Antineoplastics VI: Treatment Strategies Flashcards
How are antineoplastics almost always given?
In combination
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
- Recruitment
- Synchrony
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
- Different toxicities
- –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
Examples:
—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
Examples:
—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
B- Bleomycin
V- Vinblastine
D- Dacarbazine
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
- Toxicity: Myelosuppression
What is the MOPP regimen and what is it used for?
Mechlorehamine, Oncovin=vincristine, Prednisone, Procarbazine
-Hodgkin Lymphoma
