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Pharmacotherapeutics > Clinical Pharmacology of Anti-Cancer Agents (Part 2) > Flashcards

Clinical Pharmacology of Anti-Cancer Agents (Part 2) Flashcards

1
Q

Antimetabolites (Pyrimidine analogue)

  1. Types
  2. MOA
A
  1. 5-Fluorouracil, capecitabine

2. Incorporated into DNA and RNA, inhibits synthesis.

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2
Q

5-Fluorouracil

  1. MOA
  2. Toxicity
A
  1. Analogue of the pyrimidine uracil, thus acts as a pyrimidine antagonist.
  2. Toxicities include:
    - dose-limiting thrombocytopenia, leucopenia, anemia
    - dose-limiting hand-foot syndrome and diarrhoea
    - skin discoloration, nail changes, photosensitivity
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3
Q

Capecitabine

  1. Indication
  2. MOA
  3. Dose and dosing precaution
  4. Toxicity
A
  1. colorectal and breast cancer
  2. selectively activated by tumour cells
  3. Dose: 1250mg/m2 twice daily for 2 weeks, every 21 days. Recommended to be taken with food.
  4. Dose-limiting: hand-foot syndrome, mucositis, diarrhea. Additional toxicities: CINV, fatigue, rash
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4
Q

Spindle poisons MOA

A

A. Inhibit polymerization

  • Vinca alkaloids
  • Colchicine

B. Inhibit depolymerization
- Taxanes

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5
Q

Vinca-induced toxicities

A

A. In general

  • all very low emetogenic potential
  • vesicants
  • alopecia

B. Specific to Vincristine (more neurologic, constipation)

  • peripheral neuropathy: maximum dose is 2mg weekly
  • constipation

C. Specific to Vinblastine and Vinorelbine (more hematological)

  • dose-limiting neutropenia and thrombocytopenia
  • less neurologic toxicity and constipation than vincristine
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6
Q

Premedications required for taxanes

A
  1. Paclitaxel
    - premedication for prevention of hypersensitivity: H1 blocker, H2 blocker, corticosteroids.
    - abraxane: no premed
  2. Docetaxel
    - premedications for prevention of edema
    - dexamethasone starting on the day before chemo
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7
Q

Toxicities for Paclitaxel vs Docetaxel

A

Paclitaxel: more on myelosuppression, more peripheral neuropathy, hypersensitivity

Docetaxel: more neutropenia, less peripheral neuropathy and hypersensitivity

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8
Q

Treatment of breast cancer principles

A

Tamoxifen: premenopausal and postmenopausal diagnosis, can be used to treat both premenopausal and postmenopausal diagnosis
Aromatase inhibitor: postmenopausal diagnosis

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9
Q

Tamoxifen:

  1. drug class
  2. MOA
  3. indication
A
  1. Selective estrogen receptor modulators
  2. Inhibit nuclear binding of estrogen receptor, block estrogen stimulation of breast cancer cells
  3. Indicated for estrogen-receptor positive breast cancer, and advanced endometrial cancer
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10
Q

Aromatase inhibitors:

  1. MOA
  2. Medications
  3. Side effects
A
  1. inhibit the conversion of androgens to estrogens
  2. anastrozole, letrozole, exemestane
  3. Side effects: fatigue, hot flashes, arthralgia, bone loss (complement with calcium and vit D).
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11
Q

What is targeted therapy?

A
  • targeted therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules associated with tumour growth and progression.
  • diagnostic test must be performed for a patient to be eligible to receive the drug.
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12
Q

Types of EGFR and VEGFR inhibitors

A

EGFR:
- afatinib, erlotinib, gefitinib
VEGFR:
- vandetanib

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13
Q

EGFR:

  1. MOA
  2. Therapeutic uses
  3. Toxicities
A
  1. Decrease cell proliferation, cell survival time, angiogenesis, growth factors, metastasis. Increase chemotherapy and radiotherapy sensitivity.
  2. Lung cancer, pancreatic cancer (erlotinib only)
  3. Dermatological toxicities, GI side effects (diarrhoea)
    EGFR+
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14
Q

Several management principles

A
  1. Treatments should not interfere with anti-tumour effects of EGFR inhibitors.
  2. Management should be achieved with minimal side effects.
  3. Ease of administration with rapid results are mandatory to ensure patient compliance.
  4. Therapies must be tailored to the type of clinical presentation.
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15
Q

Nomenclature of monoclonal antibodies

  • mab
  • rafenib
  • tinib
A
  • mab: monoclonal antibody
  • rafenib: Raf kinase inhibitor
  • tinib: tyrosine kinase inhibitor
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16
Q

Rituximab:

  1. MOA
  2. Toxicity
A
  1. Binds to CD20 receptor via macrophage or monocyte phagocytosis, complement activation, apoptosis.
  2. Toxicities
    - Infusion-related reactions (fever, chills, rigours, bronchospasm, hypotension)
    - nausea and vomiting
17
Q

How to manage infusion-related reactions:

A
  • close monitoring with time
  • pre-medicate with paracetamol and diphenhydramine
  • start infusion slow and increase with time
18
Q

Bevacizumab:

  1. drug class
  2. therapeutic use
  3. premed required?
  4. contraindications
  5. toxicities
A
  1. VEFGR
  2. colorectal cancer, lung cancer, kidney cancer
  3. no premedications required
  4. avoid in patients who are at high risk of bleeds or CNS metastasis; watch hypertension, proteinuria and risk of stroke.
  5. hemorrhage, thrombotic events, wound healing complications, GI perforations, proteinuria
19
Q

Trastuzumab:

  1. MOA
  2. Therapeutic use
  3. Toxicities
A
  1. HER2/Neu receptor antagonist
  2. Breast cancer, gastric cancer
  3. cardiotoxicity, hypersensitivity
20
Q

Ipilimumab:

  1. MOA
  2. Indications
  3. Side effects
A
  1. MOA: blocks the CTLA-4 inhibitory signal, allowing CTLs to destroy the cancer cells.
  2. Indicated for treatment of melanoma.
  3. Side effects are immunological-related: rash, diarrhoea, thyroid

Pharmacotherapeutics (28 decks)

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