238b intro to chemo Flashcards Preview

heme/onc > 238b intro to chemo > Flashcards

Flashcards in 238b intro to chemo Deck (16):
1

clinical trials - overview

Experimental study involving humans. Compares therapeutic benefits of 2 or more treatments,
or of treatment and placebo.

Study quality improves when study is randomized, controlled, and double-blinded (i.e., neither patient nor doctor knows whether the patient is in the treatment or control group). Triple-blind refers to the additional blinding of the researchers analyzing the data.

2

clinical trial - phase I
sample and purpose

small number of healthy volunteers

Is it safe? assesses safety, toxicity, pharmcokinetics

3

clinical trial - phase II
sample and purpose

small number of patients with disease of interest

does it work? Assesses treatment efficacy, optimal dosing, adverse effects

4

clinical trial - phase III
sample and purpose

Large # of patients randomly assigned to either treatment under investigation OR placebo/best available

Is it as good or better? Compare new treatment to SOC

5

clinical trial - phase IV
sample and purpose

postmarketing surveillance trial of patients after approval

Can it stay? long term adverse effects

6

chemo regiments - how many drugs? what should be considered?

multi-agent - combo therapy to overcome inherent drug resistance + prevent acquired resistance

drugs shouldn't overlap in mechanism or toxicity

7

adjuvant chemotherapy

Follows surgery - some chemo is more effective without overt disease (ie better at micro tumors than macro)

smaller micro deposits has larger fraction of proliferating cells (better vascular supply) + lower probability that resistant cells present based on number of cells

8

neoadjuvant chemo

before surgery

shinks tumor --> resection easier --> followed by adjuvant chemo

favorable response provides justification to continue the same chemo post surgery

9

how big of chemo dose should be used? why?

max tolerable dose

steep-dose response curve (a small increase in dose results in large increase of killing of tumor)

10

Therapeutic index

measurement of drug safety

TD50/ED50 = median toxic dose/median effective dose

"TITE" TI=TD/ED

safe drugs = higher TI value

11

pharmacokinetics - overview?

what the body does to the durg

ADME (absorption, distribution, metabolism, excretion)

determines route of drug admin

12

pharmacodynamics - overview?

what does drug due to body

relationship between concentration and efficacy/toxicity

determines if effective does can be given

13

pharmacogenetics - overview?

how genome affects the drug --> genetic variation changes enzymes differences

14

conventional chemo vs targeted

cytotoxic - non selective that affect dividing cells (normal and cancer) -- often interfere with DNA/RNA synthesis or function

molecularly targeted - more selective, inhibit protein kinase activity often -- sometimes target cancer cell surface proteins

15

Alkylating agents/cisplatin
-mechanism
-classes
-toxicities

covalent binding of alkyl groups --> cross-link DNA --> apoptosis

nitrogen mustards(cyclophosphamide/ifosfamide)
nitrosoureas
platinum compounds (non-classical alkylating)

myelosuppression
gonadal atrophy/infertility
secondary leukemia

16

antimetbolites
-mechanism
-classes/drugs
-toxicities

inhibit synthesis of nucleic acids via incorporation into DNA/RNA b/c structural analogs --> block S phase

folate analogs: methotrexate

purine analogs: azathioprine, 6-metacptopurine (6-MP), 6-thioguanine (6-TG)

pyrimidine analogs: cytarabine, 5-flurouracil (5-FU)