Oncology Flashcards
What types of cancers cause the most deaths yearly?
Lung, stomach, liver, colon, and breast cancer cause the most deaths each year
What are the highest risk factors associated with developing cancer?
Tobacco use is the most important risk factor (22% of global cancer deaths and 71% of lung cancer deaths)
High body mass index
Low fruit and vegetable intake- due to antioxidants
Lack of physical activity
Alcohol use
What are the characteristics that cancer shares?
Uncontrolled proliferation
Local invasiveness
Tendency to metastasis
Changes in some aspect of original cell morphology
What is cancer cure defined as?
The disappearance of any evidence of tumor for 5 years and a high actuarial probability of a normal life span
What are the three principle methods that attempt to cure or palliate cancer?
Surgery
Radiotherapy
Chemotherapy
What does chemotherapy drugs do?
Inhibit rate of growth
Kill cancerous cells
Have minimal effects on non-neoplastic host cells
What do anticancer agents target?
Malignant cells in preference to non-malignant cells-through the molecular differences between them
What are the chemotherapeutic techniques?
Cytotoxic therapy
Endocrine therapy
Immunotherapy
Cytotoxic therapy- MOA
-Affect DNA synthesis
-Classified according to their site of action on the process of DNA synthesis within the cancer cell.
-Most active against cycling/proliferating cells
Normal – hair, skin, stomach lining, blood cells
Malignant- goal is to target these.
-Phase specific killing–drugs that are effective at killing cycling cells during specific parts of the cell cycle.
-Cycle specific–cytotoxic throughout the cell cycle
Cytotoxic drugs have a low selectivity for what non-cancer cells that undergo rapid division?
GI
Bone Marrow
Reproductive
Immune systems
Why can selectivity occur w/some cancers for cytotoxic drugs?
- Malignant tumors have a higher proportion of cells undergoing proliferation than in normal proliferating tissues.
- Normal cells recover from chemotherapeutic inhibition faster than some cancer cells.
- Synchronized cell cycling may leave discrete period of vulnerability to cytotoxic drugs
How do cytotoxic drugs work?
Cytotoxic drugs kill a constant fraction, not a constant number of cells; lays down the foundation for chemotherapeutic dosing schedules.
Cytotoxic drugs- resistance
Genetic resistance
Inherited to the cancer cell line- drugs don’t work on it at all
Acquired during the course of chemotherapy as a result of selection by the agent.
If you don’t give enough or stick to the right therapy then the patient can develop immunity.
Cytotoxic drugs- MOA of resistance
Abnormal transport
Decreased cellular retention- cell doesn’t retain the drug that you are giving
Increased cellular inactivation (binding/metabolism)- binds or metabolizes the drug away
Altered target protein
Enhanced repair of DNA- respond more like normal cells to recover faster.
Altered processing
When where can resistance for cancer chemotherapy occur if cancer is in pharmacologic sanctuaries?
Blood-brain barrier- cancers in here are hardter to treat because of the bateir and you need the meds to get past the BBB so end up doing surgery.
Large solid tumor w/low blood supply and diffusion
What are the cytotoxic agents?
- Alkylating agents
- Antimetabolites
- Cytotoxic antibiotics
- Mitotic (Microtubule) inhibitors
- Miscellaneous agents
Where are alkylating agents capable of introducting alkyl groups into?
Capable of introducing alkyl groups into nucleophilic sites on other molecules through the formation of covalent bonds.
What are the nucleophilic targets of alkylating agents?
Nucleophilic Targets—present in macromolecules and low molecular weight compounds w/in cells:
Sulfhydryl Hydroxyl
Amino Carboxyl
Phosphate Imidazole
What are the macromolecular sites of alkylation damamage of alkylating agents?
DNA
RNA
Various enzymes
DNA synthesis inhibition requires lower drug concentrations than inhibition of RNA and protein synthesis.
Nitrogen mustards- Mechlorethamine (Mustargen)- pharmacokinetics
Plasma half-life after IV injection ~ 10 minutes (really fast)
Little or no intact drug excreted in urine (body destroys really quickly)
Nitrogen mustards- Mechlorethamine (Mustargen)- Indications
Major—Hodgkin’s disease
Treated w/MOPP (meclorethamine, (Oncovin) vincristine, procarbazine, prednisone)
Less reactive nitrogen mustards now preferred for treatment of non-Hodgkins lymphomas, leukemias and various solid tumors.
Nitrogen mustards- Mechlorethamine (Mustargen)- dose-limiting toxicities
MYELOSUPPRESSION
Maximal leukopenia and thrombocytopenia occurs w/in 10-14 days post administration—recovery complete 21-28 days.
Lymphopenia and immunosuppression may lead to activation of latent herpes zoster.
Nitrogen mustards- Mechlorethamine (Mustargen)- ADRs
Will affect rapidly proliferating normal tissues and cause: Alopecia, Diarrhea, Oral ulceration.
N/V/ 1-2 hours after inj can last up to 24 hours
Causes blistering—avoid extravasations and spillage
Reproductive toxicities
Amenorrhea
Inhibitor of oogenesis and spermatogenesis
½ premenopausal women and almost all men treated for 6 mo. w/MOPP become sterile.
Cyclophosphamide (Cytoxin)- MOA
Alkylating Agents
Must be activated by P450 enzyme system
Cytotoxic metabolites include (products that are seen when cyclophosphamide is metabolized but if you give a P450 inhibitor then you wont get these)
Phosphoramide mustard
acrolein