Antineoplastic Agents Flashcards
Describe primary induction, neoadjuvant, and adjuvant therapies.
Primary induction - 1st line treatment
Neoadjuvant - Treatment given before primary induction to shrink the tumor
Adjuvant - Given after primary induction to prevent recurrence
What is the purpose and goals of primary induction chemotherapy?
Used for cancers in which no alternative treatment therapy exists.
Goals
- Palliate the patient
- Improve quality of life
- Prolong progression
What is growth fraction? Describe its relevance clinically and with respect to the progression of solid tumors.
Growth fraction - ratio of proliferating cells to those in G0
Tumors with a higher GF will respond with more success to chemotherapy
Solid tumors initially grow rapidly, but as they enlarge a higher portion of the interior mass enters G0 due to lack of nutrients and O2. You can increase GF through resection or radiation
Describe the effectivity of antineoplastic agents.
These drugs follow first-order kinetics, and always eliminate a fraction of cancer cells.
What is a pharmacologic sanctuary?
This is a region of the body where cancer cells are less susceptible. Could be the interior of solid tumors, the CNS, or testes.
Describe the characteristics of intermittent high-dose therapoy and continuous infusion.
Intermittent High-Dose Therapy - used for CCNS drugs. Allows normal tissues to recover and decreases the risk of infection
Continuous infusion - used for CCS drugs and those which are excreted/metabolized rapidly
What are the three advantages of combination therapy?
- Maximal cell killing
- Broader scope of effectivity
- Delay or prevent drug resistant tumors
What are the 5 principles of combination chemotherapy?
- Each drug has individual activity
- Operate by individual mechanisms
- Each drug has differing toxicities
- Scheduling allows shortest time of recovery for normal tissues
- Repeated exposure
Describe primary resistance, acquired resistance, and multi-drug resistance with respect to chemotherapy.
Primary resistance - due to genetic instability
Acquired Resistance - response to drug exposure, normally highly specific for a single drug
Multi-drug resistance - Due to expression of MDR1 gene –> surface transporter P-glycoprotein. This transporter confers resistance to anthracyclines, vinca alkaloids, dactinomycin, paclitaxel, and etoposide.
Note: P-gp can be blocked by calcium channel blockers such as verapamil
What are the common adverse effects of chemotherapy?
Nausea, vomiting, stomatitis, alopecia, myelosuppression, azoospermia, and growth retardation in children.
Myelosuppression results in anemia 10-14 days later, but recovery occurs by 28 days. Most regimens operate on a 28 day cycle.
How can side effects be minimized in chemotherapy, generally and with respect to myelosuppression?
Generally side effects can be avoided by change route of administration, direct perfusion, or removing the bone marrow. Myelosuppression can be specifically treated:
- Neutropenia can be treated with GM-CSF (sargramostim) or G-CSF (filgrastim/pelfilgrastin).
- Thrombocytopenia is treated with oprelvekin
- Anemia is treated with EPO or darbepoetin
Describe the CNS control of vomiting and how this adverse effect can be minimized?
There are 2 medullary control centrers for vomiting: The vomiting center and the chemoreceptor trigger zone. The CTZ is triggered in response to drugs and toxins. It signals the vomiting center to cause emesis.
Emesis can be reduced by administration of ondansetron, a serotonin antagonists.
Describe stomatitis, alopecia, and skeletal complications.
Stomatitis begins as erythema and edema, but progresses to ulceration.
Note: Proper oral hygiene can prevent secondary infection, but you cannot prevent stomatitis, unless modifying causative agent.
Alopecia occurs 2 weeks post-therapy, but can grow back once causative agents has been removed, although texture may be altered.
Skeletal complicaitons can be treated by bisphosphonates which inhibit osteoclast activity.
What are the types of alkylating agents and what is their general function?
Nitrogen mustards, methylhydrazines, alkyl sulfonates, nitrosureas, triazenes, and platinum compounds.
All of the drugs covalently bind to DNA.
Note: Platinum is not an alkylating agents, but does covalently bind to DNA
What is the MOA of alkylating agents?
These drugs covalently bind DNA causing inter- and intra-strand cross-linkages inhibiting the unwinding of DNA. Abnormal thymine pairing and depurination resulting in strand breaks can also occur.
These drugs are CCNS, but cells are most susceptible in late G1 and S phases
