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Drugs for NeoplasiaChapter 37

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Cancer in the U.S.

2007 Prevalence: 11.7 Million Males: 5.36 M; Females: 6.37 M2008: New Cancer Cases

745,000 Males 692,000 Females Estimated Deaths 294,000 Males 272,000 FemalesAmerican Cancer Society 2011

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Cancer in the U.S.

• Leukemia: most common childhood cancer, makes up 25% of all cancers for <20 age group

• Lung Cancer has highest mortality rate-28% of all cancer deaths.

• Pearson Education, Inc., 2011 (Am. Cancer Society 2008)

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Description & Pathogenesis

• Neoplasm = new tissue mass or Tumor• Carcinoma or Cancer = abnormal,

uncontrolled cell division or tissue growth. • Oncogenes: genes that cause cancer(?)

(Members of one family develop the same type of cancer.)

• Damaged tumor suppressor genes?• Pearson Education, Inc. 2008, 2011

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PathogenesisViruses are associated with 15% of all cancers:

Herpes Simplex Virus Epstein-BarrCytomegalovirus

Human Papillomavirus (HPV)

HIV & Transplant Medications :weaken or suppress the immune system

• Pearson Education, Inc. 2008

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Environmental Risk Factors

Alcohol → Liver Cancer

Asbestos → Lung Cancer

Benzene → Leukemia

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More Risk Factors

• Tobacco → Lung, Head, Neck Cancer(1/3rd of all Cancer in U.S.)

• X Rays/Radiation → Leukemia

• Sun → Skin Cancer• Pearson Education, Inc. 2008, 2011

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Cancer Treatment

• Surgery• Radiation therapy• Drug therapy (chemotherapy) – To cure– To control– For palliation– For prophylaxis

• Pearson Education, Inc. 2008, 2011

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Cancer Treatment

Surgery– Remove localized, solid Tumor– Reduce numbers of cancer cells– When compromising blood flow, breathing, or

causing pain (Palliation).

Radiation– Localized Tumor, follow up after Surgery, or

palliation for inoperable Cancers

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Chemotherapy

• Transported through blood– Has potential to reach each cancer cell

• Some drugs can cross blood-brain barrier• Some drugs instilled directly into body cavities

(ex: bladder)• Often combined with or done after surgery and

radiation to increase chance of cure (adjuvant therapy).

• Pearson Education, Inc. 2008

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Chemotherapy

• Cancer Cells mutate and also develop resistance, making for a difficult cure

• More toxic or effective upon tumors/cells that have a high Growth Fraction (greater ratio of replicating vs. resting cells).

• Multi-drug Protocols: smaller dose of each drug, may reduce adverse effects

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Case Study

• Mr. C. is a 57 y.o. white male with a history of duodenal ulcer, Right Total Hip Replacement, pneumonia, HTN, 20 pack/yrs smoker (10 cigarettes/day X 40 years), and a recent onset of weakness, loss of appetite, constipation and fatigue. He was diagnosed with a partial bowl obstruction due to adenocarcinoma. Mr. C. just completed a course of Radiation and has now been admitted to the Cancer Care Unit status post (s/p) Sigmoid Colectomy.

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Admission Orders

• IV Dextrose 5% in Water (D5W) at 125 cc/hr• IV Fluorouracil (5-FU) 12mg/kg/day X 4 days• Cyclophosphamide (Cytoxin) 5 mg PO daily X

5, then 3 mg PO weekly• Morphine PCA 2 mg IV/hr basal rate, 1 mg q 6

min PRN, max 12 mg/hr lock out, for pain

• Pearson Education, Inc. 2008, 2011.• Nursing Drug Handbook 2008

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Admission Orders

• Ondansetron (Zofran) 4 mg IV 30 minutes before meals and Q2h PRN N/V

• Sips of water then Clear Liquid diet as tolerated after passing flatus

• Up with assistance• Intake and Output

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Antineoplastic Drugs

• Several different categories of Chemotherapeutic Drugs are derived from plants, bacteria and/or laboratory synthesis. The drugs have diverse actions against Cancer cells, disrupting DNA or RNA production, or having toxic action against metabolic pathways. The result is a slowing or stopping of growth, and/or killing of the cancer cell. Antineoplastic Drugs are more effective against rapidly replicating cells.

• Pearson Education, Inc. 2008, 2011

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AntimetabolitesStructurally similar to folic acid, purines and pyrimidines, which are essential for DNA & RNA synthesis, Antimetabolite Drugs are analogs to Vitamin B9 and nucleic acids. These drugs do not function in the same way, rather they disrupt or slow cancer cell growth or cause their death. Antimetabolites are usually prescribed for leukemia's and solid tumors.wikipedia.org Pearson Education, Inc. 2008, 2011

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Fluorouracil (5-FU)

• Antimetabolite Category (Pyrimadine Analog)• Action: disrupts and slows cancer cell growth in

the ‘S’ Phase (DNA synthesis) of the Cell Cycle, causing cell death.

• Adverse Effects– Common: N/V, stomatitis, anorexia, rash, H/A, alopecia– Serious: Bone Marrow suppression, severe N/V/D,

hepato/pulmonary/neurotoxicity, mucositis, hypersensitivity reactions

• Pearson Education, Inc. 2008, 2011

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Cyclophosphamide (Cytoxan)

• Alkylating Agent (nitrogen mustard)• Action: Cytoxan changes or disrupts the shape

of the DNA Double Helix which slows or interrupts normal cellular division and causes cellular death.

• Pearson Education, Inc. 2008, 2011

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Cytoxan

• Adverse Effects: – Common: N/V, anorexia, stomatitis, rash, H/A,

alopecia, fluid retention– Serious: Bone Marrow suppression, severe N/V/D,

Stevens-Johnson syndrome, hemorrhagic cystitis, pulmonary toxicity, hypersensitivity reactions , nephrotoxicity, sterility. (5% develop acute nonlymphocytic leukemia 4 or more years later.)

• Pearson Education, Inc. 2008, 2011

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Cytoxan

Contraindications:– Hypersensitivity reactions– Active infections– Severely suppressed bone marrowDrug-Drug Interactions: Cytoxan used along with

Immunosuppressant agents increases risk for infection and neoplasm, bone marrow toxicity if used with allopurinol.

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Nursing Process: Assessment

• Review Health Hx. : physical exam (current infection?), labs, current medications, neurological (mood, sensory impairment).

• Caution: immunosuppressive drugs cause risk of exacerbation of Herpes Zoster in patients with Hx of herpes/chicken pox.

• Pearson Education, Inc. 2008

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Nursing Diagnosis

Which potential or actual Nursing Diagnosis do you think would apply to Mr. C.?

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Potential/Actual Nursing Diagnosis• Infection, Risk for, related to

compromised immune system• Pain, Acute, related to Surgical Incision• Nutrition, Imbalance, Less than body

requirements 2nd to n/v/d, anorexia from drug side effects, limited oral intake

Pearson Education, Inc. 2008

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Potential/Actual Nursing Diagnosis

• Skin Integrity, Impaired, related to extravasation• Body Image, Disturbed, due to physical

changes as a result of drug side effects• Activity Intolerance/Fatigue/Risk for

Injury/Falls, related to decreased RBC production due to drug side effect and/or poor nutritional intake, and/or muscle wasting.

• Pearson Education, Inc. 2008, 2011

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Planning: Client Goals & Expected Outcomes

• The Client will:– Experience a reduction in tumor mass or

progression of abnormal cell growth–Maintain WBC’s >4,000, Platelet’s >50,000, CBC

WNL, Absolute Neutrophil Count (ANC) > 500/mm3

– Demonstrate understanding of drug action by describing use, side effects & precautions

• Pearson Education, Inc. 2008, 2011

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Planning: Client Goals & Expected Outcomes

• Good pain management, tolerate gradual progression of increasing activity and maintain ADL’s, quality rest/sleep

• Experience minimal or no adverse drug effects» Pearson Education, Inc. 2008, 2011

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ImplementationInterventions/Rationales Patient & Family Education

Monitor for Hypersensitivity / Adverse Reactions

-Observe for/Client immediately reports chest/throat tightness, problem swallowing, facial swelling, abd pain, H/A, dizziness

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Implementation/Education

Protect from Infection: Monitor Labs and VSS (watch for blood dyscrasias and compromised immune system)• Client reports increasing fatigue or cough, sore throat,

fever > 100.4, chills/sweats, freq./painful urination, rash/blisters• Avoid crowds/people with infections/cut flowers or change H2O daily using 1 tsp bleach• Frequent hand washing, oral hygiene, ongoing

assessment of opportunistic infections• Pearson Education, Inc. 2008• Black, J., & Hawks, J., 2009

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Implementation

Protect from Infection Cont’ed:• Adequate nutrition/fluid intake, avoid raw

fruits/vegetables (family prep/clean up, must cook thoroughly) or • Take periods of rest between activities, avoid

demanding tasks/avoid activities requiring mental alertness till drug effects are known• Institute Protective Isolation if Neutrophil

Count <500/ml

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Implementation

• Assess for Pain– Provide adequate pain relief from surgery or drug

adverse effects– Instruct patient/family in pain management (pain

scale, when to medicate, reassessment, call for assistance, etc.).

– IV Monitoring: Chemotherapy - Vesicant - risk of extravasation, causing severe tissue injury, nerve damage, infection and even loss of limb.

• Pearson Education, Inc. 2010

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Implementation

• Monitor VSS & Cardiopulmonary status including EKG changes– Client reports any respiratory distress or chest,

arm, neck or back pain, edema or activity intolerance

– Keeps all scheduled medical/lab appointments. Adverse effects may not appear until 6 months after treatment (tx).

• Pearson Education, Inc. 2008

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Implementation

• Monitor Renal status (I&O, lab values, daily weights). – Client reports changes in thirst, character and/or quantity

of urine, low back/flank pain, trouble voiding, weight gain– Observe for blood in urine months after treatments– Drink 2-3 liters of water, in small portions, 1 day before

tx, and daily for 72 hrs after tx (if no fluid restrictions & pt. can tolerate)

– Encourage pt. to urinate Q1-2 hrs while awake to help avoid hemorrhagic cystitis

• Pearson Education, Inc. 2008• Nursing Drug Handbook 2008

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What do you see?

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Implementation

• Monitor Gastrointestinal (GI) status & Nutrition, administer antiemetic 30 minutes before meals– Client reports anorexia, n/v/d, mouth discomfort

(mucositis). – Eat small frequent meals, avoid hot, spicy, difficult to

chew and strong odor foods– Drink plenty of cool liquids– Examine mouth for irritations/sores, good hygiene,

use soft toothbrush, no toothpicks• Pearson Education, Inc. 2008, 2011

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Implementation

Monitor GI and Genitourinary (GU) status– Monitor for constipation and report change in

bowl habits, increase fiber, fluids and activity as ordered &/or tolerated

– Report changes in menstruation, sexual function, vaginal discharge

Pearson Education, Inc. 2008

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Implementation

• Collect Fecal Occult Blood Specimens (FOB)(Drugs may cause GI bleeding)

Client to report epigastric pain, coffee-ground emesis, tarry stools or frank bleeding, bruising. Avoid ASA (aspirin), NSAIDS (non-steroidal anti-inflammatory drugs).

Each antineoplastic drug has a documented Nadir, the lowest point at which RBC’s, WBC’s and Platelet counts are depressed. Monitor absolute neutrophil counts. Administer growth factors as ordered (granulocyte colony-stimulating factor, etc.) which help shorten periods of neutropenia.Pearson Education, Inc. 2008, 2011

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Implementation

• Monitor Neurological & Sensory Status– Client to report change in skin color, vision (pain,

halo), hearing (ringing, buzz), gait, mood, sensations (numbness or tingling) or any dizziness, vertigo. (Cytoxin can cause ototoxicity.) Encourage periodic ear and eye exams. Assess transportation needs and ability to drive, make social service referral prn.

– Limit exposure to sun, use sunscreen, sun glasses, long sleeve shirts

• Pearson Education, Inc. 2008, 2011.

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Implementation

• Monitor hair and skin status– Report any loss of or sloughing of skin or hair,

rash, purple-red blisters, pruritis, acne or boils– Wear cold gel cap during chemotherapy to help

minimize hair lossPearson Education, Inc. 2008

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Implementation

• Monitor Liver Function Tests (LFT’s)– Report jaundice, abd pain, tenderness, bloating,

change in stool color or consistency– Keep all lab appointments.Caution in treating pt.’s with Diabetes Mellitus:

monitor daily blood sugar levels, notify provider of hypoglycemia (<80 mg/dl)

Pearson Education, Inc. 2008

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Implementation

• Antineoplastic Administration: Nursing Policy and Procedures

– Safety– Chemotherapy Certification– IV pump– Equipment & drug disposal– Spill management

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Evaluation of Outcomes

• Client exhibits reduction of progression of Tumor mass

• WBC’s >4,000, Platelet’s >50,000, • CBC & ANC WNL• Client demonstrates an understanding of drug

actions by accurately describing side effects and precautions

• Pearson Education, Inc. 2008

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Mr. C.

• It is now 2 days post op and Mr. C. has had two rounds of 5FU and 4 rounds of Cytoxin. His lymph node pathology report states 12 of 17 nodes were positive for cancer cells. His pain is well controlled with the Morphine, however he has had significant N/V and has not tolerated a clear liquid diet. The MD has ordered Phenergan Suppositories 25 mg PR Q6H ATC which has provided good relief, and has changed the IV to D5 & 1/2 NS with 20meq/KCl at 125cc/hr.

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Mr. C.

• Mr. C.’s lab results show a drop in his WBC’s to 2.2 (pre-op 4.5), Platelets 73,000 (pre-op 138,000) & ANC of 400mm3. What nursing behaviors would be appropriate?

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Mr. C.

• The nurse assesses for infection and bleeding. After conferring with the MD, the nurse places Mr. C. on protective isolation. She educates Mr. C. that he is at greater risk of infection due to his low white blood cell count and instructs him to avoid exposure to others who are ill or infectious. She also advised Mr. C. that he may bleed or bruise more easily and to be careful to avoid any injury.

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Other Antineoplastic Agents

• Antitumor Antibiotics: isolated from microorganisms or bacteria, are more toxic than standard antibiotics.

• Action: bind to DNA, disrupting replication and or causing cell death (similar to Alkylating Agents) with similar side effects.

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Antitumor Antibiotic: Doxorubicin

• Action: a prototype drug, Doxorubicin (Adriamycin) attaches to DNA and distorts the helix, preventing normal DNA and RNA synthesis. It is a broad spectrum antibiotic, given IV only. Doxorubicin liposomal (Doxil), has a unique method of delivery via lipid vesicles, or liposomes, which open in close proximity of cancer cells, sparing normal tissue. Very effective against solid tumors.

• Pearson Education, Inc 2008, 2011.

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Doxorubicin60-75mg/meter squared (m2) IV q 3 weeks

• Adverse Effects: – Common: acute n/v, alopecia, anorexia, stomatitis,

rash, H/A– Serious: Cardiotoxicity: dysrhythmias and

irreversible heart failure. Bone marrow suppression, extravasation can cause severe pain and extensive tissue damage. Severe n/v/d, mucositis, pulmonary toxicity, hypersensitivity reactions (including anaphylaxis). Acute myelogenous leukemia may occur 1-3 years later.

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Natural Products Category: Plant Extracts & Alkaloids

• Prototype Drug: Vincristine (Oncovin)• Actions and Uses:

Vincristine, a Vinca Alkaloid from the periwinkle plant, is a cell-cycle-specific agent that prevents cells from completing mitosis by interrupting the M-phase of replication, has a broad spectrum of activity and causes minimal immuno-suppression. Treats pediatric leukemia's, lymphomas, and solid tumors.

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Vincristine (Oncovin)1.4mg/m2 IV weekly

• Adverse Effects:– Common: N/V, alopecia, anorexia, stomatitis, rash,

asthenia – Serious: Bone marrow suppression, Severe n/v/d,

mucositis; cardio, pulmonary, neuro and nephrotoxicity; hypersensitivity reactions (including anaphylaxis).

• Pearson Education, Inc. 2008• Nurse’s Drug Guide 2009

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Hormones & Hormone Antagonists

• Actions and Uses: Very large doses of glucocorticoids, progestins, estrogens or androgens that block essential substances for the growth of hormone-dependant tumors of the brest or prostate. As a group, they are the least toxic of the antineoplastic drugs.

• Pearson Education, Inc 2008, 2011

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Tamoxifen (Nolvadex)

• Actions and Uses: Tamoxifen is the prototype antineoplastic drug in the Hormone Antagonist (antiestrogen) Class. It is the drug of choice for treatment of metastatic brest cancers which have cells that require estrogen for growth (estrogen receptor positive). Also, Tamoxifen is given prophylactcally to high-risk clients to prevent the disease.

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Tamoxifen (Nolvadex)10-20 mg PO daily/BID

• Adverse Effects:–Common: hot flashes, insomnia, brest

enlargement & pain, H/A, N/D, asthenia, vaginal discharge, fluid retention–Serious: hypersensitivity reactions (including

anaphylaxis), thromboembolic disease, sexual dysfunction, HTN, increased risk for endometrial CA

• Pearson Education, Inc 2008, 2011

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Biologic Response Modifiers & Immune Therapies

• Action and Uses: This group of drugs modify and or stimulate the bodies own immune system to fight the cancer cells. This class includes Interferons, Interleukin-2, and Monoclonal antibodies.

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interferon alfa-2 (Intron-A)

• Actions and Uses: This prototype drug is naturally produced by T cells in response to viral and biological stimuli. Interferons possess a generalized action, suppressing cell division, enhancing phagocytic activity and promoting cytotoxic action of T lymphocytes. Treats Hairy Cell Leukemia, Kaposi’s Sarcoma (KS) and chronic Hepatitis B or C.

• Pearson Education, Inc. 2011

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interferon alfa-2 (Intron A)(leukemia 2-3 million, Kaposi Sarcoma 36

million units daily SubQ/IM)

• Adverse Effects:–Common: stomatitis anorexia, N/V, ,

alopecia, stomatitis, rash, asthenia, –Serious: Bone marrow suppression,

severe n/v/d, pulmonary toxicity, hypersensitivity reactions (including anaphylaxis)

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Monoclonal Antibodies (MABs)

• MAB’s are engineered or synthesized to attack one specific tumor antigen (protein). Upon binding to the cancer cell, the cancer cell is identified by the host as foreign. Rituzamab and Alemtozumab kill cancer cells via phagocytosis, compliment fixation, and apoptosis. Cetuximab and Trastuzumab stop tumor cell growth by inhibiting growth factor receptors.

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Mr. C.

• 5th day post op Mr. C. is managing clear liquids in small amounts and remains afebrile. His WBC’s remain low at 3.9 and his Platelets are 59,000. His incisions are healing, and he has had a small BM. Upon discharge, he will continue to receive treatment with 5FU and Cytoxan at the Out Patient Oncology Unit (OOU).

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Mr. C.

• Mr. & Mrs. C. understand that they are to watch for fever, increased fatigue and avoid people with infections. They will call to arrange appointments with the OOU and also keep their appointments with the Surgeon and Oncologist. The Visiting Nurse Association (VNA) will follow up with twice weekly home visits and provide referrals to Home Health Agencies and Care Giver Support Groups as needed.

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Mr. C.

• A Port-a-Cath has been placed in his right upper chest. The nurse asks him if he is feeling depressed. She provides support and active listening as he shares his concerns. The nurse contacts his brother at his request. As the nurse leaves the room, Mr. C. smiles and says, “I’ll be fine.”

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Discussion/Reflections

• What QSEN Competencies could be applied to this scenario?

• What stressors, lines of defense and resistance and reactions could be involved when discussing the Neuman Systems Model?

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Cancer Vaccines• April 2010, FDA approved first cancer treatment vaccine, sipuleucel-T

(Provenge®). It stimulates an immune response for prostatic acid phosphatase (PAP), an antigen associated with prostate cancer. Men who had a specific type of metastatic prostate cancer received Sipuleucel-T demonstrated an added survival of by about 4 months (19).

• The U.S. Food Drug Administration (FDA) has approved two new vaccines, Gardasil® and Cervarix®, and that protect against infection by two types of HPV that cause approximately 70 percent of all cases of cervical cancer (vaginal, vulvar) worldwide, as well as anal, penile, and oropharyngeal cancers (10).

• In 1981, The FDA approved the first cancer preventive vaccine that protects against HBV infection. Chronic HBV infection can lead to liver cancer. Today, most children in the United States are vaccinated against HBV shortly after birth (12).

• http://www.cancer.gov

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ReferencesPharmacology for Nurses, A Pathophysiological Approach, 2nd Ed., 2008, 3rd

Edition 2011 Pearson Education, Inc.American Cancer Society 2011Nursing Drug Handbook 2008, Lippincott, Williams & WilkinsNurse’s Drug Guide 2009, Prentice Hallhttp://www.merck.com/mmhe/sec09/ch131/ch131i.htmlen.wikipedia.org/wiki/Purinehttp://www.cancer.gov Retrieved 10/18/10Medical-Surgical Nursing: Clinical Management for Positive Outcomes, 8th Ed.

2009, Black, J., Hawks, J. Saunders/Elsevier Inc.