Final: Anticancer PKPD

Question 1

Carcinomas are derived from _____

Answer 1

Epithelial Cells

Question 2

Sarcomas are derived from ______

Answer 2

Connective Tissue

Question 3

Lymphomas are derived from ____.

Answer 3

Lymphatic Tissue

Question 4

Leukemia are derived from _____

Answer 4

Blood forming elements.

Question 5

_____ is chemotherapy given before surgical procedure to remove a tumor.

Answer 5

Neoadjuvant

Question 6

______ is chemotherapy given to destroy left over cells which may be present after tumor is removed.

Answer 6

Adjuvant Therapy

Question 7

_____ therapy includes TKIs and antibody mediated therapy.

Answer 7

Targetted Thearpy

Question 8

Anticancer agents have a ____ therapeutic window with _____ interindividual variability.

Answer 8

Narrow
Wide (2-10 fold)

Question 9

_____ plots are used to measure duration-free survival plots for anti-cancer agents.

Answer 9

Kaplan Meier

Question 10

when paclitaxel is maintained above a Cp of _____ for _____ it has superior surivial according to one study covered in class.

Answer 10

0.1 for 15+ hours.

Question 11

Describe the interaction between 5-FU and Leucovorin.

Answer 11

Positive PD Interaction: Leucovorin enhances 5-FU by inhibiting thymidylate synthetase activity.

Question 12

Describe the interaction between platinum agents (cisplatin, carboplatin) and taxanes (paclitaxel and docetaxel).

Answer 12

When paclitaxel is followed by carboplatin, there is a decrease in the platinum adducts in the patients DNA. This leads to a reduction in off-target effects, and the ant-tumor activity of carboplatin.

Question 13

Which PK indices are used for anticancer agents commonly.

Answer 13

1. AUC
2. Css
3. Cmax
4. Exposure time above threshold.

Question 14

What is the problem with BSA Dose Optimization?

Answer 14

Simply because a patient has a higher BSA, does not mean they have larger organs as well.

Question 15

Carboplatin is priori dose adjusted based on _____ and _____.

Answer 15

Renal Function as it is 75% cleared by the kidney.

Toxicity (Thrombocytopenia) —> monitor AUC. –> Can predict change in platelet counts.

Question 16

Should we adjust doses simply because of age?

Answer 16

No, it is better to adjust based on individual physiology instead.

Question 17

For obese patients, what should we cap BSA at for calculations.

Answer 17

2.2 m^2

Question 18

Should we adjust complete priori dose adjustments based on pharmacogenomics for anticancer agents?

Answer 18

Yes

Question 19

How does 5-Fluorouracil under go priori based dose adjustment?

Answer 19

Pharmacogenomic Based

Patients with a deficiency of DPD should receive lower doses of this drug.

Question 20

How does 6-mercaptopurine under go priori based dose adjustment?

Answer 20

Based on the functional staus of thiopurine methyltransferase (TPMT) –> patients may clear this drug differently.

m/m = low CL
m/wt = mid CL
wt/wt= high CL (most common)

Question 21

How is population PK used for anti-cancer drugs?

Answer 21

Sets to identify covariates in PD. If co-variate is clinically significant then modify the dose.

Question 22

How does Dose-Limited Sampling Method work?

Answer 22

Sample at specific time points during the first course of therapy, then AUC can be adjusted using predictive models created by co-variate correlation to achieve target AUC.

Question 23

What is the limitation of LSM?

Answer 23

Needs to be applied to the same drug at the same dose, administration, and duration.

Question 24

How should methotrexate be monitored?

Answer 24

24-48 hours after start. Should be measured in 48 hour intervals.

Question 25

If Methotrexate levels are greater than 1 uM, then _____ blank should be used.

Answer 25

Leucovorin—> MTX levels are monitored every 48 hours afterwards and Leucovorin levels are adjusted until MTX is <1.