Anti-Cancer Drugs

Question 1

What is the difference between Neo-adjuvant and adjuvant therapy?

Answer 1

Neo-adjuvant: Pre-operative to downstage tumor before surgery or radiotherapy

Adjuvant: Post operative

Question 2

Intraperitoneal therapy are used for _____ cancer

Answer 2

Ovarian

Question 3

Intravesical therapy are used for ____ cancer

Answer 3

Bladder

Question 4

Name 2 Alkylating agents

Answer 4

• Cyclophosphamide
• Chlorambucil

Question 5

Are alkylating agents cell cycle phase specific or non-specific?

Answer 5

Non-specific

Question 6

Cell cycle-specific drugs kill cells only during ___ phase or ___ phase

Answer 6

S and M phase

Question 7

Are platinum analougues cell cycle phase specific or non-specific?

Answer 7

Non-specific

Question 8

LIst 3 examples of platinum analouges

Answer 8

• Cisplatin
• Carboplatin
• Oxaliplatin

Question 9

Are anti-matabolites cell cycle phase specific or non-specific?

Answer 9

S phase specific

Question 10

Methotrexate is commonly used for ____ cancer and ____

Answer 10

Breast cancer and lymphoma

Question 11

List 3 examples of Anthracyclines (cytotoxic antibodies)

Answer 11

• Doxorubicin
• Daunorubicin
• Idarubicin
• Epirubicin

Question 12

Are Anthracyclines cell cycle phase specific or non-specific?

Answer 12

Non-specific

Question 13

LIst 3 examples of Microtubule inhibitors

Answer 13

- Paclitaxel
- Docetaxel
- Cabazitaxel

Question 14

Are microtubules inhibitor cell cycle phase specific or non-specific?

Answer 14

M phase specific

Question 15

Which 2 group of medications are cell cycle phase specific?

Answer 15

• Anti-metabolites (e.g Methotrexate, 5-fluorouracil)
• Microtubule inhibitors (e.g. Paclitaxel)

Question 16

What is one tyrosine kinase inhibitor?

Answer 16

Imatinib
Used in treatment against Philadelphia Chromosome Positive Chronic Myelogenous Leukemia

Prevents the binding of ATP, without ATP the energy source, BCR-ABL will not be able to function and signal downstream

Question 17

Name one neutralizing antibody

Answer 17

Bevacizumab (Avastin)

Question 18

Exaplain the MOA of Bevacizumab

Answer 18

Anti-VEGF therapeutic antibodies bind to and neutralise VEGF receptors, which are key receptors on endothelial cells. Normally. VEGF-A binds to VEGFR-2, causing activation of downstream signalling pathways that drive angiogenesis. The anti-VEGF antibodies bind to VEGF-A and inhibit VEGF extracellularly, thus blocking angiogenesis.

Question 19

Name a antibody-drug conjugate (ADC)

Answer 19

Brentuximab

Question 20

Briefly explain Molecular-targeted radiotherapy

Answer 20

Similar to external beam therapy:
- cancer cell destruction is achieved by means of radiation-induced DNA damage

Similar to chemotherapy
- A systemic treatment that uses a molecule, in this case bearing a radiolabel to deliver cytotoxic substance to disease state

Has a bystander or crossfire effect
- potential destruction of adjacent cells, important as tumors are heterogenous tissues

For primary and metastatic tumors
- including malignant cell populations undetectable by diagnostic imaging

Question 21

Briefly explain CAR T-cell Immunotherapy

Answer 21

1. Extract T cells - collect T Cells from patient
2. Reprogramming T cells - viral vector inserts CAR gene into T cells
3. Manufacturing CAR T-cells - Car T cells are proliferated in vitro to a specific clinically relevant quantity and quality
4. Patient pre conditioning- patient are treated with chemo to lower white blood cell count to more readily accept T cells
5. Treatment - Patient is given CAR T-cells

Question 22

Name one immune checkpoint inhibitor

Answer 22

Ipilimumab (Human monoclonal Ab)

It blocks CTLA-4 and acts as immunotherapy by activating T cells response and immune surveilance

Question 23

List 2 examples of treatment options available for cancer

Answer 23

• Surgery
• Radiotherapy
• Chemotherapy
• Molecular targeted therapy

Question 24

List 3 advantage of chemotherapy combinations

Answer 24

1. Maximal cell kill below toxicity threshold for each drug
2. Broader cell killing across heterogenous tumor cell populations
3. Prevent or slow development of drug resistance

Principles:
1. Efficacy: only drugs with single agent efficacy for a particular tumor should be combined
2. Toxicity: non-overlapping toxicity as minimizes lethal effect and allows maximization of dose intensity
3. Optimum Scheduling: should be used at optimal dose and schedule, shortest time for recovery
4. Mechanism of interaction: clear understanding of drug interactions to allow maximum effect
5. Avoidance of dose changes: reduction of dose of one drug to add other drugs to combination may lower efficacy

Question 25

3 common chemotherapy regimens

Answer 25

Breast Cancer (AC-T):
Adriamycin, Cyclophosphamide, Paclitaxel

Hodgkin’s lymphoma (AMVD): Doxorubicin, Bleomycin, Vinblastine, Dacarbazine

Non-hodgkin’s lymphoma (CHOP): Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone

Question 26

What are some common chemotherapy side effects?

Answer 26

• Nausea and Vomitting
• Myelosuppression
• Alopecia

Late organ toxicity:
- Cardiotoxicity
- Pulmonary toxicity
- Nephrotoxicity
- Neurotoxicity
- Secondary Malignancies

Question 27

Why are chemotherapeutic drugs given in cycles?

Answer 27

Log kill hypothesis
A one log drug kills 90% of the cells, a two log drug kills 99% and a three log drug kills 99.9%