Chemo from WM Flashcards
Definition: Partial response/remission?
Partial remission/response: decreased tumor volume by 50% or decreased max tumor diameter by >30%
Definition: Progressive disease?
Progressive disease: Increase in tumor volume > 25% or increase in tumor max diameter of > 20%; new lesion(s)
When do PFI/PFS begin counting?
PFI/PFS begins counting at the start of treatment.
Chemosensitivity of a cell depends on a number of factors including what?
Chemosensitivity depends on:
- Drug uptake into cell
- Interaction with a cellular target
- Generation of lethal damage to nb cell mols
- Repair of potentially lethal damage
- Cell’s response to generated damage
Name 4 chemotherapeutics actively transported into cells:
Actively transported into cells:
- Melphalan (two AA transporters)
- Cytosar (nucleoside transporter)
- Gemzar (nucleoside transporter)
- Methotrexate (reduced folate carrier)
Increased levels of which enzyme will increase 5-FU resistance?
Increased thymidylate synthetase decreases 5-FU sensitivity (increases resistance)
Definition: Therapeutic index
Therapeutic index: The ratio between toxic dose and therapeutic dose
Drug dosages are based on what?
Maximum tolerated dose (MTD), not efficacy
Definition: Radiosensitization
Radiosensitization: enhancement of cytotoxicity when irradiation and chemo are combined so therapeutic gain is achieved
Radiosensitization may involve: (1-3)
Radiosensitization may involve:
- enrichment of tumor cell pop in more sensitive cell cycle phase
- increased tumor oxygenation through cytoreduction or alterations in tumor vascularization
- selective killing of inherently radioresistant hypoxic cell fractions
Definition: partial remission/partial response
PR: decrease in tumor volume by 50% or more - OR - decrease in tumor max diameter of >30%
Definition: Progressive disease
PD: increase in tumor VOLUME >25% or increase in tumor max diameter of >20%; new lesions
Definition: DFI/DFS
DFI - amt of time that elapses w/o disease recurrence (or survival) or patient following therapy
Definition: PFI/PFS
PFI/PFS: Amt time elapsed w/o evidence of progressive tumor growth (PFI) or survival w/o progressive growth of tumor from treatment START (PFS)
Increased levels of this enzyme will decrease 5FU sensitivity
Increased levels of THYMIDYLATE SYMTHASE decrease 5FU sensitivity
Which enzyme metabolizes gemcitabine from a pro-drug?
deoxycytidine kinase transforms gemcitabine from a pro-drug to its di- and tri-phosphate forms
The ABCB1 mutation is expressed in which tumors?
ABCB1 expressed in…
Canine LSA, mammary, pulmonary carcinoma
Feline pulmonary carcinoma
Which ABC transporter/MDR mutations are expressed in canine mammary tumors?
Canine mammary tumors express:
ABCC1, ABCC2, ABCC10, ABCG2
What dose reduction is recommended for ACBC1 substrates in mut/mut patients?
Dose adjustments of 30-40% are recommended for ACBC1 substrates in mut/mut dogs
Vehicle induced mast cell degranulation is associated with which chemotherapeutics?
Vehicle-induced mast cell degranulation:
Paclitaxel and etoposide
Infusion hypersenstivity dt histamine release is associated with which chemotherapeutic?
Infusion hypersensitivity dt histamine release is associated with LSPAR
Definition: elimination half-life
Elimination half-life: time required for concentration of drug to reach half its original value
Cmax:
Cmax: the peak plasma concentratin of the drug after administration
Tmax:
Tmax: time to reach Cmax
Cmin:
Cmin: the lowest concentration of a drug before the next dose is administered
Steady state typically equals X-X times the half life
SS typically equals 4-5 times the half life
