238b intro to chemo

Question 1

clinical trials - overview

Answer 1

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.

Question 2

clinical trial - phase I

sample and purpose

Answer 2

small number of healthy volunteers

Is it safe? assesses safety, toxicity, pharmcokinetics

Question 3

clinical trial - phase II

sample and purpose

Answer 3

small number of patients with disease of interest

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

Question 4

clinical trial - phase III

sample and purpose

Answer 4

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

Question 5

clinical trial - phase IV

sample and purpose

Answer 5

postmarketing surveillance trial of patients after approval

Can it stay? long term adverse effects

Question 6

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

Answer 6

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

drugs shouldn’t overlap in mechanism or toxicity

Question 7

adjuvant chemotherapy

Answer 7

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

Question 8

neoadjuvant chemo

Answer 8

before surgery

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

favorable response provides justification to continue the same chemo post surgery

Question 9

how big of chemo dose should be used? why?

Answer 9

max tolerable dose

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

Question 10

Therapeutic index

Answer 10

measurement of drug safety

TD50/ED50 = median toxic dose/median effective dose

“TITE” TI=TD/ED

safe drugs = higher TI value

Question 11

pharmacokinetics - overview?

Answer 11

what the body does to the durg

ADME (absorption, distribution, metabolism, excretion)

determines route of drug admin

Question 12

pharmacodynamics - overview?

Answer 12

what does drug due to body

relationship between concentration and efficacy/toxicity

determines if effective does can be given

Question 13

pharmacogenetics - overview?

Answer 13

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

Question 14

conventional chemo vs targeted

Answer 14

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

Question 15

Alkylating agents/cisplatin

• mechanism
• classes
• toxicities

Answer 15

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

Question 16

antimetbolites

• mechanism
• classes/drugs
• toxicities

Answer 16

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)