Principles of Chemotherapy Flashcards
(45 cards)
Define growth fraction.
the proportion of cells in a tumor that are actively involved in cell division
How does growth fraction impact our management of tumors?
- it is the proportion of cells in a tumor that are actively involved in cell division
- the larger the tumor, the smaller the fraction due to vascular and oxygen constraints
- therefore, tumor debunking increases the growth fraction, making the tumor more vulnerable to chemotherapy and radiation
Define generation time.
the length of the cell cycle, from one M phase to the next
For a given cell type, which phases of the cell cycle are constant and which vary?
S and M are relatively constant whereas G1 and G2 vary
Chemotherapy and radiation kill tumor cells by what order of kinetics and what does this mean?
first-order kinetics, meaning each dose kills a constant fraction of tumor cells rather than a constant number
Why do we use many small doses of chemotherapy or radiation rather than a large, 1 time dose?
- several intermittent doses are more effective since these therapies work via first-order kinetics and kill a constant fraction rather than constant number of tumor cells
- furthermore, this method reduces side effects
Which kinds of chemotherapeutic agents are more useful in tumors with a low growth fraction? Which are more useful in tumors with a high growth fraction?
- those that are cell cycle nonspecific are effective in tumors with a low growth fraction
- those that are cell cycle specific are effective in tumors with a larger growth fraction
Describe the mechanism of action and primary toxicities of alkylating agents. Give an example or two of specific drugs.
- they bind and cross-link DNA inter strand, intrastrand, or to proteins, thus preventing replication and transcription
- they are likely to cause hemorrhagic cystitis, alopecia, and nephrotoxicity
- includes cyclophosphamide, ifosfamide, and melphalan
Describe the mechanism of action and primary toxicities of alkylating-like agents. Give an example or two of specific drugs.
- they cross-link DNA strands in an interrstrand fashion
- they are likely to cause nephrotoxicity, neurotoxicity, and myelosuppression
- includes cisplatin, carboplatin, and doxorubicin
Describe the mechanism of action and primary toxicities of antibiotic chemotherapies. Give an example or two of specific drugs.
- they interfere with DNA replication through free radical formation and intercalation between bases
- they have varying toxicities
- includes bleomycin and actinomycin D
Describe the mechanism of action and primary toxicities of antimetabolite chemotherapies. Give an example or two of specific drugs.
- they block the enzymes required for DNA synthesis, thus they are most active in the S phase of the cell cycle
- likely to cause GI, myelosuppression, dermatologic, and hepatotoxicities
- includes MTX and 5-FU
Describe the mechanism of action and primary toxicities of mitotic inhibitors. Give an example or two of specific drugs.
- work by inhibiting microtubule assembly
- likely to cause myelosuppression
- includes vincristine, vinblastine, and paclitaxel
Describe the mechanism of action and primary toxicities of topoisomerase inhibitors. Give an example or two of specific drugs.
- inhibit topoisomerase, resulting in DNA strand breaks
- likely to cause myelosuppression, alopecia, and GI side effects
- includes etoposide and topotecan
Which blood cell types are most susceptible to the myelosuppressive effects of chemotherapy?
- erythroid cells
- neutrophils
- megakaryocytes
What is the difference between a sequential chemotherapeutic blockade and a concurrent blockade?
- sequential refers to the use of two or more drugs that block sequential enzymes in a single biochemical pathway
- concurrent refers to the use of two or more drugs that attack parallel biochemical pathways leading to the same end product
What is adjuvant chemotherapy?
a course of combination chemotherapy that is given in a high dose to patients who have no evidence of residual cancer after radiotherapy or surgery with the purpose of eliminating any residual cancer cells
What is neoadjunvant chemotherapy?
a course of chemotherapy that aims to eradicate micro metastases or to reduce inoperable disease to prepare patients for surgery and/or radiotherapy
What is induction chemotherapy?
a combination chemotherapy given in a high dose to cause remission
What is maintenance chemotherapy?
a long-term, low-dose regimen given to a patient in remission to maintain the remission by inhibiting the growth of remaining cancer cells
In brief what are adjuvant, neoadjuvant, induction, and maintenance chemotherapy?
- adjuvant is given in high dose after radiation or surgery to eliminate residual cancer
- neoadjuvant is given prior to radiation or surgery to eliminate micro metastases or reduce inoperable disease
- induction is high dose chemo used to induce remission
- maintenance is long-term, low-dose chemo used to maintain remission by inhibiting growth of residual cancer
How do SERMs affect estrogen signaling?
SERMs bind estrogen receptors and allow them to bind to chromosomes but inhibits their ability to activate cell metabolism when they do
What is anastrozole?
an aromatase inhibitor which suppresses intratumor and plasma estrogen levels
What is letrozole?
an aromatase inhibitor which suppresses intratumor and plasma estrogen levels
What is the major side effect of aromatase inhibitors?
they are associated with bone loss secondary to the induced hypoestrogenic state
