a. SE: can cause severe N/V that lasts for days; peripheral sensory neuropathy b. administration: IV infusion c. dose-limiting toxicity: kidney damage (limited with extensive hydration)

Cytotoxic Anti-Cancer Drugs

1. constitute the largest groups of anti-cancer agents 2. act directly on the cancer cells to cause their death 3. unfortunately, healthy cells are subject to their action as well

Pregnancy/nursing mothers

1. contraindicated 2. Barrier contraception for women of childbearing age receiving these drugs

4 major classes of anti-cancer drugs

1. cytotoxic agents (drugs that kill cells directly) (the term for classic "chemotherapy") 2. hormones and hormone antagonists 3. biologic response modifiers (immune modulators) 4. targeted drugs (drugs that bind with specific molecules that promote cancer growth)

Dosage, Handling, and Administration of Cytotoxic anti-cancer drugs

1. dosages MUST be individualized 2. timing of administration will vary with the particular protocol being followed 3. these drugs are mutagenic, teratogenic, and carcinogenic so must be handled very carefully 4. for these reasons, safe handling procedures must be followed 5. IV administration of vesicants must always be into a vein with good flow → central vein is best. These drugs qualify as vesicants: carmustine;dacarbazine; dactinomycin; daunorubicin; doxorubicinmeclorethamine; mitomycin; plicamycin; streptozocin; vinblastine; vincristine

Absence of true early detection (except for cervical cancer)

1. metastases may have formed 2. the tumor may be less responsive to drugs as it ages 3. long-standing malignancies often debilitate patients making them less likely to tolerate therapy well

Mechanisms of Cytotoxic Action

1. most agents disrupt processes related to the synthesis of DNA or its precursors 2. some agents block mitosis 3. one agent disrupts synthesis of proteins 4. all cytotoxic drugs except one (asparaginase) disrupt processes carried out exclusively by cells that are undergoing replication 5.as a result, these drugs are most toxic to cells that have a high growth fraction

Alkylating Agents (cell-cycle non-specific

1. nitrogen mustards; nitrosureas; others (busulfan; temozolomide) 2. MOA: injure cells primarily by forming covalent bonds with DNA thereby preventing DNA replication. Because alkylation reactions can take place at any time during the cell cycle, they are considered to be cell-cycle nonspecific.

Nausea and vomiting

1. occurs due to stimulation of the chemoreceptor trigger zone and can last for days 2. very severe and often debilitating 3. Premedication before chemo starts is helpful and often continue for 24-48 hrs after chemo finished

Limited drug access to tumor cells

1. poor blood supply to tumors (ex: large ones) ↓s ability to get drugs to the tumor. 2. Location of the tumor can also be a problem (ex: CNS tumors are difficult to treat since many drugs can't cross the blood-brain barrier)

Intermittent administration of chemotherapy

1. purpose = to allow normal cells to repopulate between rounds of treatment.... 2. but, if the cancer cells repopulate as fast as (or faster than) normal cells, no reduction in tumor will have been achieved with each round of treatment → treatment will fail

Older Adults

1.More susceptible to CNS and GI effects 2. Close monitoring of hydration and nutritional status 3. Close monitoring of renal and hepatic studies 4. Special consideration to immune status as the elderly are more likely to develop infections and less well-equipped to deal with them

Androgen Deprivation Therapy

A. General concepts 1. the deprivation of PC cells of the androgens they need for growth 2. benefits are typically limited to 18-24 months and then the cancer begins to progress again 3. General SE: hot flushes; ↓ libido; erectile dysfunction; gynecomastia; ↓ muscle and bone mass; ↑ risk for fractures

Glucocorticoids (example: glucocorticoids → prednisone [Deltasone]; dexamethasone [Decadron])

A. MOA: in cancer use, glucocorticoids are directly toxic to lymphoid tissue when used in high doses resulting in suppression of mitosis, dissolution of lymphocytes, regression of lymphatic tissue, and cell death B. Indication: ALL; CLL; Hodgkin's lymphoma; non- Hodgkin's lymphoma; multiple myeloma; also used to manage complications of cancer chemotherapy-induced N/V, reduction of cerebral edema (in patients with brain tumors), reduction of pain C. Adverse effects: more likely to occur with prolonged use 1. osteoporosis 2. adrenal insufficiency 3. increased susceptibility to infection 4. GI ulcerations 5. fluid/electrolyte imbalances 6. myopathy 7. diabetes mellitus

Targeted Anti-Cancer Drugs I. General Principles

A. are designed to bind with specific molecules (targets) on the cancer cells in order to suppress tumor growth B. the thought behind this is, that by looking for specific targets that are unique to cancer cells, cancer cells will be destroyed while normal cells will be spared C. General MOAs: 1.antibodies that target antigens on tumor cells 2. inhibit intracellular enzymes in the cancer cells 3. mark cancer cells for attack by the immune system 4. block cell-surface receptors 5. deliver toxic drugs or radioactivity 6. inhibit angiogenesis depriving tumors of blood supply

Immunostimulants I. General Principles

A. enhance the body's immune attack on cancer cells B. three agents are popularly used in cancer treatment

Principal Treatment Modalities for Prostate Cancer

A. localized cancer 1. Surgery 2. Radiation B. metastatic cancer 1. drug therapy → androgen deprivation therapy is most widely used 2. castration

Principal Treatment Modalities for Breast Cancer

A. surgery (primary therapy) B. radiation (primary therapy) C. cytotoxic drugs (adjuvant therapy) D. hormonal drugs (adjuvant therapy)

Antiestrogens: example: tamoxifen (Nolvadex) (gold-standard for hormonal treatment of breast cancer)

Adverse effects: a. hot flushes b. fluid retention c. vaginal discharge d. N/V e. menstrual irregularity f. thromboembolism (small risk) g. endometrial cancer (causes proliferation of endometrial tissue)(benefit outweighs risk however for treating BC)

S phase

DNA is synthesized/duplicated

Antiestrogens: example: tamoxifen (Nolvadex) (gold-standard for hormonal treatment of breast cancer)

Interaction with CYP2D6 inhibitors a. CYP2D6 is a liver enzyme that converts tamoxifen into its active form b. agents that inhibit this enzyme will interfere with the effectiveness of tamoxifen c. these agents (selective serotonin-reuptake inhibitors) (which are used to treat hot flushes) should be avoided by women who are taking tamoxifen for treatment of BC: 1) fluoxetine (Prozac) 2) paroxetine (Paxil) 3) sertraline (Zoloft)

Aromatase Inhibitors: example: anastrazole (Arimidex)

MOA: deprives BC cells of estrogen by inhibiting the enzyme aromatase (the enzyme that converts androgens in the tissue of post-menopausal women to estrogen) thus drastically reducing the production of estrogen in these women. 2. Indication: first-line therapy for post-menopausal women with estrogen-receptor positive BC 3. Adverse effects: generally well-tolerated; musculoskeletal pain; weakness; HA; menopausal Symptoms

G1 phase

RNA and proteins are synthesized→ prepares to make DNA

Three major cancer treatment modalities

Surgery, Radiation, Drug therapy/Chemotherapy

BRAF V600 kinase inhibitor (example: vemurafenib [Zelboraf])

a. Indication: unresectable or metastatic melanoma that expresses the above kinase b. Adverse effects: cutaneous squamous cell carcinoma (24%); hepatotoxicity; severe hypersensitivity; severe skin reactions (Stevens-Johnson syndrome); ,serious ophthalmic reactions; dysrhythmia

procarbazine (Matulane) (cell-cycle non-specific)

a. MOA: a prodrug that undergoes metabolism in the liver → the metabolites suppress the synthesis of DNA, RNA, and protein b. SE: N/V; neurotoxicity; sterility (especially in males) b. Indication: lymph cancers; primary brain cancer (active metabolites are highly lipid soluble and facilitate crossing of the BBB) c. Administration: PO d. Dose-limiting toxicity: bone marrow suppression

Asparaginase (Elspar; Erwinase)

a. MOA: an enzyme that converts the amino acid asparagine, into aspartic acid. By doing this, it deprives cells of asparagine that is needed to synthesize proteins b. Adverse effects: coagulation deficiency; CNS depression; hypersensitivity (it is a foreign protein); does not depress bone marrow, cause alopecia, or enteral tract ulceration c. Sole Indication: acute lymphocytic leukemia reactions d. Administration: IM; IV e. Dose-limiting toxicity: individually determined since it doesn't cause bone marrow suppression

Interferon Alfa-2b

a. MOA: binding of this drug results in induction of enzymes, suppression of cell proliferation, enhancement of the phagocytic activity of macrophages, and augmentation of lymphocyte activity b. Indication : melanoma; hairy cell leukemia; CML; AIDS- related Kaposi's sarcoma c. Adverse effects: flu-like syndrome; anorexia; weight loss; diarrhea; dizziness; cough d. Administration: SubCu; IM; IV

epidermal growth factor receptor (EGFR) TKI (example: cetuximab [Erbitux])(monoclonal antibody)

a. MOA: blocks EGFRs by working as a competitive antagonist, thus inhibiting cell growth and promoting apoptosis (programmed cell death). Works only on cancer cells that overexpress EGFR; doesn't work on those that don't have EGFR. b. Indication: head and neck cancer; colorectal cancer

Aldesleukin/Interleukin-2 (Proleukin)

a. MOA: nearly identical to human IL-2; stimulates immune function to enhance anti-tumor activity b. Indication : metastatic renal cell carcinoma; metastatic melanoma c. Adverse effects: significant toxicity → fever, chills; N/V; hypotension; anemia; diarrhea; altered mental status; pulmonary congestion d. Administration: IV infusion

BCR-ABL tyrosine kinase inhibitors (example: imatinib [Gleevec])

a. MOA: prevents activation of regulatory proteins and suppresses proliferation of chronic myelogenous leukemia cells and promote apoptosis b. Indication: blood cancers c. Adverse effects: N/V/D; rash; HA; fatigue; fever; musculoskeletal complaints; fluid retention that can lead to pleural effusion or pulmonary edema; neutropenia; thrombocytopenia (see previous nursing implications for these) d. Administration: PO tablets to be taken with a meal and a large glass of water

Anti-tumor Antibiotics (cell-cycle non-specific)

a. anthracyclines: doxorubicin; daunorubicin; epirubicin; idarubicin; mitoxantrone; b. Non-anthracyclines: dactinomycin; bleomycin; mitomycin

preferred regimen for N/V

a. aprepitant (Emend) (neurokinin-1 receptor (NK-1) antagonists) (PO;IV) b. dexamethasone (Decadron) (1 dose IV before chemo followed by PO dosing x 3 days after chemo) c. serotonin antagonist (5-HT3-receptor antagonist) (ex: ondansetron (Zofran); granisetron (Granisol; Kytril); palonosetron (Aloxi) ; dolasetron (Anzemet) (beware of cardiac arrhythmia)

Ideally, the drugs used in combination therapy should have

a. different mechanisms of action b. minimally overlapping toxicities c. good efficacy when used alone

Cell-cycle specific drugs

a. effective only during a specific phase of the cell cycle (e.g., S phase, M phase). b. therefore, they are active only against cells that are participating in the cell cycle c. resting cells in the G0 phase are not affected by these agents d. to be effective, phase-specific drugs must be present as neoplastic cells cycle through the phase in which the drug acts. e. this means that phase-specific drugs must be in the blood continuously over a long time.

Nursing implications for Stomatitis

a. good oral care (soft tooth brush or wipe teeth with a soft cloth) b. rinse mouth several x daily (1 tsp baking soda + 1 tsp salt + 1 quart H2O) c. plenty of non-carbonated, non-acidic fluids d. soft, bland, cold, non-acidic foods e. remove dentures for at least 8 hrs/day f. local analgesia (ex: viscous lidocaine and an antihistamine mixed, as a mouth wash) g. inspect oral cavity and treat any infection → ex: candidiasis

Multidrug chemotherapy is generally much more effective than single-drug therapy

a. suppress drug resistance b. increase cell kill c. reduce injury to normal cells (at any given level of anticancer effect)

Mitotic Inhibitors (cell-cycle specific, usually M-phase)

a. vinca alkaloids: [vincristine (Oncovin); vinblastine (Velban); vinorelbine (Navelbine)] b. taxanes: "antimicrotubules" [docetaxel (Taxotere); paclitaxel (Taxol)] MOA: are plant alkaloids and other compounds derived from natural products that block cell division at the M-phase

Progestins: medroxyprogesterone acetate (Depo-Provera)

advanced endometrial and renal cancer; megestrol acetate (Megace) → advanced endometrial and breast cancer. They induce enzymes that metabolize estrogen thus decreasing the growth of these types of cancers

Lenalidomide

an analog of thalidomide used to treat multiple myeloma and to increase red blood cell counts in patients with transfusion-dependent anemia. Associated with serious toxicities including thrombocytopenia and neutropenia. Also teratogenic.