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

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.


clinical trial - phase I
sample and purpose

small number of healthy volunteers

Is it safe? assesses safety, toxicity, pharmcokinetics


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


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


clinical trial - phase IV
sample and purpose

postmarketing surveillance trial of patients after approval

Can it stay? long term adverse effects


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


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


neoadjuvant chemo

before surgery

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

favorable response provides justification to continue the same chemo post surgery


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)


Therapeutic index

measurement of drug safety

TD50/ED50 = median toxic dose/median effective dose


safe drugs = higher TI value


pharmacokinetics - overview?

what the body does to the durg

ADME (absorption, distribution, metabolism, excretion)

determines route of drug admin


pharmacodynamics - overview?

what does drug due to body

relationship between concentration and efficacy/toxicity

determines if effective does can be given


pharmacogenetics - overview?

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


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


Alkylating agents/cisplatin

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

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

gonadal atrophy/infertility
secondary leukemia



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)