Anticancer PK/PD

Question 1

How are cancer cells generated?

Answer 1

Multiple gene mutations

Question 2

Solid tumors

Answer 2

Carcinomas and sarcomas

Question 3

Hematological tumors

Answer 3

Lymphomas, leukemias

Question 4

Treatment types

Answer 4

Surgery, radiation therapy, chemo, targeted therapy, immunotherapy, blood product donation and transfusion, stem cell transplant, vaccine, hyperthermia, photodynamic therapy, lasers

Question 5

Neoadjuvant therapy

Answer 5

Given before the surgical procedure to shrink cancer and procedure doesn’t have to be as extensive

Question 6

Adjuvant therapy

Answer 6

Destroy leftover cancer cells that may be present after the tumor is removed to prevent reoccurrence

Question 7

First-line

Answer 7

Treatment best to treat a certain cancer

Question 8

Second-line

Answer 8

Use if first-line doesn’t work, aka salvage therapy

Question 9

Palliative

Answer 9

Supportive care

Question 10

Cell cycle phase-specific agents

Answer 10

Appear to be most active during a particular phase but can be active in another phase

Question 11

Cell cycle phase-nonspecific agents

Answer 11

May have greater activity in one phase than another but not to the degree of cell cycle phase-specific agents

Question 12

PK of anticancer agents

Answer 12

Most have a narrow TI and wide inter-individual PK –> TDM

Question 13

Consequence of not being able to predict anticancer PK

Answer 13

Increased toxicity or sub-therapeutic dosing

Question 14

Effects/causes of decreased absorption of anticancer agents

Answer 14

N/V, prior surgery, radiotherapy, chemo affecting GI tract, DDI, decreased peristalsis

Question 15

Effects/causes of increased absorption of anticancer agents

Answer 15

DDI, increased peristalsis

Question 16

Effects/causes of decreased distribution of anticancer agents

Answer 16

Weight loss, decreased body fat

Question 17

Effects/causes of increased distribution of anticancer agents

Answer 17

Hypoalbuminemia, protein binding, peritoneal or pleural effusions

Question 18

Effects/causes of decreased elimination of anticancer agents

Answer 18

Decreased renal and/or hepatic dysfunction

Question 19

Effects/causes of increased elimination of anticancer agents

Answer 19

Induction of metabolism

Question 20

Indicator of efficacy

Answer 20

Toxicity

Question 21

Efficacy of MTX is associated with what?

Answer 21

Cmax

Question 22

PD drug interaction between 5-FU and leucovorin

Answer 22

Leucovorin enhances the effect of 5-FU by inhibiting thymidylate synthase

Question 23

PD DDI between cisplatin/carboplatin and paclitaxel/docetaxel

Answer 23

Administration of paclitaxel followed by carboplatin lead to a decrease in the formation of platinum adducts in patient DNA (aka decreasing the toxicity of carboplatin)

Question 24

Dose individualization: BSA-based

Answer 24

BSA has minimal clinical value in achieving consistent drug exposure but using BSA to dose adjust is still widely used

Question 25

A priori dose adjustment: renal function

Answer 25

Carboplatin is the only drug that's dosed based on GFR

Question 26

A priori dose adjustment: propensity for toxicity

Answer 26

Based on history of chemo and physiological status of patients, their propensity to manifest the known toxicity can be predicted and adjusted

Question 27

A priori dose adjustment: elderly and obesity

Answer 27

Aging can't be considered as an independent feature (can't be used to adjust doses alone) Limitation of calculated BSA at 2.2m^2 recommended for obese patients

Question 28

A priori dose adjustment: pharmacogenetics

Answer 28

5-FU is catabolized by DPD and patients who don't have much of this enzyme are at risk of life-threatening toxicity 6-MP is inactivated by TPMT and there's polymorphic populations that have different dose adjustments

Question 29

Dose adjustment based on population PK

Answer 29

Run a trial and get the PK, put it into some software and it builds a population model

Question 30

Limitation of LSM

Answer 30

Need to be applied and validated in treatments using the same anticancer agents, doses, administration schedules, and duration of infusion as the original study the LSM was established

Question 31

Rescue therapy for MTX toxicity

Answer 31

Leucovorin

Question 32

PK matrixes used to establish a correlation with efficacy/toxicity

Answer 32

AUC, Css, Cmax, time above a threshold concentration