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Cancer managment > Pharmacology of Anti-cancer drugs > Flashcards

Pharmacology of Anti-cancer drugs Flashcards

1
Q

At the end of the sessions, you will be able
to
• Identify the mechanism of action of major
classes of chemotherapy and targeted
agents
• Describe the common adverse effects of
these agents
• Discuss the strategies to prevent and/or
manage common toxicities of these agents

A

1

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2
Q

Anti-cancer drug are dosed based on _________ as it correlates better from animals models when doing inter-specie comparisons, which affects ________ and __________.

A
  1. body surface area (mg/m2)
  2. cardiac output
  3. renal clearance
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3
Q

The 8 main classes of chemotherapy agents include:

  1. _______ agents
  2. _______ inhibitors
  3. Anti-_______
  4. Anti-_______
  5. _______ therapies
  6. _______ therapies
  7. I_________
  8. Miscellaneous
A
  1. Alkylating
  2. Enzyme
  3. metabolites
  4. microtubules
  5. Endocrine
  6. Targeted
  7. Immunotherapies
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4
Q

Cell cycle specific agents preferentially kill what type of cells?

Cell cycle non specific agents kill both normal and malignant cells to what kind of extent?

A
  1. Cell cycle specific agents preferentially kill PROLIFERATING cells
  2. Cell cycle non specific agents kill both normal and malignant cells to the SAME extent (i.e. radiation)
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5
Q

For both cell cycle specific/ non-specific agents, _______ cells are more favored.

A

proliferating

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6
Q

For cell cycle specific agents, toxicity is the greatest during which phase?

What type of infusion administration improves cytotoxicity against cancer cells?

A

cell cycle specific agents: exert their toxic effect on proportion of cells in the part of the cell cycle in which the agent is active

  1. toxicity is the greatest during S phase of DNA synthesis
  2. Administering as CONTINUOUS INFUSION allows more exposure to more cells in the specific cycle
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7
Q

Which phases do Cell Cycle Non-Specific Agents Exert their cytotoxic effect?

Their cell kill is proportional to ____.

A
  1. Cell Cycle Non-Specific Agents Exert their cytotoxic effect THROUGHOUT the cell cycle, including the resting phase
  2. Their cell kill is proportional to DOSE
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8
Q

Cell Cycle Non-Specific Agents Agents include _________ agents, ___ antibiotics, antitumor antibiotics, ___ , altretamine.

A
  1. alkylating
  2. anthracycline
  3. nitrosoureas
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9
Q

Chemo drugs can cause acute toxicity by ___. Tissues with ___ i.e. bone marrow, GI mucosal cells, skin/hair are most affected, frequently leading to bone marrow suppression, mucositis, aloepecia and anaemia.

A
  1. inhibiting host cell division
  2. fast renewal cell populations

Cells that are rapidly dividing are most susceptible to acute toxicities

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10
Q

Chemo drugs can cause delayed toxicity such as __ and ___.

A
  1. infertility
  2. secondary malignancies
    (may be irreversible)

delayed toxicity: months to years after treatment

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11
Q

We should note the following delayed toxicities: ____-specific toxicity

___-induced cardiac toxicity and

Methotrexate-induced ___.

A

these are drug-specific toxicity

  1. Anthracycline
  2. pneumonitis (lung toxicity)
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12
Q

Alkylating agents include the following 6 classes:

  1. Alkyl ___
  2. Aziridines
  3. Hydrazine and Triazenes
  4. __ mustards
  5. N__
  6. __ analogues
A
  1. sulfonates
  2. Nitrogen
  3. Nitrosoureas
  4. Platinum
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13
Q

Alkylating agents work by generating an _____ which binds to _____ sites (-NH, -OH, -PO4, -SH groups), resulting in cross-linking and alkylation of DNA.

The _____ atom of guanine is highly susceptible to alkylation, and accounts for 90% of the alkylated sites in DNA

A
  1. positively charged carbonium ion (electrophilic carbocation)
  2. electron-rich nucleophilic sites
  3. N7
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14
Q

Alkylating agents can cause cytotoxic effect by:

  1. Inhibiting DNA __
  2. __ of DNA
  3. Strand __
A
  1. replication and transcription
  2. Mispairing
  3. breakage
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15
Q

Alkylators generally do not show __.

A

cross resistance

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16
Q

Generally, In general, the dose limiting toxicity (DLT) for alkylating agents is __

A

myelosuppression

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17
Q

Alkylating agents usually cause neutropenia with a nadir at __ days and recovery in __ days,
except for the __ class, which demonstrate delayed nadir and recovery.

A
  1. 6 to 10
  2. 14 to 21
  3. nitrosourea
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18
Q

Common toxicities for most alkylating agents include __(1)___, ____(2)____, __(3)_ and __(4)__ .

A
  1. mucositis
  2. chemotherapy induced nausea & vomiting (CINV)
  3. neurotoxicity
  4. alopecia
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19
Q

Long term toxicities for alkylating agents can include pulmonary ______, ____ and secondary __ (peak incidence approximately 4 years after treatment)

A
  1. fibrosis
  2. infertility
  3. leukemias
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20
Q

Cyclophosphamide is a __ that is __ in the liver.

A
  1. prodrug

2. activated

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21
Q

Cyclophosphamide is metabolized to __ (therapeutic cytotoxic effect) and __ (harmful cytotoxic effect).

A
  1. phosphoramide mustard (4-hydroxycyclophosphamide)

2. Acrolein

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22
Q

Acrolein is an impt metabolite of Cyclophosphamide as it can cause __ (more damaging on bladder than anywhere else). We need to give __ (mesna) to counteract this effect.
The effect of acrolein more pronounced in __.

A
  1. hemorrhagic cystitis
  2. radical scavengers
  3. ifosfamide
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23
Q

What dosage forms is Cyclophosphamide available?

What is the oral absorption % of Cyclophosphamide?
Should it be taken on empty stomach or taken with food?

A

50mg in sugar/film coated tablets and injection ROAs

> 75%
preferably taken w food to dec GI upset

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24
Q

How is Cyclophosphamide metabolised and excreted?

A

Metabolism mainly by microsomal enzymes in liver, cytochrome P450 (CYP) primarily CYP2B6

Excretion is primarily by enzymatic oxidation to active and inactive metabolites, which are mainly excreted by urine

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25
Q

Typical Cyclophosphamide doses (600-750 mg/m^2 ) are used for treatment of _(1)__ and __(2)__ cancer.

High doses (2 g/m^2 ) are used in (3).

A
  1. lymphomas
  2. breast
  3. bone marrow transplants
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26
Q

Toxicities of Cyclophosphamide include (1) (dose related), SIADH and (2) (rare, mostly when high doses are given/long term therapy). (3) may occur in high doses as well.

SE of __(4)__ and __(5)___ potential (>1g high moderate, <1g low moderate)

A
  1. Nausea and vomiting
  2. hemorrhagic cystitis
  3. Cardiac dysfunction
  4. myelosuppression
  5. emetogenic potential (substance that causes vomiting)
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27
Q

One way to counsel patient to reduce hemorrhagic cystitis is to __ and use the __.

A
  1. drink plenty of water

2. washroom frequently

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28
Q

Ifosfamide is an analogue of cyclophosphamide

that is activated in liver by __. It causes worse __ than Cyclophosphamide.

A
  1. CYP3A4

2. hemorrhagic cystitis

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29
Q

Ifosfamide is primarily excreted via the __ route.

A

renal

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30
Q

__ must be administered with ifosfamide, along with vigorous _______ with ______ liters of NS (saline) pre- and post-hydration.

A
  1. Mesna
  2. hydration
  3. 1.5-2
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31
Q

We should encourage patients on ifosfamide to increase __ and __.

A
  1. oral fluid intake

2. frequent voiding of urine as much as possible

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32
Q

Ifosfamide can cause Nausea and Vomiting, __Toxicity, __ and is Dose limited by __.

A
  1. CNS
  2. Nephrotoxicity
  3. hemorrhagic cystitis
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33
Q

Platinum analogues are alkylating like agents which form a ____.
1st gen example: __
2nd gen example: __
3rd gen example: __

A
  1. reactive electrophile that covalently binds to DNA
  2. Cisplatin
  3. Carboplatin
  4. Oxaliplatin
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34
Q

Cisplatin is indicated for a wide range of __. The dose limiting toxicity for Cisplatin is __.

A
  1. solid tumors
  2. acute and delayed CINV (cisplatin is the most emetic drug = alot of vomitting; thus strong anti-emetic drugs are given along with cisplatin)
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35
Q

It is recommended to verify any dose of Cisplatin exceeding ___ and its use is not recommended if SCr < __ mg/dL.

A
  1. 100mg/m^2/cycle

2. 1.5 (mild CKD)

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36
Q

Vigorous hydration with adequate urine flow rate is required for administration of __.
Prehydration and post hydration with KCl & Mg SO4 are required due to __.

A
  1. Cisplatin

2. electrolyte wasting effects

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37
Q

Cisplatin nephrotoxicity is characterized by deterioration of renal function and __. We can prevent this by:
• Hydration w/ at least 1-2 L IV __ pre- and concurrent with cisplatin, with __ supplementation
• Maintain urine output >__ ml/h
• Provide ___ and/or ___
• Prolong __
• Give the patient __

• Avoid in patient with ___ dysfunction: do not use if CrCl less than ___ml/min

A
  1. electrolyte wasting
  2. Normal saline
  3. K & Mg
  4. 100
  5. mannitol (hydration protocol)
  6. furosemide (loop diuretic)
  7. infusion time ( e.g. 24 hour infusion)
  8. Amifostine
  9. renal
  10. 30
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38
Q

An alternative for cisplatin use in patients with renal dysfunction is __.

A

carboplatin

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39
Q

Amifostine is a radical scavenger that may __ efficacy of Cisplatin. It is __, can be __ and is less commonly used than switching to carboplatin.

A
  1. reduce
  2. expensive
  3. myelosuppressive
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40
Q

Cisplatin may cause (1) (may be reversible) with 50% frequency after a cumulative dose of (2) mg/m^2.

Solution:
- The strategy of __(3)_____ dose/ __(4)___ to carboplatin may reduce both efficacy and side effects. Symptomatic relief is an option as well.

  • Limit ___(5)___ doses

Medications to reduce __(6)____ pain: _(7)___, ____, ____

Cisplastin can be an _(8)____ to veins

A
  1. peripheral neuropathy
  2. 300-500
  3. reducing dose
  4. Substituting to carboplatin
  5. cumulative
  6. neuropathic
  7. gabapentin, amitriptyline, pyridoxine
  8. irritant
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41
Q

Cisplatin may cause __ (may be irreversible), which is related to __ peak doses. Patients often complain of being unable to __.

A
  1. ototoxicity
  2. high
  3. to hear high pitch sounds
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42
Q

___ employs a unique dosing based on the Calvert equation, where Dose = AUC X (GFR + 25). (AUC = 2 for wkly dosing, AUC = 5/6 for 3 wkly).

(Dose based on target area under curve, BSA not usually used)

A

Carboplatin

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43
Q

Carboplatin has a much lower incidence of __ , ototoxicity and ___ compared to to cisplatin. However, carboplatin can cause __ reactions.

A
  1. nephrotoxicity
  2. delayed Nausea and vomiting
  3. hypersensitivity
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44
Q

Carboplatin is indicated for a wide range of solid tumors (esp _____) but is dose limited by __ (especially __).

A
  1. ovarian
  2. myelosuppression
  3. Thrombocytopenia
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45
Q

__ is stable in D5W only (NOT saline). It is indicated for the treatment of __.

A
  1. Oxaliplatin

2. colorectal cancer

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46
Q

Oxaliplatin causes reversible ___ (often exacerbated by cold air). Compared to cisplatin, oxaliplatin shows much less __. Other toxicities include myelosuppression (much less than cisplatin) and __.

A
  1. cumulative peripheral neuropathy
  2. nephrotoxicity
  3. hypersensitivity
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47
Q

Enzyme inhibitors used in chemotherapy include Topoisomerase I inhibitors i.e. Irinotecan (Camptosar) that work by __ and Topoisomerase II inhibitors i.e. anthracyclines such as doxorubicin (Adriamycin) that work by __.

A
  1. cleavage of single strand DNA

2. Form a complex and cause double strand DNA breaks

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48
Q

Irinotecan (CPT-11) and its (even more) active metabolite SN-38 both bind to the Topoisomerase I-DNA complex, preventing __ , which ultimately leads to DNA breakage and death. It is cell cycle __ specific.

A
  1. re-ligation

2. S-phase

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49
Q

Irinotecan is indicated for the treatment of __ and is excreted via __.

A
  1. metastatic colorectal cancer

2. bile and urine

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50
Q

Irinotecan is dose limited by __ (both early: within 1st 24h and late: >24h) which can be managed using high doses of loperamide until the patient is __.

A
  1. Diarrhoea
  2. diarrhoea free for 12h

4mg at earliest sign of diarrhoea, followed by 2mg PO q2h until diarrhoea free for 12h

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51
Q

Cholinergic syndrome can occur with use of __, characterized by SLUD, which stands for __. We can prevent this with 0.25-1mg SC/IV __.

A
  1. Irinotecan
  2. Salivation/Sweating, Lacrimation, Urination, Diarrhoea
  3. Atropine
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52
Q

UGT1A1 undergoes conjugation reactions with __.
For patients with UGT1A1 deficiency demonstrate exceptional toxicity with use of __. A reduction of starting dose by at least 1 dose level if UGT1A1*28 homozygosity is detected.

A
  1. SN-38
  2. Irinotecan

1 dose level: 25% decrease

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53
Q

Etoposide is indicated for a wide range of __ and is available as __ or __ ROA. The __ (ROA) dose is twice greater than __ (ROA) dose.

A
  1. solid tumors
  2. PO (caplet)
  3. IV (injection)
  4. PO
  5. IV
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54
Q

Etoposide is dose limited by __ and __ (when infusions are given too quickly).

A
  1. Myelosuppression (primarily neutropenia)

2. Hypotension

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55
Q

Etoposide IV infusions should be given over a minimal duration of 1hr (usually 2hr) to avoid __ and the concentration should not exceed 0.4 mg/ml to avoid __. Use of non-PVC tubing is encouraged due to __.

A
  1. hypotension
  2. precipitation of infusion
  3. the use of polysorbates as diluents
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56
Q

Anthracyclines have 3 MOAs:

  1. Induce formation of __
  2. __ between base pairs in the DNA (similar to alkylators)
  3. Metabolism in the liver to form __ (unique MOA).
A
  1. covalent topoisomerase II DNA complexes - this inhibition prevents the religation of DNA during DNA replication causing DNA strand breaks
  2. Intercalations
  3. oxygen free radicals
57
Q

Anthracyclines are dose limited by __ and all of them can cause __. As a result, patients should have a __ performed prior to use.

A
  1. myelosuppression (primarily neutropenia)
  2. cardiotoxicity
  3. baseline MUGA / ECHO
58
Q

Ladies may not prefer __ or __ due to the side effect of alopecia.

A

anthracyclines

vinca alkaloids

59
Q

Anthracyclines can cause acute N and V and __ (we should counsel patients not to be alarmed). They are also __ (related to extravasation which may be avoided by using central lines).

A
  1. red discoloration of urine
  2. vesicants

(Extravasation refers to the leakage of injected drugs from blood vessels causing damage to the surrounding tissues)

60
Q

Anthracycline cardiotoxicity can manifest as __ (Acute, within 24 hours), __ (Subacute, within weeks to months) and __ (Late, > 5 years).

A
  1. arrhythmias and Pericarditis
  2. Tachycardia
  3. Cardiomyopathy
61
Q

Risk factors for Anthracycline cardiotoxicity include:

  1. __ doses
  2. Administration schedule (__)
  3. Age
  4. __
  5. Known cardiac disease

CAAMK

A
  1. Cumulative
  2. high peaks
  3. Mediastinal radiation (radiations to the chest area)
62
Q

Anthracycline cardiotoxicity can be prevented by:

  1. __
  2. altering the administration schedule via ___ doses and ___.
A
  1. Limiting cumulative dose
  2. fractionate
  3. prolonging infusion time
63
Q

The use of less cardiotoxic anthracyclines and analogues has caveats. Mitoxantrone is included in __ while Liposomal doxorubicin (Caelyx®) is __.

A
  1. a limited number of cancer protocols

2. expensive

64
Q

The use of Dexrazoxane (cardiac protectant) to prevent anthracycline cardiotoxicity is not preferred as it is __, hard to administer and causes __. It is better to switch to another drug instead.

A
  1. extremely expensive

2. myelosuppression, N and V.

65
Q

Patients should have a __ to evaluate LVEF prior to starting therapy. If their LVEF is < __%, anthracyclines should not be started.

A
  1. baseline MUGA

2. 40

66
Q

Anti-metabolites work by __ i.e. Antifolate Agents (Methotrexate).
They may be __ i.e. Analogues (Purine and Pyrimidine)

A
  1. competing for binding sites on enzymes

2. incorporated directly into DNA or RNA

67
Q

Methotrexate can be used for many __ tumors and is available in ___ dosage forms. It is given over __ doses.

A
  1. solid and liquid (ALL, breast, head, neck, GVHD prophylaxis)
  2. Intravenous, Intrathecal or Oral
  3. a wide range of
68
Q

The main dose limiting toxicity for MTX is __. Other side effects include: nephrotoxicity, mucositis, diarrhea, hepatitis, pulmonary pneumonitis, central nervous system toxicities

A
  1. myelosuppression
69
Q 
\_\_ excretion can be affected by the following drugs: (DDI):
• NSAIDs
• Penicillin
• Ascorbic acid (Vitamin C)
• Probenecid, Sulfonamides
• Salicylates
• Omeprazole
A

Methotrexate

70
Q

Methotrexate works by __ (which converts folic acid to tetrahydrofolate). This results in a deficiency of __ and therefore a decrease in DNA synthesis, repair and cellular replication.

A
  1. irreversibly binding to dihydrofolate reductase DHFR

2. thymidylate and purines

71
Q

High dose methotrexate therapy (>1 g/m^2 ) require __ and __ until methotrexate levels are less than 0.1uM.

A
  1. therapeutic drug monitoring

2. folinic acid rescue

72
Q

MTX escapes into 3rd spaces, hence patients with __ are at higher risk for methotrexate toxicity with increased accumulation and slower elimination.

A

ascities or pleural effusions

73
Q

Cytarabine ( ara c), Gemcitabine ( Gemzar ®), 5 Fluorouracil (5 FU) and Capecitabine ( Xeloda ®) belong to the __ class of chemotherapy agents. They work by __.

A
  1. Pyrimidine analogues

2. inhibiting synthesis of DNA/RNA (thymidate synthase)

74
Q

5-FU toxicity depends on __ of treatment and/or __ of administration.

A
  1. duration

2. rate

75
Q

With bolus 5-FU administration, the dose limiting effects are __, __ and __.

A
  1. leucopenia
  2. thrombocytopenia
  3. anemia
76
Q

With continuous 5-FU infusion, the dose limiting effects is __ and __.

A
  1. Hand-foot syndrome Palmar Plantar Erythrodysethesias [PPE]
  2. diarrhea
77
Q

Additional toxicities of 5-FU include:

  • skin discoloration
  • nail changes
  • __ (requires sunscreen)
  • __ toxicity (numbness at tips of fingers)
  • __ (from vessel spasms)
A
  1. photosensitivity
  2. neurologic
  3. vasospastic angina
78
Q

5-FU may not be preferable for female patients as it can cause irreversible ___. This can be minimized through ___.

A
  1. skin pigmentation and freckles

2. using sunscreen and avoiding midday sun

79
Q

Capecitabine is an ___ of fluorouracil that is designed to be selectively activated by tumor cells due to the __ found in tumor cells. This minimizes systemic exposure of the active drug.

A
  1. orally active prodrug

2. higher proportion of thymidine phosphorylase (TP)

80
Q

Capecitabine is indicated for mainly __ and is available in ___ ROA. It is mainly excreted via the __ route.

A
  1. solid tumors (e.g. colorectal, breast)
  2. oral tablets
  3. renal
81
Q

Explain why Capecitabine patients may be less advantageous as compared to 5-FU for cancer patients?

A
  1. 5-FU is injectable, forces patients to come to the clinic for their injections, ensuring compliance
  2. it is easier to titrate 5-FU (injectable) vs Capecitabine which comes in fixed oral dosages (150/300mg)
82
Q

Capecitabine mimics the continuous infusion toxicities of 5-FU, and is dose limited by ___ (capecitabine > fluorouracil), ___ and __.

A
  1. hand foot syndrome
  2. diarrhea
  3. mucositis
83
Q

Additional toxicities of Capecitabine include __, ___ and __ (dry skin conditions possible as well).

A
  1. CINV
  2. fatigue
  3. rash

note: more of nausea > vomitting

84
Q

Anti-microtubules such as Colchicine and vinca alkaloids work by binding to ___, which inhibits formation of microtubules via ____ of tubulin.

A
  1. alpha and beta subunits of tubulin

2. polymerization

85
Q

A key benefit of vinca alkaloids is that they have __, meaning __ are not required.

A
  1. very low emetogenic potential

2. anti-emetics

86
Q

Vinca alkaloids can cause side effects such as __ and are __ , similar to anthracyclines.

A
  1. alopecia

2. vesicants

87
Q

Vincristine in particular, causes __, with doses limited to 2mg weekly. It can also cause ____ as well, but rarely causes __, which is an advantage over Vinblastine and Vinorelbine.

A
  1. Peripheral neuropathy
  2. ileus and constipation
  3. bone marrow suppression
88
Q

Vinblastine and Vinorelbine are both dose limited by __, which is why we must check the patient’s ___ before administering. They cause lesser __ and __ compared to Vincristine.

A
  1. Neutropenia and Thrombocytopenia
  2. blood profile
  3. neurologic toxicity and constipation
89
Q

Anti-microtubules such as taxanes bind preferentially to ____, stabilizing against __. They are used for many ___ cancer types.

A
  1. microtubules
  2. depolymerization
  3. solid (e.g. ovary, breast)
90
Q

Paclitaxel (Taxol®, Anzatax®) requires pre-medications to prevent __. The pre-meds include __. The ___ formulation of Paclitaxel does not require pre-medication.

A
  1. Hypersensitivity
  2. H1 blockers, H2 blockers and corticosteroids
  3. Albumin stabilized nanoparticle version (Abraxane®)
91
Q

Docetaxel (Taxotere®) requires PREMEDICATIONS for prevention of __ (caused by ___). __ should be started on the day before chemo.

A
  1. Edema
  2. Polysorbate formulation
  3. Dexamethasone
92
Q

Paclitaxel (Taxol®, Anzatax®) is dose limited by __ and also causes 15 to 21 days), __, myalgias, __ reactions and mucositis (seen more with prolonged infusions for 3 to 4 days), and ______ (IMPT)

A
  1. myelosuppression
  2. peripheral neuropathy
  3. hypersensitivity
  4. Alopecia, thus women prefer docetaxel
93
Q

Docetaxel (Taxotere®) is dose limited by __ and shows when compared to paclitaxel with less __, __ and asthenia compared to paclitaxel. In Asian populations, Docetaxel shows increased __.

A
  1. neutropenia
  2. peripheral neuropathy
  3. hypersensitivity reactions
  4. Myelosuppression
94
Q 
Endocrine therapies for cancer treatment include:
1. \_\_
• Selective Estrogen Receptor Modulators (SERMs)
• Pure antiestrogens
2. \_\_ 
• Nonsteroidal inhibitors
• Steroidal inactivators
3. LHRH agonists
4. Anti androgens
A
  1. Antiestrogens

2. Anti aromatase agents

95
Q

__ is preferable for breast cancer treatment in Pre-menopausal women while Post-menopausal women may be treated with ____ or _. In __ women, the aromatization pathway that produces most estrogen, compared to the ovaries in __ women.

A
  1. Tamoxifen
  2. preferably aromatase inhibitors or Tamoxifen
  3. Post-menopausal
  4. Pre-menopausal
96
Q

Tamoxifen is a SERM that works by __, blocking estrogen stimulation for cancer cells. It is indicated for treatment of estrogen receptor positive breast cancer
and is also effective in advanced endometrial cancer (THIS IS FOR OFF-LABEL USE; to ignore the endometrial cancer part.

A

inhibiting nuclear binding of estrogen receptor

97
Q

Tamoxifen exhibits ___. In breast epithelial cells, Tamoxifen is __ while in __/__/__, Tamoxifen is agonistic. The concern for agonistic activity at the endometrium is that Tamoxifen __. (To monitor)

A
  1. tissue specific activity
  2. antagonistic
  3. Bone/lipid/Endometrium
  4. may increase risk for endometrial cancer
98
Q

Aromatase inhibitors work by __ (the catalyst for __). Currently, 3 products are available on the market:
• Anastrozole (Arimidex®)
• Letrozole (Femara®)
• Exemestane (Aromasin®)

A
  1. inhibiting Aromatase

2. the last step in the aromatization pathway

99
Q

There is a need to supplement patients on Aromatase inhibitors with __ and __ to avoid __.

A
  1. Ca
  2. Vitamin D
  3. Bone loss
100
Q

The adrenal gland, muscles and fat all produce androgens for conversion to estrogen via aromatase enzyme. Hence it makes sense that Aromatase inhibitors can cause side effects such as __, __ and ___/__.

A
  1. fatigue
  2. hot flashes
  3. Myalgia/Arthralgia
101
Q

FDA considers targeted therapy as a drug __ that must be performed for the patient to be eligible to receive the drug. Therefore, Capecitabine __ targeted therapy despite its preferential activity in cancer cells.

A
  1. with a reference to a diagnostic test

2. is not considered

102
Q

__ may be an issue with Targeted therapies when patients __ (when they suffer side effects), compromising efficacy compared to traditional chemotherapy agents administered in clinics. They are also typically very expensive.

A
  1. Adherence

2. self-moderate drug intake

103
Q

Targeted therapies have many __. One example is Gefitinib CYP3A4 metabolism (i.e. ___ can increase plasma levels due to CYP3A4 inhibition). We need to keep a lookout by reading literature.

A
  1. Drug-Food and Drug-Drug interactions

2. grapefruit juice

104
Q

The __ of most Targeted therapies are not known as they have only entered the market for less than a decade. __ is required.

A
  1. Long term toxicities

2. Pharmacovigilance

105
Q

Targeted therapies have both __ and __ biomarkers for efficacy. A rash for Gefitinib may show patient is responding well to drug (despite being a troubling side effect). __ and __ are responsible for variable toxicity and response in targeted therapies.

A
  1. positive
  2. negative
  3. Pharmacogenomics
  4. Biomarkers
106
Q

Epidermal Growth Factor Tyrosine Kinase Inhibitors such as Gefitinib (Iressa®), Erlotinib (Tarceva®), Afatinib (Gilotrif®) are used in Lung and Pancreatic Cancer (__ only). Patients must test __ before EGFTKIs can be given.

A
  1. erlotinib

2. positive for EGFR

107
Q

EGFTKIs can cause GI side effects similar to __. This can be managed using loperamide: 2 tabs on onset, 1 every 2-4 hrs until diarrhea free for 12h. Other side effects include: __.

A
  1. Irinotecan

2. Dermatological toxicities

108
Q

EGFTKIs bind to the __ of protein tyrosine kinases, blocking __ , inhibiting cell proliferation. They may be used to enhance efficacy of Chemotherapy and radiotherapy.

A
  1. Intracellular portion

2. intracellular signals

109
Q

Supportive treatments (typically for __ side effects) administered for patients on EGFR inhibitors should __

A
  1. dermatological

2. not interfere with the anti-tumor effects of EGFR inhibitors.

110
Q

Targeted therapies should be easy to __, provide rapid __ to ensure good __. It is important to __ the therapy according to clinical presentation so we can minimize the side effects of therapy.

A
  1. administer
  2. results
  3. patient compliance
  4. individualize
111
Q

Monoclonal antibodies have a unique naming nomenclature.

  • __ refer to 100% mouse protein mAbs
  • __ refer to 34% mouse protein mAbs
  • Zumabs refer to __% mouse protein mAbs
  • Mumabs refer to __ % mouse protein mAbs
A
  1. Momabs
  2. Ximabs
  3. 10
  4. 0
112
Q

The higher the % of human protein, the lower the % chance for patients to develop __ (less likely to require pre-medication). Therefore, __ and __ usually do not require pre-medication.

A
  1. hypersensitivity
  2. Zumabs
  3. Mumabs
113
Q

Rituximab is available in IV and SC. Rituximab targets B cells in non-hodgkin lymphoma (CD20 molecules on cell surfaces) and can result in apoptosis via various ways.

  1. cell lysis via __ (ADCC)
  2. cell lysis via __ activation via MAC
  3. direct apoptosis
A
  1. Antibody dependent cell mediated cytotoxicity

2. complement

114
Q

Rituximab has __ (fever, chills/rigors, bronchospasm, hypotension). The __ has a higher incidence of infusion related reactions which is why we __. Therefore, it is important to pre-medicate with __ and __ alongside close monitoring.

A
  1. infusion related reactions
  2. 1st infusion
  3. give it slower
  4. Paracetamol and diphenydramine
115
Q

Nausea and vomiting, infection and myelosuppression are uncommon side effects for __.

116
Q

Bevacizumab (Avastin®) is a __ (VEGF) inhibitor used in Colorectal, lung and kidney cancer. Pre-medication is __.

A
  1. Vascular endothelial growth factor

2. not required

117
Q

Bevacizumab (Avastin®) should be avoided in patients who are __ or __. We should watch out for hypertension, __ (need to check before each administration) and risk of stroke. It should be temporarily suspended in __ and discontinued in __.

A
  1. at high risk for bleeds
  2. CNS metastasis
  3. proteinuria
  4. moderate proteinuria
  5. nephrotic syndrome
118
Q

VEGF is a signaling protein that promotes the growth of new blood vessels. VEGF forms part of the mechanism that restores the blood supply to cells and tissues when they are deprived of oxygenated blood due to compromised blood circulation.
Therefore, it makes sense that Bevacizumab (Avastin®) should not be used in patients with serious __, at risk from __ events, recovering from __, and suspected gastrointestinal __.

A
  1. hemorrhage
  2. thrombotic
  3. surgery (due to impeded wound healing)
  4. perforations
119
Q

Trastuzumab (Herceptin®) is a __ receptor antagonist used for Therapeutic Use: Breast cancer ad Gastric Cancer (if __). It is available in both IV and SC forms.

A
  1. HER2/Neu

2. HER2+

120
Q

Trastuzumab (Herceptin®) can lead to cardiotoxicity and __ (rare). The package insert recommends pre-medication with __ (unexpected as ___).

A
  1. hypersensitivity
  2. paracetamol
  3. herceptin is a -zumab (10% mouse protein with low chance for hypersensitivity)
121
Q

There is a wide variety of Immunotherapies. They can be __ (act on tumor) which includes anti-tumor mAbs. They can also be __ (act on immune system) which includes cytokines, therapeutic cancer vaccines and immuno-oncology therapies (i.e. checkpoint inhibitors and co-stimulatory agonists)

A
  1. Passive

2. Active

122
Q 
Immunotherapies can target normal organs as well, leading to immune related adverse events. 
Brain: \_\_
Thyroid: \_\_
Kidney/adrenal gland: \_\_
GI: \_\_
Skin: \_\_
Lungs: \_\_
Liver: \_\_
Pancreas: \_\_
Nerves: \_\_
Joints: \_\_
A 
Brain: Hypophysitis
Thyroid: Thyroiditis
Kidney/adrenal gland: Adrenal insufficiency
GI: Colitis
Skin: Dermatitis/Rash
Lungs: Pneumonitis
Liver: Hepatitis
Pancreas: Pancreatitis
Nerves: Motor and sensory neuropathies
Joints: Arthritis
123
Q

IPILIMUMAB (YERVOY®) blocks __, and allows the CTLs to destroy the cancer cells. It is Indicated for treatment of melanoma, NSCLC. Colorectal and hepatocellular carcinoma

A

the Cytotoxic T Cell Lymphocyte associated Antigen (CTLA 4) inhibitory signal

124
Q

IPILIMUMAB (YERVOY®) causes immunological related side effects: __, __ and __.

A

rash, diarrhea and thyroid

125
Q

__ (Programmed Cell Death) is an inhibitory signaling receptor expressed on activated T cells. Cancer cells can express __ to prevent T cells from destroying it.

A
  1. PD-1

2. PD-L1

126
Q

PD-1 inhibitors include:
• P___ (Keytruda®)
• N___ (Opdivo®)
• C___ (Libtayo®)

A
  1. Pembrolizumab
  2. Nivolumab
  3. Cemipilimab
127
Q

PD-L1 inhibitors include:
• A__ (Tecentriq®)
• D__ (Imfinzi®)
• A__ (Bavencio®)

A
  1. Atezolizumab
  2. Durvalumab
  3. Avelumab
128
Q

Interestingly, if a patient given Immunotherapy experiences __ (mild fevers and chills), infusion related reactions or some arthralgias (fatigue is common), they are considered __.

A
  1. flu-like symptoms

2. to be tolerating immunotherapy well

129
Q

What are the possible regimen for ifosfamide?

A
  1. VIP regimen for testicular cancer

2. RICE regimen for diffuse large B-cell lymphoma

130
Q

what is the presentation of neurotoxicity developed with the use of ifosfamide

A
  1. hallucination
  2. confusion
  3. somnolence
  4. sx usually begin 2-5 days after start of ifosfamide
131
Q

the accumulation of _________ is the cause of ifosfamide induced neurotoxicity

A

chloroacetaldehyde

132
Q

how do we prevent neurotoxicity with ifosfamide?

A
  1. caution in elderly patients
  2. caution w renal dysfunction
  3. increase infusion time
  4. avoid concurrent CNS active drugs
  5. decrease dose or discontinue treatment with onset of sx
  6. Methylene blue = inhibits MAO metabolism to chloroacetaldehyde
133
Q

5-FU is degraded in the liver by _______

A

dihydropyrimidine dehydrogenase (DPD)

134
Q

how is 5-FU excreted?

A

60-80% excreted as respiratory CO2
and
urine

135
Q

what is the recommendation on how to take capecitabine

A

taken within 30min after a meal

136
Q

MOA of 5-FU

A

converts into uracil, acts as a pyrimidine antagonist which prevent formation of DNA base thymidine

137
Q

use of BCR/ABL: _______ (Glivec), ________ (Spyrcel), ________ (Tasigna) are used for chronic myelogenous __________; acute lymphoblastic leukemia (Philadelphia chromosome +); _______ stromal tumor (GIST)

A
  1. Imatinib
  2. dasatinib
  3. nilotinib
  4. leukemia
  5. gastrointestinal
138
Q

what are the toxicities of BCR/ABL tyrosine kinase?

A
  1. N/V
  2. dose limiting myelosuppression
  3. fluid retention
  4. LFTs increase
139
Q

what are some drug classes that can be given for the dermatological toxicities of EGFTKI?

A
  1. anti-microbial
  2. corticosteroid/ immmunomodulators
  3. Emollient/Skin protectant
  4. Anti-histamine
  5. retinoids

Cancer managment (4 decks)

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