Anticancer Drugs Flashcards
When are tumors most chemo-sensitive?
When they are small and have high growth fraction
What is growth fraction?
The fraction of tumor cells that are actively dividing
When does growth fraction increase and decrease?
Growth fraction decreases when tumor size becomes too large
What is adjuvant chemotherapy?
After Radiation or Surgery, chemotherapy is used to kill the rapid proliferating cells (more potential to respond to chemotherapy)
What is the name of the curve that shows the relationship between growth fraction and drug action? What does it show?
Gompertzian Growth curve; it show a high exponential growth fraction that, after it reaches the limit of clinical detection, plateaus to a lower growth fraction
What is log cell kill?
A first-order effect; chemotherapy kills a constant fraction of tumor cells and is proportional to the total number of cells present in the tumor; need to continue to do chemotherapy for an extended period of time even when no clinical signs of disease
What are phase non-specific drugs?
Drugs on cells in all phases of the cell cycle
What are the phase specific drugs?
Active only on cells that are in a specific phase of the cell cycle
What are S Phase-specific drugs? (3)
(1) Cytosine arabinoside
(2) Methotrexate
(3) Camptothecins (Topoisomerase I inhibitors)
What are M Phase-specific drugs?
(1) Vincristine
(2) Paclitaxel
What are Phase non-specific drugs?
(1) Alkylating drugs
(2) Cisplatin
What is the Goldie-Coldman hypothesis? What is the implication of this hypothesis?
The frequency of drug resistance is related to the intrinsic mutation rate of a given population of cells; Even the smallest detectable cancers are likely to contain drug-resistant forms; USE MULTIPLE DRUGS with different mechanism of action
What are the effects of resistance on the Therapeutic Index?
It takes a higher concentration of drug that is good for anti-cancer activity which means that there will be more toxicity associated with it
Cyclophosphamide: Mechanism of Action
Crosslinks with DNA to block replication and trigger cell death
Cyclophosphamide: Toxicities
(1) Myelosuppression
(2) Secondary Malignancies
(3) Bladder- hemorrhagic cystitis
T/F Cyclophosphamide is a prodrug.
TRUE
How can you eliminate hemorrhagic cystitis that is commonly caused with Cyclophosphamide?
(1) Hydration
(2) Masna
Cisplatin: Mechanism of Action
Crosslinks with DNA to block replication and trigger cell death
Cisplatin: Toxicities
(1) Peripheral neuropathy
2) Renal toxicity (major dose-limiting toxicity
What drugs do not cause myelosuppression? Why is this important?
(1) Cisplatin
(2) Vincristine
(3) Imatinib
- These drugs are easily combined with others because it will not have overlapping toxicity with other chemotherapy drugs
Topoisomerase I inhibitors (Topotecan): Mechanism of Action
Traps topo I-DNA complex resulting in formation of 1 DNA strand break (it inhibits the rejoining of DNA)
Topotecan: Toxicities
Myelosuppression
Topoisomerase II inhibitors (Doxorubicin and Etoposide): Mechanism of Action
Traps topo II-DNA complex resulting in double strand breaks in formation of DNA (inhibits rejoining the DNA)
T/F Topoisomerase II inhibitors are S-phase specific.
False. They are Phase independent!
