Describe the normal cell cycle
Describe barriers to treatment with chemotherapy
Toxicity to normal cells-drugs lack selective toxicity
- Need for 100% kill for cure
- First Order Kinetics
- Lack of Immune Involvement
- Unknown Cure Interval
Lack of early detection: Usually at least 1 million cells needed for symptoms, up to 1 billion cells for mass to be detected. Consequences: metastasis, decrease in drug responsiveness, worsening health of patient
The larger the tumor, the less responsive it is to cytotoxic medications-lower growth fraction, less blood supply to core
- debulking (Surgically taking out the visable tumor)
Drug Resistance: Reduced drug uptake, increased drug efflux, reduced drug activation, increased repair of drug induced DNA damage.
Heterogeneous tumor cells
Location: Especially CNS, large solid tumors
Describe methods to overcome chemotherapy barriers
Intermittent chemo is a great way, cause it allows normal cells some time to recover
Combination of cytotoxic medications
- Suppresses drug resistance-less likely to have multiple mutations
- Increased rate of tumor cells kill
- Decrease in injury to normal cells-use drugs with different toxicities
Understand common toxicities associated with chemotherapy
Bone Marrow related suppression!
Neutropenia - Nadir
N & V
Hair loss (Alopecia)
Hyperuricemia (That’s why we give allopurinol)
Toxicity to heart lung and kidneys is unique.
Differentiate between cell-cycle phase specific and non-specific cytotoxic drugs
Cell-Cycle Phase Specificity
- Cell-cycle phase nonspecific: affects cells during any phase of cycle.
- Cell-cycle phase specific: because of mechanism of action, about ½ of cytotoxic drugs work during specific phase.
Discuss the utility of hormone modifiers
Least toxic of anticancer medications
Work at specific hormone receptors so highly selective
Most are used for breast, endometrial and prostate cancers
Glucocorticoids also used in lymphomas and leukemias
Glucocorticoids: Directly toxic to lymphoid tissues.
Antiestrogens: Blocks estrogen stimulation of cancer cells.
Aromatase Inhibitors: Postmenopausal women only-blocks production of estrogen from androgen precursors but not ovaries
GNRH Antagonists-for prostate CA, endometriosis. “Chemical castration”.
Discuss action and side effects of immunostimulants
Normally produced in response to viral infections and other stimuli, active against many solid tumors and hematologic malignancies
Enhance host immune response and also has direct antiproliferative effect on cancer cells
SE: Flu-like symptoms, prolonged high dose can cause bone marrow suppression.
Describe the mechanism of action of imatanib (Gleevac)
Inhibits Philadelphia chromosome
Oral therapy for CML
Indefinite therapy, very expensive
Understand long term effects of chemotherapy and radiation
Deficits of language, memory, and attention
Atrophy of gray matter
Loss of hearing and vision
Cardiomyopathy due to medications as well as radiation therapy
Xerostomia (facial radiation)
Fibrosis secondary to medication
Pneumonitis due to radiation
Understand tumor lysis syndrome. When are patients most at risk? What systems are most affected?
Patients most at risk 1-3 days after chemotherapy
Seen in rapidly growing cancers after administration of chemotherapy
Kidneys and Heart are most affected I’m not 100% about this
- Heart for sure, tumor lysis syndrome causes lysis of cells which releases intercellular potassium causing cardiac dysrhythmias.