EXAM 3 - Oncology - Just the Stars - GANNAWAY Flashcards
Cell-cycle specific
Chemotherapeutic agents that are only effective on high growth fraction cancer cells.
Cell-cycle nonspecific
Chemotherapeutic agents that are effective on both low growth fraction and high growth fraction cancer cells.
Growth Fraction
The fraction of cancer cells that are actively replicating (cycling) in the cell cycle.
When is chemotherapy the only treatment option?
cancer that is disseminated and not amenable to surgery and/or radiation
Adjuvant Chemotherapy
Supplemental chemotherapy that is given following surgery and/or radiation to eliminate undetected micrometastases.
Neoadjuvant Chemotherapy
Chemotherapy that is given prior to surgery and/or radiation to decrease the size of a solid tumor.
Maintenance Chemotherapy
continued after initial ﾓcureﾔ to prevent recurrence or, in advanced cancer, to keep it from growing and spreading.
Myelosuppressant
A chemotherapeutic agent that affects bone marrow and inhibits the formation of mature blood cells, particularly white blood cells, red blood cells and platelets.
Vesicant
A chemotherapeutic agent that causes redness and blistering on the skin. If such an agent is extravasated during intravenous administration, there will be severe damage to the tissue in the extravasation area.
Growth Fraction
The fraction of tumor cells that are in the replicative cycle (i.e., growth fraction)»_space; influences their susceptibility to most chemotherapeutic agents.
High growth fraction vs. Low growth fraction
Cells that are rapidly dividing have a high growth fraction and are typically more susceptible to chemo than cells with a low growth fraction.
Cell-cycle specific
Chemotherapeutic agents that are only effective against high growth fraction cells
Cell-cycle nonspecific
effective against both high and low growth fraction cancers.
Significance of 1-g Tumor Mass
A total of 10^9 cells is the smallest tumor burden that is physically detectable; these 1 billion cells represent a tumor weighing about 1 g or about the size of a small grape; clinical symptoms usually first appear at this stage
Palliative Chemotherapy
Initial remissions are transient, with symptoms recurring between txs. Survival is extended, but the patient eventually dies of the disease.
Curative Chemotherapy (for disseminated cancers, such as leukemia)
Combination-drug chemo reduces the chance of drug resistance. Each drug chosen to have different cellular site of action or different cell-cycle specificity. Each drug chosen to have different organ toxicity.
Curative Chemotherapy (for solid cancers, such as testicular carcinoma)
Tumor burden is initially reduced by surgery and/or radiation; tx of occult micrometastases is continued after clinical signs of cancer have disappeared.
Susceptibility of cells to chemo
rapidly dividing have a high growth fraction and are typically more susceptible to chemo than cells with a low growth fraction. Also applies to normal cells that rapidly proliferate.
Normal cells most affected by chemo
1) Buccal mucosa
2) Upper GI tract (mouth, throat and esophagus)
3) Hair follicles
4) Bone marrow
5) Small intestine
6) Treatment-induced cancermo agents cause cancer years later.
7) Extravasation
Effects of chemo on buccal mucosa
stomatitis.
Effects of chemo on upper GI
mucositis.
Effects of chemo on hair follicles
hair loss or alopecia.
Effects of chemo on bone marrow
myelosuppression that can affect white blood cells (neutropenia), red blood cells (anemia) and platelets (thrombocytopenia).
Effects of chemo on small intestine
Interacts with the chemoreceptor trigger zone in the brain to cause nausea and vomiting.
Treatment-induced cancer
mutagenic effects of some chemo agents can cause cancer years later.
Extravasation
parenteral vesicants can cause significant soft tissue damage.
What are chemotherapy adjuncts (general)?
Treatments that help alleviate chemotherapy-induced side effects.
Why are chemotherapy adjuncts used?
1) THEY HELP ALLEVIATE CHEMOTHERAPY-INDUCED SIDE EFFECTS.
2) They help make the action of chemotherapy drugs
more effective.
3) They help alleviate symptoms of the cancer.
Chemotherapy adjuncts for stomatitis & mucositis
various medications alone or in compounded ‘magic mouthwash’ combinations
Chemotherapy adjunct for alopecia
Cryotherapy (cold caps)
Chemotherapy adjunct for myelosuppression
medications that stimulate the production of blood components
Chemotherapy adjunct for chemo-induced N/V
medications are administered before and after chemo. Some act by affecting the chemoreceptor trigger zone
Chemotherapy adjunct for chemo-induced N/V - drug classes
1) 5-HT3 receptor antagonists ﾖ dolasetron, granisetron, ondansetron and palonosetron.
2) Neurokinin-1 receptor antagonists ﾖ aprepitant and fosaprepitant.
3) Corticosteroid ﾖ dexamethasone (typically used in combination with a 5-HT3 receptor antagonist.
4) Other meds used in combination with some of the above include dronabinol (marijuana) and prochlorperazine.
Combination vs. single agent chemo
Treating cancer with a combination of chemo agents is typically more effective than using a single agent.
Using chemoagents with different toxicities/mechanisms
Can often be combined at full doses and result in higher response rates due to additive and/or potentiated cytotoxic effects and nonoverlapping toxicity to the patient.
Using chemoagents with similar toxicities
Can only be combined safely by reducing the doses of each.
Advantages of combination chemo
- Maximal cancer cell killing within the range of tolerated toxicity.
- A broader range of cancer cell lines in the heterogenous tumor population can be killed.
- The development of resistant cell lines may be delayed of prevented.
Applicability of Combination protocols/regimens
applicable to one or more specific types of cancer.
Typical Chemo Intervals
typically scheduled at intervals of about 21 days (intermittent therapy).
Why use intervals in chemo?
allow for the patientﾒs immune system to recover from the chemo and reduce the risk of infection
Antimetabolites
structurally similar to purine and pyrimidine bases and interfere with their availability by inhibiting their synthesis or competing with them in DNA and RNA synthesis. Most of the chemotherapeutic antimetabolites are either a purine or a pyrimidine analog.
Common Adverse Effects of Cancer Chemotherapeutic Agents
1) Buccal mucosa ﾖ stomatitis.
2) Upper GI tract (mouth, throat and esophagus) ﾖ mucositis.
3) Hair follicles ﾖ hair loss.
4) Bone marrow ﾖ myelosuppression that can affect white blood cells (neutropenia), red blood cells (anemia) and platelets (thrombocytopenia).
5) Small intestine (with the chemoreceptor trigger zone in the brain) ﾖ nausea and vomiting.
Origin of Chemotherapeutic antibiotics
isolated from different strains of Streptomyces fungus.
General Actions of Chemotherapeutic Antibiotics
primarily act by interacting directly with DNA and disrupting its functions
3 Specific Actions of Chemotherapeutic Antibiotics
1) interfering with RNA enzyme functions;
2) intercalating between DNA base pairs;
3) producing superoxide free radicals that cause DNA strands to break.
Adverse Effects: Anthracyclines
THE ANTHRACYCLINES CAN CAUSE IRREVERSIBLE, DOSE-DEPENDENT CARDIOTOXICITY. This is due to the effects of superoxide radicals on the myocardium. The anthracyclines also causes the usual AEs and are vesicants.
Uses: Bleomycin
treatment of testicular cancer, squamous cell carcinomas and some lymphomas
Adverse Effects: Bleomycin
BLEOMYCIN CAN CAUSE PULMONARY TOXICITY that progresses from rales, cough and infiltration to potentially fatal PULMONARY FIBROSIS. The condition is sometimes referred to as bleomycin lung. The agent can also causes most of the common AEs with the unusual exception that myelosuppression is rare with bleomycin.
MoA of Chemotherapeutic Antibiotics
1) Changes in a transport system can rapidly move the agent out of the cell following successful entry (e.g., P-glycoprotein).
2) Intracellular repair of DNA strand breaks by PARP enzymes.
Alkylating Agents
cause the alkylation (i.e., the addition of an alkyl group) to the 7-nitrogen position on guanine in DNA.
General Action: Alkylating Agents
Alkylation causes DNA strand fragmentation, interference with DNA replication and impaired protein synthesis.
Adverse Effects: ALKYLATING AGENTS - Cyclophosphamide & Ifosfamide
Unique toxicity with both agents is due to the acrolein and other metabolites that are formed along with the active metabolite phosphoramide. These toxic metabolites can cause HEMORRHAGIC CYSTITIS AND FIBROSIS IN THE BLADDER. Adequate hydration and the drug MESNA help lessen those effects in the bladder.
platinum complexes
carboplatin, cisplatin, & oxaliplatin
platinum complexes MoA
Chemical structures include platinum. The mechanism of action is similar to that of the alkylating agents and involves the formation of inter- and intra- strand cross-links
Adverse Effects: platinum complexes
All 3 agents cause the common AEs. Aggressive hydration is required with cisplatin to help prevent NEPHROTOXICITY.
Effects of Interferons
Though the exact mechanism for the reaction is not known, the effects include suppression of cell proliferation, activation of macrophages and increased cytotoxicity of lymphocytes.
Interferons
bind to cell surface receptors and this causes a series of complex intracellular reactions to take place. EFFECTS INCLUDE SUPPRESSION OF CELL PROLIFERATION, ACTIVATION OF MACROPHAGES, AND INCREASED CYTOXICITY OF LYMPHOCYTES
Effects of Microtubule Inhibitors
affect the normal formation and function of the MITOTIC SPINDLE that is involved in METAPHASE, leading to cell death.
Actions of Microtubule Inhibitors
1) formation of a dysfunctional spindle that cannot segregate the chromosomes during metaphase;
2) formation of overly stable microtubules that are nonfunctional during metaphase.
Adverse Effects: Microtubule inhibitor - Vincristine
NEUROTOXICITY - Peripheral neuropathy, paresthesias and neuropathic pain.
Tumors that are steroid hormone-sensitive may be either:
1) hormone responsive; 2) hormone dependent; or 3) both.
Hormone Responsive Tumors
tumor regresses after treatment with a specific hormone
Hormone Dependent Tumors
removal of a specific hormone causes tumor regression
Aromatase
enzyme that catalyzes the conversion of testosterone and androstenedione to the estrogens estrone and estradiol
Aromatase Inhibitors
DECREASE THE PRODUCTION OF ESTROGEN by blocking the activity of aromatase. This helps slow or stop the growth of hormone dependent tumors such as breast cancer.
GnRH Analogs
goserelin and leuprolide
Actions: Steroid hormones - GnRH (LHRH) analogs
Occupy the GnRH receptors in the pituitary. After an initial increase in LH and FSH secretion, the RECEPTORS ARE DESENSITIZED and the production of LH and FSH is inhibited. This results in DECREASED PRODUCTION OF ESTROGEN AND TESTOSTERONE
Actions: Antiandrogens
directly compete with testosterone for binding on hormone dependent androgen receptors located on the prostate gland.
Monoclonal antibody Production
produced using BIOTECHNOLOGY and are designed to INTERACT WITH SPECIFIC TARGETS in or on cancer cells and CAUSE CELLS TO STOP growing or to DIE.
Actions: Monoclonal antibodies
1) BINDING to certain cancer cell PROTEINS or surface antigens and RECRUITING CYTOTOXIC IMMUNE SYSTEM mediators to ATTACK AND KILL the cancer cells;
2) binding to certain GROWTH FACTOR RECEPTORS on the of CANCER CELLS’ SURFACE, thereby INHIBITING the cell GROWTH PROCESSES, causing cell death;
3) binding to and INHIBITING cancer cell VASCULAR ENDOTHELIAL GROWTH FACTOR, thereby PREVENTING ANGIOGENESIS necessary for the cancer cells to grow.
General Actions of Topoisomerase inhibitors
act on the essential DNA topoisomerase enzymes and cause effects that either STOP DNA REPLICATION or cause cancer cells to undergo APOPTOSIS.
Specific Actions of Topisomerase Inhibitors
1) binding to topoisomerase-DNA complexes at sites of separation and PREVENT THE REJOINING OF STRANDS; 2) binding to DNA break sites and RENDER DNA strands SUSCEPTIBLE TO IRREVERSIBLE BREAKS.
