Lec 2/3 Heme/Onc
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What factors affect response to chemotherapy?
- 1. tumor heterogeneity
- 2. tumore size & site (penetration & vascularization)
- 3. drug dose & schedule/dose intensity (intensity = major determinant of response
- 4. drug resistance
- 5. patient characteristics (functional status, organ function, age, size, etc.)
- 6. pharmacogenomics (genetic variants may impact how well body metabolizes specific drugs)
What is the rationale for combination chemotherapy? Advantages? Disadvantages?
- Rationale: tumor cell heterogeneity, acquired resistance to single agents, increased response rate (synergy)
- Advantages: multiple mechanisms of action
- Disadvantages: complicated administration schedules, toxicities, cost
What is the rational for 1-3 week interval between chemotherapy courses?
- 1. tumor response: lock-step cell cycle for cells to become more homogeneous
- 2. allows for recovery from adverse effects
What are drug-resistance mechanisms for chemotherapy?
- 1. inability to distribute to the tumor: CNS tumors
- 2. diminished tumor cell uptake or influx (mdr gene, pgp)
- 3. inactivation within tumor cells
- 4. enhanced tumor cell efflux (pgp-mediated MDR)
- 5. ability to repair DNA damage (from alkylators, bleomcin)
- 6. altered target enzyme activity or amount
What dosage forms and routes of administration are available for chemotherapy?
- 1. oral
- 2. IV
- 3. depot forms from intramuscular injection
- 4. liposomal compounds
- 5. direct application to tumor site (intrathecal = brain)
- 6. bladder instillation
- 7. intrahepatic (chemoembolization)
When are cytotoxic effects exerted in cell cycle non-specific chemotherapy agents?
throughout the cell cycle
When are cytotoxic effects exerted in cell cycle specific chemotherapy agents?
specific cell phase
Are cell cycle non-specific chemotherapy angents efficacious against cells in the resting phase?
Are cell cycle specific chemotherapy angents efficacious against cells in the resting phase?
only is specific phase of cycle
What kind of general drug dosing does cell cycle non-specific chemotherapy agents have?
- DOSE DEPENDENT
- degree of kill proportional to dose
What kind of general drug dosing does cell cycle specific chemotherapy agents have?
- SCHEDULE DEPENDENT
- best kill when dose is divided and given in repeated fractions
What is complete response?
disappearance of all cancer without evidence of new disease for at least 1 month
What is a partial response?
a decrease in the size of a tumor (~ < 30%), or in the extent of cancer in the body, in response to treatment
What is progressive disease?
cancer that is growing, spreading, or geting worse (~ > 20%)
What is stable disease?
no growth or disappearance by above criteria
What is progression-free survival?
a measure used in clinical trials to show length of time that cancer is not getting worse while participant is on a treatment
What is clinical benefit?
- a measure in clinical trials to show that treatment may have benefit
- examples: improved quality of life, less use of analgesics, etc.
What is the response criteria for hematologic tumors?
- 1. elimination of abnormal cells
- 2. cytogenic response
- 3. molecular response
What is the process for reviewing a chemotherapy order?
- P= person (right pt, age, performace status, cancer type, stage, goal)
- R= regimen (reference, which cycle is pt on in regimen, right dose, drug & schedule)
- O= organ function (renal/hepato adjustments, ANC)
- N= numbers (ht/wt, BSA)
- T= toxicities (drug toxicities & preventable measures; supportive meds: fluids, antiemetics, premedication)
- O= order entry (double check labels printed clearly/correctly; clear durg & fluid volume)
How do you calculate CrCl?
- (140-age) x (weight in kg) x 0.85 (if female) = ml/min
- (72) x (SCr)
How is BSA calculated?
- m2 = square root of: height (cm) x weight (kg) / 3600
- m2 = square root of: height (in) x weight (lb) / 3131
How is ANC calculated?
WBC x (segments + bands)
- ex: seg = 30; bands = 6; WBC = 8000
- 8000 x (30 + 6) = 2880/mm3
- normal range: 1.5 - 8.0 (1500-8000/mm3)
How is carboplatin dose calculated?
dose (mg) = target AUC x (CrCl + 25)
target AUC indicated by MD --> usually 4-8 mg/ml/min
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