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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)
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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
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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
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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
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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)
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When are cytotoxic effects exerted in cell cycle non-specific chemotherapy agents?
throughout the cell cycle
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When are cytotoxic effects exerted in cell cycle specific chemotherapy agents?
specific cell phase
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Are cell cycle non-specific chemotherapy angents efficacious against cells in the resting phase?
Yes
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Are cell cycle specific chemotherapy angents efficacious against cells in the resting phase?
only is specific phase of cycle
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What kind of general drug dosing does cell cycle non-specific chemotherapy agents have?
- DOSE DEPENDENT
- degree of kill proportional to dose
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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
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What is complete response?
disappearance of all cancer without evidence of new disease for at least 1 month
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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
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What is progressive disease?
cancer that is growing, spreading, or geting worse (~ > 20%)
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What is stable disease?
no growth or disappearance by above criteria
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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
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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.
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What is the response criteria for hematologic tumors?
- 1. elimination of abnormal cells
- 2. cytogenic response
- 3. molecular response
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What is the process for reviewing a chemotherapy order?
- PRONTO
- 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)
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How do you calculate CrCl?
Cockcroft-Gault:
- (140-age) x (weight in kg) x 0.85 (if female) = ml/min
- (72) x (SCr)
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How is BSA calculated?
- m2 = square root of: height (cm) x weight (kg) / 3600
- m2 = square root of: height (in) x weight (lb) / 3131
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How is ANC calculated?
WBC x (segments + bands)
- ex: seg = 30; bands = 6; WBC = 8000
- 8000 x (30 + 6) = 2880/mm3
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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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