Treatment of Cancer: Surgery, Chemo & Radiation Flashcards Preview

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Flashcards in Treatment of Cancer: Surgery, Chemo & Radiation Deck (91):
1

What are the 4 phases of the cell cycle?

1. G1 phase: RNA & protein synthesis, cell growth, DNA repair
2. S phase: DNA completely replicated
3. G2 phase: additional synthesis of RNA, protein & specialized DNA
4. M phase: mitosis

2

Define the following:

1. Resting phase?

2. Growth fraction?

3. Generation time?

1. Resting phase
-cells do not engage in synthetic activities

2. Growth fraction
-proportion of cells in a tumor actively involved in cell division

3. Generation time
-length of a cell cycle

3

Chemotherapy Modes of Action
2

1. Cell cycle specific
2. Cell cycle nonspecific

4

Describe the followinig modes of action and in what situations they are most useful in:
1. Cell cycle specific
2. Cell cycle nonspecific

1. Cell cycle specific
-Kills in specific phase of cell cycle
-Most useful in tumors with large proportion of actively dividing cells

2. Cell cycle nonspecific
-Kills in all phases
-Useful in tumors with low growth index

5

Which medications work n the following phases of the cell cycle?
1. G2 phase? 1
2. Mitosis? 1
3. S phase? 4
4. G1 phase? 2
5. G0 state? 1

1. Bleomycin

2. Vinca Alkaloids

3.
-Antimetabolites
-Antifolates
-Antipyrimidines
-Antipurines

4.
-Asparaginase
-Actinomycin

5. Nitrosoureas

6

What are the phase nonspecific drugs? 3

1. Alkylating agents
2. Antitumor antibiotics
3. Cisplatin

7

1. What reasons do we treat cancer with surgery? 3

2. Systemic Chemotherapy: What are the different kinds? 4

3. What are the reasons we do radiation? 3

1. Surgery
-Definitive
-Staging
-Palliative

2. Systemic Chemotherapy
-Intravenous vs. oral
-Neoadjuvant vs. adjuvant

3. Radiation
-Definitive
-Salvage
-Palliative

8

Describe surgery meant for definitive treatment.


Describe surgery for palliatove treatment?

Definitive: treatment plan that has been chosen as the best one for a patient after all other choices have been considered

Palliative: relieving or soothing the symptoms of a disease without producing a cure

9

Systemic Chemotherapy is what?

Means of administration? 5

1. Type of cancer treatment using drugs to kill the cancer cells

2. Means of administration:
-Intravenously
-Injection
-Intraperitoneal
-Orally
-Topically

10

Classes of Chemotherapy Drugs
6

1. Alkylating agents
2. Antimetabolites
3. Mitotic inhibitors
4. Anthracyclines
5. Topoisomerase inhibitors
6. Miscellaneous

11

Alkylating Agents:
1. MOA?
2. Work in which phases of the cell cycle?
3. Used to treat many different cancers, including what? 8

1. Directly damage DNA to keep the cell from reproducing

2. Work in all phases of the cell cycle

3. Used to treat many different cancers, including:
-leukemia,
-lymphoma,
-Hodgkin’s disease,
-multiple myeloma, and
-sarcoma,
as well as cancers of the
-lung,
-breast, and
-ovary

12

Alkylating Agents:
Primary toxicities as a class?
4

Primary toxicities as a class
1. Nausea
2. Vomiting
3. Myelosuppression
4. Alopecia

13

Classes of Alkylating Agents
4

1. Nitrogen mustards
2. Platinum analogs
3. Tiazenes
4. Miscellaneous

14

Alkylating Agents: Nitrogen mustards are which ones? 3

1. Mechlorethamine (nitrogen mustard)
2. Cyclophosphamide (Cytoxan)
3. Ifosfamide (Ifex)

15

Cyclophosphamide (Cytoxan)….side effect?


What other drug can cause this?

Hemorrhagic cystitis


May also be caused by Ifosfamide (Ifex)

16

Describe how Hemorrhagic cystitis from Cyclophosphamide (Cytoxan) occurs?
2

1. Metabolic products of Cytoxan secreted into the urine
2. Bladder mucosa may become damaged

17

Bladder mucosa may become damaged from Hemorrhagic cystitis from Cyclophosphamide (Cytoxan). How will this manifest?
3


How can you prevent this?
1

1. May shed large segments of bladder mucosa
-Prolonged hematuria
2. May lead to urinary obstruction (due to clots)
3. If urine is concentrated may cause severe bladder damage


1. Need to increase fluid intake before and after infusion and empty bladder frequently

18

Alkylating Agents: Platinum analogues
3

Carboplatin (Paraplatin)
Cisplatin (Platinol)
Oxaliplatin (Eloxatin)

19

Cisplatin (Platinol)…side effects
2

1. Nephrotoxicity
2. Neurotoxicity

20

How can we prevent nephrotoxicity in Cisplatin pts? 2

What levels may be low from this drug? 3

1. Patients must be vigorously hydrated prior, during and after cisplatin administration
2. Monitor electrolytes and renal function

1. Low potassium,
2. sodium and
3. magnesium levels can be seen

21

How will neurotoxicity present in a pt taking Cisplatin? 2

How can we prevent this? 1

1. Peripheral neuropathy
-Painful parasthesias
2. Ototoxicity that can lead to deafness

1. Amifostine is given IV to protect against nephro/neurotoxicity from Cisplatin

22

Leukemia from Alkylating Agents:
1. Describe why this happens?

2. In rare cases it can lead to what?

3. The risk of leukemia from alkylating agents is dependant on what?

4. Risk of leukemia after getting alkylating agents is highest about _______ years after treatment

1. Because these drugs damage DNA they can cause long-term damage to the bone marrow

2. In rare cases leads to acute leukemia

3. The risk of leukemia from alkylating agents is dose-dependent

4. 5 to 10 years after treatment

23

Antimetabolites
1. MOA?
2. Work during what phase?
3. What are they commonly used to treat? 4

1. Interfere with DNA and RNA growth by substituting for the normal building blocks of RNA and DNA

2. Damage cells during the S phase, when the cell’s chromosomes are being copied

3. They are commonly used to treat:
-leukemias,
cancers of the
-breast,
-ovary, and
-the intestinal tract,

as well as other types of cancer

24

Primary antimetabolite toxicities
4

1. Myelosuppression
2. Nausea and vomiting
3. Mucositis
4. Dermatologic (rash, injection site reaction, dermatitis, pruritis)

25

Classes of antimetabolites
3

1. Folate antagonists

2. Purine analogs

3. Pyrimidine analogs

26

Name the specific drugs in each category of Antimetabolites:
1. Folate antagonists

2. Purine analogs

3. Pyrimidine analogs 2

1. Methotrexate (MTX, Trexall)

2. Mercaptopurine (6-MP, Purinethol)

3.
-Fluorouracil (5-FU)
-Gemcitabine (Gemzar)

27

Methotrexate (MTX; Trexall)
1. MTX toxicity mainly affects cells with what?

2. Such as? 2

3. Can damage what organs? 2

4. Sometimes high dose MTX is needed and what is given to reverse the toxic effects of MTX otherwise the patient may die?

1. Rapid turnover

2.
-Bone marrow (myelosuppression)
-Mucosa (mucositis)

3. Liver and kidney

4. Leucovorin (reduced folic acid)

28

-Methotrexate (MTX; Trexall)
Complications? 2

-Vigorous hydration and _________ loading prevent ______________________in the renal tubules?

-Drugs that impair MTX excretion? 7

1. Decreased renal clearance
-May need prolonged therapy with leucovorin
2. Effusions
-Will go into the effusions and leak out continuously and expose normal tissue to the drug

1. bicarbonate, crystallization of the urine


1. ASA,
2. NSAIDs,
3. amiodarone,
4. omeprazole,
5. PCN,
6. phenytoin,
7. sulfa compounds

29

Mitotic inhibitors
1. MOA?
2. Works in which phases?
3. AKA?
4. classes in this category? 4

1. Work by altering the DNA inside cancer cells to keep them from growing and multiplying

2. Work in all phases of the cell cycle

3. Also known as Anti-tumor
Antibiotics or Antimicrotubules

4. Classes
-Vinca Alkaloids
-Taxanes
-Epothilone
-Anthracyclines

30

1. Mitotic inhibitors are derived from what?

2. They work by stopping mitosis in the ___ phase of the cell cycle but can damage cells in ___ phases

3. How do they accomplish the above?

1. plant alkaloids and other compounds derived from natural products

2. M, all

3. keeping enzymes from making proteins needed for cell reproduction

31

Mitotic inhibitors: Toxicities?
3

Used to treat many different types of cancer including: 5

1. myelosuppression,
2. anaphylactic reactions,
3. peripheral neuropathy

1. breast,
2. lung,
3. myelomas,
4. lymphomas
5. leukemias

32

Mitotic inhibitors are what drug categories?
4

1. Taxanes:
2. Epothilones:
3. Vinca alkaloids:
4. Estramustine (Emcyt)

33

Which drugs are in the following Mitotic inhibitors?
1. Taxanes 2
2. Epothilones 1
3. Vinca alkaloids 3

1. paclitaxel (Taxol)
2. docetaxel (Taxotere)

1. ixabepilone (Ixempra)

1. vinblastine (Velban),
2. vincristine (Oncovin),
3. vinorelbine (Navelbine®)

34

Vinca Alkaloids
interfere with what phase?

M phase

35

Vincristine (Oncovin)…side effect?

Neuropathy

36

Neuropathy caused by Vinca Alkaloids:

1. Most commonly caused by which agent?

2. How can it manifest? 3

1. Vincristine (Oncovin)

2.
-Paresthesias in the fingers and toes (mild)
-Symptoms can move distal to proximal and result in significant weakness
-Constipation is the most common symptom of autonomic neuropathy

37

How can we treat constipation caused by Vincristine (Oncovin)?

Start on stool softeners at the beginning of therapy otherwise may progress to severe stool impaction

38

Which drugs are in the Anthracyclines drug category?
4

1. Daunorubicin (Cerubidine)
2. Doxorubicin (Adriamycin)
3. Idarubicin
4. Epirubicin

39

1. Anthracyclines…side effect?

2. What does it lead to?

Cardiotoxicity –

leading to systolic CHF

40

How can cardiotoxicity from Anthracyclines manifest?
3

1. Acute (during administration)
2. Subacute (days to months following administration)
3. Late (years following administration)

41

Risk factors for cardiotoxicity from anthracyclines?
4


Most commonly associated with what drug?

1. high cumulative dose (over a lifetime),
2. age > 70,
3. previous or current chest radiation,
4. cardiac disease


Most commonly associated with Doxorubicin (Adriamycin) (most commonly used anthracycline)

42

Anthracyclines…cardiotoxicity
1. What do you need to do before you start Anthracyclines therapy?

2. When should you continue and when should you discontinue therapy?

3. Long term follow up?

1. Effects may be irreversible
-Need a baseline nuclear medicine MUGA scan(multigated acquisition scan) to calculate EF

2.
-EF > 50% proceed
-EF less than 30% discontinue

3. Long term follow-up and monitoring for the development of CHF/cardiomyopathy is warranted

43

Topoisomerase inhibitors
1. MOA?
2. Topoisomerase inhibitors are grouped according to which type of enzyme they affect? 2

1. These drugs interfere with topoisomerases, which help separate the strands of DNA so they can be copied during the S phase

2.
-Topoisomerase I
-Topoisomerase II

44

Topoisomerase I and II inhibitors
1. Topoisomerase I inhibitors include? 2

2. Topoisomerase II inhibitors include? 3

1.
-Topotecan***
-Irinotecan (CPT-11)

2.
-Etoposide (VP-16)***
-Teniposide
-Mitoxantrone (also acts as an anti-tumor antibiotic)

45

Topoisomerase inhibitors
1. Used to treat what? 4
2. General toxicities? 3
3. Topoisomerase II inhibitors can increase the risk of a what?

1. Used to treat certain
-leukemias, as well as
-lung,
-ovarian,
-gastrointestinal, and other cancers

2. General toxicities
-Myelosuppression,
-alopecia,
-GI toxicity

3. Topoisomerase II inhibitors can increase the risk of a second cancer

46

Topoisomerase II inhibitors can increase the risk of a second cancer
1. What kind of cancer?
2. As early as what after the drug is given?

1. acute myelogenous leukemia (AML)
2. as early as 2 to 3 years after the drug is given

47

Miscellaneous agents
4 (what are the two most common)

1. Actinomycin-D
2. Bleomycin
3. Mitomycin-C
4. Mitoxantrone (also acts as a topoisomerase II inhibitor)

48

Bleomycin (Blenoxane)…side effects

4

1. Edema of the interphalangeal joints and hardening of the skin on the palms and soles of the feet
2. Anaphylactic or serum sickness like reaction
3. Pulmonary fibrosis
-Can be fatal
4. Hypotensive reaction
-Severe to fatal after the first dose in about 1% of patients

49

What symtpoms should we watch for to look for pulmonary fibrosis due to the Belomycin?
3

1. Watch for cough,
2. dyspnea,
3. infiltrates on X-ray

50

Other types of cancer drugs
4

1. Targeted therapies
2. Differentiating agents
3. Hormone therapy
4. Immunotherapy

51

1. Describe the advantage of targeted therapies?

2. What do the targeted therapies attack?
2

3. Used in what ways? 2

4. Most effective against what cancers? 4

1. Newer drugs that attack cancer cells more specifically than traditional chemotherapy drugs

2. Most attack
-cells with mutant versions of certain genes, or
-cells that express too many copies of a certain gene

3.
-Can be used as part of the main treatment, or
-they may be used after treatment to keep the cancer under control or keep it from coming back.

4.
-non-Hodgkin’s lymphoma,
-leukemia,
-lung cancer,
-breast cancer

52

Examples of targeted therapies include:
4 (most important)

1. Imatinib (Gleevec®)
2. Gefitinib (Iressa®)
3. Sunitinib (Sutent®)
4. Bortezomib (Velcade®)

53

Differentiating agents are what?

Examples? 3

These drugs act on the cancer cells to make them mature into normal cells

Examples
1. Retinoids, tretinoin (ATRA or Atralin®)
2. Bexarotene (Targretin®)
3. Arsenic trioxide (Arsenox®)

54

Hormone therapy
1. Drugs in this category are what?
2. They are used to slow the growth of what? 3
3. How do they work? 2

1. Drugs in this category are sex hormones: Change the action or production of female or male hormones

2. They are used to slow the growth of
-breast,
-prostate, and
-endometrial (uterine) cancers, which normally grow in response to natural sex hormones in the body

3.
-Work by making the cancer cells unable to use the hormone they need to grow,
-or by preventing the body from making the hormone

55

Examples of hormone therapy include:
6

1. Anti-estrogens
2. Aromatase inhibitors
3. Progestins?
4. Estrogens
5. Anti-androgens
6. Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH) agonists or analogs

56

Name the specific drugs in each category:
1. Anti-estrogens? 3
2. Aromatase inhibitors? 3
3. Progestins? 1
4. Anti-androgens? 3
5. Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH) agonists or analogs? 2

1.
- fulvestrant (Faslodex®),
-tamoxifen, and
-toremifene (Fareston®)

2.
-anastrozole (Arimidex®),
-exemestane (Aromasin®)
-letrozole (Femara®)

3. megestrol acetate (Megace®)

4.
-bicalutamide (Casodex®),
-flutamide (Eulexin®)
-nilutamide (Nilandron®)

5.
-leuprolide (Lupron®)
-goserelin (Zoladex®)

57

There are different types of immunotherapy: What are they and describe them? 2

1. Active immunotherapies stimulate the body’s own immune system to fight the disease

2. Passive immunotherapies do not rely on the body to attack the disease

58

Passive immunotherapies do not rely on the body to attack the disease: How do they work?
2

1. Immune system components (such as antibodies) created outside the body and given to fight the cancer

2. Man made monoclonal antibodies designed to attach to cancer cells and mark them for destruction by the immune system

59

What are checkpoint inhibitors?

Checkpoint inhibitors…new type of monoclonal antibody that works by blocking the signal that cancer cells send out telling the immune system not to attack. The drug allows the immune system to recognize the tumor
(passive immunotherapies)

60

Immunotherapies most effective against what? 3

1. melanoma,
2. kidney cancer,
3. lung cancer

61

Examples of active immunotherapies include?
3

1. Monoclonal antibody therapy,
2. Non-specific immunotherapies and adjuvants (other substances or cells that boost the immune response)
3. Immunomodulating drugs

62

What are the drugs that are associated with the following types of immunotherapies:
1. Monoclonal antibody therapy? 2
2. Non-specific immunotherapies and adjuvants (other substances or cells that boost the immune response)? 3
3. Immunomodulating drugs? 2

1. such as
-rituximab (Rituxan®)
-alemtuzumab (Campath®)

2. such as
-BCG,
-interleukin-2 (IL-2)
-interferon-alfa

3. , such as
-thalidomide
-lenalidomide (Revlimid®)

63

Chemotherapy Cycles
1. A cycle may involve what?

2. What does this give normal cells a chance to do?

1. A cycle may involve a dose of one or more drugs followed by several days or weeks without treatment
2. This gives normal cells time to recover from drug side effects

Sometimes, doses may be given a certain number of days in a row, or every other day for several days, followed by a period of rest. Some drugs work best when given continuously over a set number of days.

64

Chemotherapy Regimens
1. Adjuvant therapy?

2. Neoadjuvant therapy?

1. Adjuvant
-Set course given to patients with no evidence of disease after surgery or radiation

2. Neoadjuvant
-Aims at eradicating micrometastatic disease or reduce inoperable disease

65

Chemotherapy Regimens
1. Induction?

2. Maintenance?

1. Induction
-Combination chemotherapy given in high dose to cause a remission

2. Maintenance
Also called consolidation
-Long term, low dose regimen given in remission

66

How does maintance therapy maintain remission?

Maintains remission by inhibiting growth of remaining cancer cells

67

Radiation Therapy is what?

Radiation Therapy…. the use of high energy radiation from x-rays, gamma rays, neutrons, protons, etc. to kill cancer cells and shrink tumors

68

Ionizing radiation is the production of what?

free hydrogen ions and hydroxyl radicals

69

Determination of Dose

1. Tumors have individual radiobiologic characteristics
-Unique dose requirements for treatment
-Determined by multiple biologic studies done over time

70

Toxicity of Skin Radiation
3

1. Erythema
Onset: 4-14 days
Peak: 4-5 weeks
Resolves: 2-6 weeks after completion

2. Dry desquamation
Typically 5-6 weeks, earlier w/ accelerated RT or concurrent chemo
Resolves: 3-4 weeks after completion

3. Moist desquamation
Following 40-50 Gy (Gray Unit), trauma/excess friction, bolus, chemotherapy
Recovery 2-6 weeks after completion

71

Toxicity of Skin Radiation
1. Subacute?
2. Late manifestations? 3

1. Hyperpigmentation (as early as 2-3 weeks and usually resolves 3-12 mos)

2. Late:
1. Hypopigmentation in the treatment field
2. Telangiectasias
3. Fibrosis

72

Toxicity of Brain Radiation
1. Acute? 4
2. Late? 3

1.
-Fatigue
-Hair loss
-Erythema of the skin
-Desquamation

2.
-Cognitive dysfunction
-Edema
-Necrosis

73

Toxicity of Head/Neck Radiation
1. Acute 4
2. Late? 5

1. Mucositis
2. Taste dysfunction
3. Pain
4. Xerostomia (Can lead to dental caries)

1. Permanent Xerostomia
2. Soft tissue fibrosis
3. Osteoradionecrosis of the mandible
4. Dysphagia
5. Pharyngeal stricture

74

How does muscositis present?
3

1. Odynophagia
2. Dehydration
3. Weight loss

75

Toxicity of Breast Radiation
ACUTE
Common and Temporary
Signs and symtpoms?
6

1. Skin Redness 90%
2. Dry desquamation 30-50%
3. Moist desquamation 10%
4. Pain… OTC analgesics 25%
5. Pain… narcotics 9%
6. Fatigue 70%

76

Toxicity of Breast Radiation
LATE
Uncommon and Permanent
Signs and symtpoms?

7

1. Fibrosis 15%
2. Hyperpigmentation 10%
3. Cosmetic failure 15%
4. Rib fracture less than 0.1%
5. Pneumonia less than 0.5%
6. Cardiac less than 0.1%
7. Secondary malignancies less than 0.001%

77

Toxicity of Lung Radiation… Acute
4

1. Esophagitis
2. Cough

3. Skin Reaction
4. Fatigue

78

Esophagitis treatment as a complication of lung radation? 3

1. Mucosal anesthetics (viscous lidocaine)
2. Agents that coat the surface (suspension or liquid antacids)
3. Liquid analgesics

79

1. Cough treatment as a complication of lung radation?

2. Radiation pneumonitis?

1. Antitussives with or without codeine

2. Bed rest, bronchodilators & corticosteroids
-Antibiotics not indicated

80

Toxicity of Lung Radiation…Late
4

1. Radiation Pneumonitis
2. Pulmonary fibrosis
3. Esophageal stricture
4. Brachial Plexopathy
- superior tumors

81

Toxicity of Esophageal Radiation
1. Acute? 6

2. Late? 3

1. Esophagitis
2. Modest skin tanning (posterior)
3. Fatigue
4. Weight loss
5. Diarrhea
6. Nausea/vomiting

1. Esophageal stricture & stenosis (>60%pts)
2. Perforation
3. Pneumonitis - RARE

82

How will a perforation present?
4

1. Substernal chest pain
2. Elevated pulse
3. Fever
4. hemorrhage

83

Toxicity of Abdominal Radiation
Stomach, Pancreas, Hepatobiliary
1. Acute? 4
2. Late? 3

1. Dyspepsia (PPI to reduce acid)
2. Anorexia
3. Nausea (Prophylactic ondansetron (Zofran) prior to treatment)
4. Fatigue

1. Bowel obstruction
2. Worsening diabetes 2nd to worsening pancreatic function
3. Liver/kidney (Usually kept at safe doses, Renal failure, HTN)

84

Toxicity of Pelvic Radiation
1. Acute? 4

2. Late? 3

1. Diarrhea - common (Imodium, Lomotil)
2. Rectal irritation - RARE (Pain
and bleeding)
3. Urinary Sx
4. Fatigue

1. Persistent Urinary Sx (Frequency, Nocturia, Incontinence…stress)
2. Bowel changes
(Loose stools)
3. Erectile dysfunction

85

What urinary symptoms might you see from pelvic radation?
4

1. Freq/Urgency
2. Dysuria
3. Nocturia
4. Retention

86

Toxicity of Anal Radiation
1. Acute?6
2. Late?7

1. Skin reactions
-dry and/or moist desquamation
2. Leukopenia
3. Thrombocytopenia
4. Proctitis
5. Diarrhea
6. Cystitis

1. Chronic diarrhea
2. Rectal urgency
3. Sterility
4. Impotence
5. Vaginal dryness
6. Vaginal fibrosis
7. Possible decreased testosterone

87

Toxicity of GYN Radiation
6

1. Cystitis
2. Proctitis
3. Fistula (Rectovaginal
and Vesicovaginal)
4. Vaginal ulceration/necrosis
5. Vaginal stenosis
6. Skin reactions (rectal, anal, vulvar)

88

How would we treat skin desquamation from GYN radaiton?
3

Desquamation….
1. treat with hydration, domeboro soaks,
2. Silvadene and narcotic pain medication
3. Attempt to decrease dose to external genitalia to reduce skin reactions (groin & interglutteal clefts)

89

Toxicities are anatomically site specific… localized to irradiated tissue volumes
________ is the only systemic side effect

Fatigue

90

Degree of damage is dependent on the treatment regimen related factors
3

1. Types of radiation used
2. Total dose administered
3. Field size/fractionation

91

1. Late side effects caused by radiation should be a what?


-Explore other causes of symptoms
-Discuss with radiation oncologist who can look at the plan to verify radiation as cause

Chronic problems can occur

1. diagnosis of exclusion