Flashcards in Antineoplastics VI: Treatment Strategies Deck (18)
How are antineoplastics almost always given?
Correct selection of drugs in a regimen can result in . . .
. . .decreased development of resistance, synergistic effects and decreased toxic effects.
What are other common chemotherapeutic strategies (other than combination therapy)?
-Pulse and rescue therapy
What is pulse therapy?
-Intermittent treatment with very high doses of a drug, followed by drug-free periods
-Allow hematologic and immunologic recovery between treatment cycles
Example: Methotrexate for the treatment of choriocarcinoma
What is rescue therapy?
-Following administration of toxic doses of a chemotherapeutic agent, normal cells can be rescued by giving "antidotes" that only they can use
Example: Leucovorin following high dose Methotrexate treatment
What are the principles of drug selection?
-Active when used alone
-Different MOA (including diff. mechanisms for the development of resistance) and/or different chemical classes
-CCNS vs. CCS or active in different stages of cell cycle
---Enables use of more specific strategies (esp. recruitment and synchrony)
What is the result of appropriate drug selection?
-Synergistic effects (effect greater than the sum of the actions of the individual drugs) --> lower doses --> decreased toxicity
--e.g. CYTARABINE + 6-THIOGUANINE
-Decreased development of resistance
-Broader cell kill in cancers that consist of a heterogenous tumor cell population
What is recruitment?
-Use a CCNS drug to achieve a significant log kill
-This will cause cancer cells in G0 to be recruited back into the cell cycle
-Administer a CCS drug to kill diving cells
---CMF in breast cancer
---Daunorubicin + Cytarabine in AML
What is synchrony?
-Using CCS drugs to synchronize cells into simultaneous cell division , so that they are more sensitive to other drugs or radiation
-Timing the delivery of drugs so that the action of one drug doesn't interfere with the actions of another
---Hydroxyurea followed by radiation
---Vinc alkaloids (m Phase) followed by another CCS drug like Etoposide (S phase)
---Methotrexate followed by L-asparaginase for the treatment of acute lymphocytic leukemia
What is the ABVD regimen?
A- Adriamycin = Doxorubicin
What is the MOA, resistance and unique toxicity of Adriamycin = Doxorubicin?
-MOA: CCNS Intercalating
-Resistance: P-glycoprotein, Changes in target, Increased inactivation
-Toxicity: Cardiotoxicity, Myelosuppression
What is the MOA, resistance and unique toxicity of Bleomycin?
-MOA: CCS (G2), Strand breaks (unique)
-Resistance: Increased DNA repair, Increased inactivation
-Toxicity: Skin and lungs (not myelosuppression)
What is the MOA, resistance and unique toxicity of Vinblastine?
-MOA: CCS (M) - disrupts microtubules
-Resistance: P-glycoprotein, Changes in target
-Toxicity: Neurotoxicity, Myelosuppression
What is the MOA, resistance and unique toxicity of Dacarbazine?
-MOA: CCNS, Alkylating agent
-Resistance: Nucleophile production, Increased DNA repair
What is the MOPP regimen and what is it used for?
Mechlorehamine, Oncovin=vincristine, Prednisone, Procarbazine
What is the COP (+/- D = COPD) and what is it used for?
What is PVB and what is it used for?
Platin (carbo- or cis-)