DSA antineoplastic agents, Linger, Part I Flashcards
What are the alkylating agents
cyclophosphamide
ifosfamide
busulfan
cisplatin
What are the antimetabolites
methotrexate
fluorouracil 5
mercaptopurine
what are the vinca alkaloids
vinblastine and vincristine
what are the taxanes
paclitaxel
what are the epipodophyllotoxins
etoposide
what are the antibiotic natural products
doxorubicin and danuorubicin
what are the anthracenediones
belomycin
what are the enzymes used for anit-neoplasia
L asparaginase
pegaspargase
What are the “-nibs”
protein tyrosine kinase inhibitors
like imatinib
what are the monoclonal Ab
rastuzumab
what are the rescue agents
leucovorin and mesna
what are the drugs to minimize neutropnia
filgrastim and pegfilgrastin
What is the serotonin antagonist
ondansetron
what cancers are curable with chemo
ALL, AML, Ewing Sarcoma Gestational trophoblastic carcinoma Hodgkin, non hodgkin, burkitt, diffuse large cell follcular mixed cell lymphoblastic rhabdomyosarcoma testicular carcinoma Wilms tumor
what viruses can lead to what types cancer
Hep B and C– hepatocellular
HIV– hodgkins and non-hodgkins
HPV– cervical and head and neck
Ebstein-barr virus – nasopharyngeal
What is Primary Induction therapy
1st Tx given
Neoadjuvant therapy
Tx as first step to shrink tumor beofre primary treatment is given
(type of induction therapy)
what is adjuvant therapy
additional cancer Tx given after primary Tx to lower the risk that the cancer will come back
When do you use primary induction chemotherapy
with advanced cancer with no other alternative Tx options
why is chemo commonly used as an adjuvant therapy
to reduce incidence of both local and systemic recurrence
What is G1 phase cell cycle
precedes DNA synthesis
cell makes components to make DNA
What is S phase cell cylce
DNA synthesis
What is the G2 phase
synthesis of components for cell division
What is the M phase
cell divides into 2 daughter G1 cells
each daughter cell may re-enter cell cycle or pass into nonproliferative stage
What controls the transitions in cell cycle
activity of specific cyclin dependent kinases (CDKs) which ar activated by small regulatory proteins called cyclins and can be inhibited by other proteins like p16 and p53 (tumor suppressors)
What does cell cycle specific mean
agents that are cytotoxic for cells during specific phases of the cell cycle
what does cell cycle nonspecific mean
agents that are cytotoxic regardless of whether the cells are cycling or resting in G0 compartment
what drug classes are cell cycle specific
antimetabolites epipodophyllotoxins antitumor antibodies taxanes vinca alkaloids camptothecins
what are the cell cycle nonspecific drug classes
alkylating agents antimetabolites (cladribine) antracyclines antitumor antibiotics platinum analogs
What are the S phase metabolites
antimetabolites: capecitabine clofarabine cytarabine fludarabine 5-fluoro uracil gemcitabine 6- merccaptopurine methotrexate 6-thioguanine
what drug inhibits S-G2 phase
etoposide
What drug and its class inhibits G2-M phase
bleomycin (antibiotic)
what are the taxanes and what phase do they inhibit
paclitaxel
docetaxel
M phase
what are the vinca alkaloids and what phase do they inhibit
vinblastine
vincristine
vinorelbine
M phase
what are the camptothecins and what phase do they inhibit
S phase
which antitumoe antibiotics are not cell cycle specific
dactinomycin and mitomycin
majority of cells in center of solid tumor are in what phase and why
G0 because of bad vascularization and absence of nutrients
low growth fraction
antineoplastic tumors work better on high or low growth fraction
high
why is chemo effective for burkitt lymphoma
because have high growth fractions close to 100% so drugs work
when is antineoplastic chemo indicated
disseminated neoplasms that are not ammenable via surgery
how do antineplastic drugs kill (kinetics)
log
first order kinetcs that a given dose will kill a constant fraction of cells
what are pharmacologic sanctuaries
regions where tumor cells are less susceptible to antineoplastic agents
what are the main sheculdes of administration chemo drugs
intermittent high dose therpay and continuous infusion
why is intermittent high dose therapy most ocmmon form of anticancer agent administration
allows recovery of normal tissues
when is continuous infusion used
when the drugs are rapidly metabolized or excreted
cell cycle specific more useful this way
what are common routes administration of the antineoplastic drugs
IV and PO
what term describes: “ each drug used in combination therapy should hace some individual therapeutic activity and should be used at maximal toelration based on individual
efficacy
what is optimum scheduling in administration
intensitve intermittent schedules of drug treatment should allow the shortest time required for recovery of most sensitive target tissue (usually bone marrow) from the acute toxic effects of antineoplastic agents
what is repeated exposure
several cycles of treatment should be given
What are problems with chemo
drug resistance
toxicity
tolerance adverse effects
what is primary resistance and how did that occur
absence of response on first expousre form resitance thought to be due to genomic instability assoc with development of most cancers
what are mech of resistance to single agents
decreased drug transport into cells
reduced drug affinity
increased expression of enzyme that inactivates drug
increased expression of DNA repair enzymes for drugs that damange DNA
What causes an multi-drug resistant phenotype
increased expression MDR1 gene which encodes cell surface transporter glycoprotein (P glycoprotein)
P glycoprotein pump is ATP dependent
What drugs may inhibit the P glycoprotein transporter
Ca Ch blockers like verapamil
what areas of normal cells are attacked by chemo drugs
high growth areas
bone marrow, GI, hair follicles, buccal mucosa, sperm forming cells
what are common adverse effects of chemo
severe vomiting, nausea, stomatis, alopecia
myelosuppression, predisposition to infection and impaired wound healing
azoospermia sometimes
developmental growth of children may be depressed
when do blood counts reach their low post Tx? cycle timing?
10-14 days and recover by day 21 and normal by 28
treatment is every 21-28 days
how is neturopenia, thrombocytopenia and anemia Tx from Tx with chemo drugs
the GM CSF and G CSF drugs
oprelvekin- thrombocytes
erythropoeitin- RBC
where is vomitin controlled
2 medullary centers
comiting center and chemoR trigger zone
Which drugs cause severe emesis
cisplatin, dacarbazine, doxorubicin, mechlorethamine
what drugs have minimal emesis
methotrexate and fluorouracil
what are the main anti-emetics used to depress vomiting adverse effect
ondansetron, serotonin antagonist
the chemo drugs work on what vomiting medullary center
the chemoR trigger zone which releases NT that act on vomiting center
what is stomatitis
inflammation of oral mucosa
what drugs cause most profound alopecia
cyclophosphamide, dactinomycin, doxorubicin, paclitaxel and vincristine
what agent is used to decreased bone destrcution in metastatic diseases in the bones
bisphosphonates inhibit osteoclast action and bone resorption and may be used to delay time to first skeletal complication
