Toxicities: Long term

Question 1

What is the mechanism for long-term lung toxicity?

Answer 1

• Progressive and often irreversible inflammation reaction, resulting in drug-induced pneumonitis
• Damages endothelial lung cells

Question 2

What drugs are highly implicated in LT lung toxicity?

Answer 2

• Bleomycin
• Carmustine
• Lomustine may cause pulm fibrosis
• Bulsulfan

Question 3

What are the S&S and timing/onset for LT lung toxicity?

Answer 3

• Long-term use, often greater than 3 years (but can be as quick as 6 weeks)
• Cough, SOB, dyspnea/tachypnea, rales
• Low grade fever
• Hypoxemia
• Pulmonary fibrosis
• Capillary leak syndrome (with cytarabine)
• Interstitial fibrosis (with methotrexiate)
• Older age, smoking hx, renal dysfunction and thoracic radiation risk factors

Question 4

What are the treatment and prevention strategies for LT lung toxicity?

Answer 4

• Short term steroid therapy
• Dry cough suppressant
• Symptom control (eg. O2 prn)
• Monitor resp status
• d/c or alter treatment regime
• Routine vaccinations (eg. flu vac)
• Smoking cessation
• exclude infection
• pulm function tests
• education re: breathing techniques and energy/activity

Question 5

What is the mechanism of action for LT hepatotoxicity?

Answer 5

• Transient increases in hepatic enzymes = hepatomegaly & jaundice
• Damage to parenchymal cells
• Rare, but if it occurs can have serious implications (esp since many chemo drugs excreted via liver)
• Risk factors: prior liver damage (eg. hepatitis), alcoholism, increased age, obesity, any tumor involvement, comorbidities (eg. DM)

Question 6

What drugs are implicated in LT hepatotoxicity?

Answer 6

• Carboplatin (endings with - platin)
• Cytrabine (endings with - abine)
• 5-FU
• Dacarbazine
• Methotrexate

Question 7

What are the S&S and timing/onset of hepatotoxicity?

Answer 7

• Jaundice (urine and stool color changes)
• Tenderness at site
• Elevated LFT’s
• General signs liver failure (eg. decreased clotting, fatigue, ascites)

Question 8

What is the prevention and management strategies for LT hepatotoxicity?

Answer 8

• Can occur after multiple treatments or 1-4 weeks after starting
• Monitor LFT’s, adjust tx or stop accordingly
• Supportive measures if progressed (eg. diuretics, decrease protein intake, lactulose, etc.)

Question 9

What are common reproductive system dysfunctions that occur and can be a long-term issue? Why?

Answer 9

• Erectile dysfunction in men
• Pain with intercourse (dyspareunia) with both men and women
• Decreased libido
• Affects QOL for the patient and their partner
• Changes in body image
• Appears that sexual dysfunction often related to surgery changing the structures, nerves, etc. and/or treatments that can induce reproductive changes (eg. hormonal changes from meds can cause vaginal atrophy in women, decreasing elasticity; radiation therapy; chemotherapy)

Question 10

Discuss infertility in relation to Ca and it’s treatment:

Answer 10

• Infertility = inability to conceive after one year of unprotected intercourse
• For adolescents and young adults the risk of infertility with Ca is 50-95%
• Multiple risk factors in this group (eg. diagnosis, age, type of maligancy and stage, and the treatments - surgery, radiation, hormone manipulation, and the length can lead to delays in pregnancy attempts)
• There is a lack of information about preserving fertility
• In women, fertility often d/t premature ovarian failure from antineoplastic treatments
• In men, infertility is a long-term effect of hypogonadism (azoospermia) d/t germ cells being more sensitive to rad and chemotherapy

Question 11

What drugs are implicated in altered fertility?

Answer 11

• Bulsulfan
• Chlorambucil
• Cyclophosphamide
• Anti-hormone agents

Question 12

What are signs of altered sexual function and fertility?

Answer 12

• Irregular menstruation / amenorrhea
• menopause symptoms - hot flashes
• Infertility - inability to conceive after trying for a year
• Erectile dysfunction
• Pain with intercourse (both male and female)
• Changes in libido

Question 13

What are preventative and management strategies for fertility?

Answer 13

• Ensure that provider-pt relationship is open and you demonstrate comfort in discussing
• Consider the $$ involved in treatments (pt’s may already be under a lot of $ stress)
• Education re: options for fertility - egg or sperm banking
• Contraceptive information to avoid pregnancy while on active therapy
• Emotional support
• Ensure pt and partner understands the potential for temporary or permanent infertility and sexual changes with treatment

Question 14

Describe ocular toxicities:

Answer 14

• Relatively uncommon but can occur
• Can occur in multiple structures, including outside (eyelids) and interior
• Neurotoxic side effects of chemo tend to be peripheral neuropathies but central neurotoxicities can occur

Question 15

What drugs are highly implicated in ocular toxicity?

Answer 15

• Most common ocular side effect is blepharitis, inflammation of the eyelids
• Can also cause excessive tearing, conjunctivitis, dry eyes, and in some cases can cause cataracts and glaucoma to develop secondary to Ca treatment
• Long-term radiation can cause ocular complications
• 25-50% of patients receiving 5-FU can experience ocular tox
• Cetuximab
• Methotrexate

Question 16

What are common symptoms of ototoxicity?

Answer 16

Damages to inner ear, causing tinnitus, pain, vertigo and hearing loss (unlikely reversible)

Question 17

What are drugs implicated in ototoxicity?

Answer 17

• platins (alkylating agents) such as cisplatin, oxaliplatin, carboplatin
• stine’s (alkaloids) such as vinblastine and vincristine
• MAb’s and TKI’s can cause vertigo
• Radiation therapy (esp for head & neck Ca)

Question 18

What causes otoxocity?

Answer 18

Unknown, but believed to be effects to the cochlea and vestibular cells of the inner ear

Question 19

How do you prevent and/or manage ototoxicity?

Answer 19

• Baseline audiogram
• Monitor for symptoms of tinnitus, hearing loss and vertigo
• Ensure safety precautions for vertigo, especially if severe

Question 20

What are secondary malignancies?

Answer 20

• Ca caused by treatment by chemo/radiation for the 1st, unrelated Ca, d/t affected normal cells from the treatment
• can occur months/years later
• certain groups of Ca and treatment regimes more likely (combo rad/chemo more likely compared c single therapies; groups like childhood leukemia, breast, testicular and ovarian Ca higher risk) and some drugs have higher incidence (cisplatin)

Question 21

What are nursing indications for secondary malignancies?

Answer 21

• Original treatment plan may take into consideration how to prevent secondary malignancies (eg. try to avoid high carcinogenic potential, avoiding radiation therapy, identify regimes that are higher risk)
• Emotional support
• Education for what to monitor for (eg. notify doctor immediately of any irregularities) and screening regimes (eg. starting mammography screening sooner)

Question 22

What is the mechanism of action for cardiac toxicity?

Answer 22

• Can be from chemo and targeted therapies, as well as chest radiation
• Chronic damage to myocardial cells
• Ca treatments can pose unique direct problems to the heart (myocardial toxicity, ischemia, HTN, arrhythmias) and indirect heart problems (eg. having to make unfavorable lifestyle changes)
• Cardiac toxicity can even be the cause of mortality over the cancer itself in some groups

Question 23

What are common CV adverse events r/t cardiac toxicity?

Answer 23

• Heart failure - the most serious consequence
• HTN (TKI’s often causative)
• Thrombosis and ischemia (combined therapies may increase risk)
• Rhythm disturbances (QT prolonged wave) leading to arrhythmia’s (some medications like anti-emetics and anti-depressants can contribute to this as well)
• Radiotherapy induced CV damage (CAD, myocardium damage)

Question 24

What drugs are highly implicated in cardiac toxicity?

Answer 24

• Doxorubicin and daunorubicin (doxo often causes changes in HR and rhythm during or after admin)
• Paclitaxel
• Trastuzumab
• 5-FU

Question 25

What are the S&S of cardiac toxicity?

Answer 25

- Most often asymptomatic until S&S of CHF present | - Changes in HR or rhythm

Question 26

What are preventative and management strategies for cardiac toxicity?

Answer 26

- Baseline studies (eg. ECG, echocardio imaging to determine LVEF, cardiac enzymes [trops]) and periodic monitoring - Monitor for S&S cardiac symptoms (eg. SOB, changes in activity tolerance) and educate pt re: changes to monitor for - Monitor accumulative life time dosage - Cardiac protective agents (eg. beta blockers, anti-hypertensives) - Anticoagulants generally not recommended to prevent clots at this time (d/t concern of bleeding complications)

Question 27

What toxicity is second only to myelosuppression as a dose-limiting factor of Ca treatment?

Answer 27

- Neurotoxicity - Treatments affect both central and peripheral systems - Important to recognize to prevent further injury and to distinguish from nervous system involvement d/t the disease

Question 28

What is the mechanism of injury for neurotoxicities?

Answer 28

- Damage to sensory nerve tissues (85-95%) - Heightened immune responses can damage nervous system cells - Nervous system cells contain stem cells that replenish some neuron populations and divide (albeit slowly) - Radiation therapy can cause damage directly or indirectly by causing vascular damage, endocrine disturbances and fibrosis of structures - Often delayed by weeks to years (slow rate of cell turnover)

Question 29

What are central nervous system toxicities that are seen?

Answer 29

- HA and acute altered mental status most common - Seizures - Encephalopathy - Cerebrovascular disease - increase risk strokes - Cerebellar dysfunction - Movement disorders - Radiation necrosis - Secondary nervous malignancies - Spinal cord syndrome

Question 30

What are peripheral nervous system toxicities?

Answer 30

- Plexopathy (brachial and lumbosacral) - weakness, sensory impairment, pain - Peripheral neuropathy - most common and can be dose-limiting - Myalgias - Acute inflammatory demyelinating polyneuropathy

Question 31

What are highly implicated drugs in nervous system toxicity?

Answer 31

- Platin's (oxaliplatin) - Vincristine - Anti-angiogenesis agents (thalidomide)

Question 32

What are S&S of peripheral nervous system toxicities?

Answer 32

- Tingling/numbness distal end of extremities | - Burning sensation and unsteady on feet (changed prioproception d/t altered sensation)

Question 33

What is the most important preventative/management strategy for peripheral neuropathy?

Answer 33

* * Identify early and stop or alter the drug! These toxicities are often dose limiting, and it is crucial to recognize and stop to prevent further injury and to distinguish from nervous system involvement d/t other diseases - Temporary in most cases but it may take months to years to recover - Some cases cause permanent damage - Education re: what to monitor for - Safety precautions (eg. education for fall prevention if sensation decreased) - Assess for risk factors (pre-existing neuropathy from non-Ca causes, like DM or alcohol)

Question 34

What are risk factors for chemo-induced nephrotoxicity?

Answer 34

- Tumor-related kidney effects (eg. primary renal Ca; metabolic changes; volume changes) - Innate drug toxicity - Patient factors (older age, underlying AKI/CKD) and other nephrotoxic drugs they may be taking - Co-morbidities (eg. HTN)

Question 35

What causes nephrotoxicity?

Answer 35

- Acute renal failure if no pre-hydration with some drugs - Some drugs can cause renal failure with anemia and HTN - Necrosis of renal tubules, huge cause of CHF - High dose of drugs can gather in renal tubules and impair GFR (eg. methotrexate)

Question 36

What are preventative and management strategies for nephrotoxicity?

Answer 36

- Pre-hydration to increase urine flow - Mannitol (diuretic to force urine production) - Encourage + fluids at home, 2-3 L/day - Monitor labs and try to obtain baseline renal function - Monitor intake/output and weight changes

Question 37

What drugs cause nephrotoxicity?

Answer 37

- Cisplatin - Ifosfamide (AA) - Cyclophosphamide (AA) - Methotrexate