Lec 03 Cancer Chemotherapy

Question 1

Mechanism of action of Cytotoxic Chemotherapy

Answer 1

affect macromolecular synthesis and
function (DNA, RNA, Proteins)

Question 2

What type of drug is Cytosine?

Answer 2

ANTI-METABOLITE

Question 3

What type of drug is Paclitaxel?

Answer 3

MITOTIC INHIBITOR

Question 4

What type of drug is Doxorubicin?

Answer 4

ANTIBIOTIC

Question 5

What type of drug is Chlorambucil?

Answer 5

ALKYLATING AGENTS

Question 6

Why do we look at proliferating tissues more than normal

tissues affected by cytotoxic agents?

Answer 6

DNA becomes sensitive when the double helix is
unwound and open. Unwinding occurs only during the
time of cell proliferation. That is why proliferating cells
are more sensitive.

Question 7

Example of Cycle non-specific drugs

Answer 7

nitrosylureas and steroids

Question 8

Example of Cycle specific drugs

Answer 8

Alkylating agents and anti-tumor antibiotics

Question 9

How do you improve effectivity of a phase specific agent?

Answer 9

Increase time of exposure. This is to allow the rest of the cells in different phases to enter the sensitive phase.

Question 10

Antimetabolites work only on?

Answer 10

S phase

Question 11

Vinca alkaloids work only on?

Answer 11

M phase

Question 12

Anti-tumor antibiotics work on?

Answer 12

most of S phase including late phases of G1 and early phases of G2

Question 13

Alkylating agents work on?

Answer 13

all throughout the cell cycle

Question 14

Taxoids work on what phase?

Answer 14

Taxoids are spindle poisons so they only work on M phase.

Question 15

What is the usual mode of administration for cytotoxic drugs?

Answer 15

IV because they are poorly absorbed in the GIT and some drugs are irritants and contact to GI tissues may lead to lysis or giant ulcers that may not heal

Question 16

Name one cytotoxic drug that can be given orally

Answer 16

Cepacitabine - a prodrug converted to 5FU by enzymes in the liver

Question 17

What are the reservoir areas in males?

Answer 17

Brain and testes

Question 18

What is the result of poor nutrition in distribution?

Answer 18

Poor nutrition -> less protein -> more free drug

DANGEROUS

Question 19

What is the FRACTIONAL CELL KILL HYPOTHESIS?

Answer 19

States that each cycle of chemotherapy is capable of

destroying the same proportion of tumour cells.

Question 20

What is the minimum recovery time for chemotherapy?

Answer 20

3 weeks

Question 21

What are the assumptions of the Fractional cell kill hypothesis?

Answer 21

o All cells are rapidly dividing and are thus sensitive to
chemotherapeutic agents
o There is constant blood supply to be able to administer the drugs
o First order kinetics (meaning ALL cells are rapidly dividing)

Question 22

Tumours in which the logarithmic part of the curve is

shorter with a broader plateau phase will be (resistant/sensitive) to chemo

Answer 22

resistant like thyroid CA

Question 23

tumours with steep logarithmic curve will be (resistant/sensitive) to chemo

Answer 23

sensitive like lymphomas

Question 24

What are the two types of cell populations in the tumor?

Answer 24

Micrometastases – rapidly dividing and exhibiting logarithmic growth
Primary tumor – in the plateau phase of growth, some cells may be dividing, some may not

Question 25

What does the GOLDIE-COLDMAN HYPOTHESIS state?

Answer 25

within the tumor itself, there would be small population of tumor cells that are already naturally resistant to the effects of chemotherapy because of the labile genome that the cancer has

Question 26

How do you overcome resistance due to cell kinetics?

Answer 26

1. Debulking/Reduce tumor bulk with locoregional modalities(surgery, RT) 2. Use combinations that include drugs that can affect resting populations. 3. Schedule drugs to prevent phase escape or to synchronize cell populations and increase cell kill by continuous infusion instead of bolus.

Question 27

Most common cause of drug resistance in chemotherapy

Answer 27

MDR (multidrug resistance) or pleiotropic drug resistance

Question 28

What is the product of the MDR gene?

Answer 28

ATP dependent P glycoprotein that pumps the drug back outside. Hence, the drug does not reach the nucleus and cannot kill the cancer cell

Question 29

How do you overcome biochemical causes of resistance:

Answer 29

o Use combination chemotherapy o Use biologic response modifiers o Use a 2nd agent to rescue normal cells o Follow marrow-lethal doses of chemotherapy with autologous bone marrow transplant o Combine high dose chemotherapy with blood cell

Question 30

What is the definition of complete remission according to the RECIST Criteria?

Answer 30

disappearance of all target lesions

Question 31

What is the definition Progressive Disease (PD) according to the RECIST Criteria?

Answer 31

≥ 20% increase in SLD when compared to smallest SLD since treatment OR appearance of new lesions.

Question 32

When can you give chemotherapy to a pregnant woman?

Answer 32

late 3rd trimester

Question 33

What are the three phases of vomitting

Answer 33

1) acute (2hrs-1week) 2) delayed (1-2weeks after therapy) 3) psychogenic (triggered response)

Question 34

Most life threatening symptom of chemo

Answer 34

bone marrow aplasia

Question 35

symptom of anthracyclin use

Answer 35

Cardiotoxicity

Question 36

symptom of Bleomycin use

Answer 36

Pulmonary fibrosis

Question 37

What is the basic principle of ablative therapy?

Answer 37

the Hypothalamus-Pituitary-Organ axis should be interrupted

Question 38

When do you use Peripheral Androgen Inhibitors?

Answer 38

prostate cancer

Question 39

When do you use Selective estrogen receptor modulators ie tamoxifen?

Answer 39

Used in ER (+) breast cancer patients

Question 40

What is a side effect of tamoxifen?

Answer 40

Hot flushes, vaginal bleeding and discharge are associated with tamoxifen use. Vaginal bleeding is secondary to the induced proliferation of the endometrium and can actually lead to endometrial CA. So, if you use tamoxifen, it is advised that you also do an annual pap smear.

Question 41

What is passive immunotherapy?

Answer 41

Use of monoclonal antibodies for target cell-directed killing by antigen-antibody response

Question 42

What is adaptive immunotherapy?

Answer 42

acquisition of immunity in a naïve subject as the result of the administration of immunologically activated lymphoid cells.

Question 43

Imatinib is a selective tyrosine kinase inhibitor of?

Answer 43

KIT, Bcr-Abl, and PDGFR

Question 44

What is the mode of action of imatinib mesylate?

Answer 44

inhibit ATP phosphorylation in the BCR-ABL binding site, inhibiting the binding of tyrosine residues which further blocks the binding to the effector cell.

Question 45

GIST is dependent on what oncogene?

Answer 45

KIT oncogene

Question 46

Trastuzumab, a monoclonal antibody specific for what tumor?

Answer 46

breast tumor

Question 47

Cetuximab is specific for what tumor?

Answer 47

Lung, Colorectal, Head and Neck, GBM (glioblastoma?)

Question 48

Panitumumab is specific for what tumor?

Answer 48

colorectal

Question 49

Nimotuzumab is specific for what tumor?

Answer 49

Head and Neck, GBM

Question 50

What is the effect if mTOR is blocked?

Answer 50

If blocked: hold proliferation, starve the tumor, prevent metastasis, can make a tumor sensitive to hormonal therapy

Question 51

What is the function of the 26S proteosome

Answer 51

functions like the “anus” of the cell; takes all the proteins and degrades them so that they can be utilized again. Stopping the degradation will lead to an accumulation of toxic substances in the cell, ending in apoptosis.