cancer chemotherapy Flashcards
benign vs malignant
malignant capable of invading surrounding tissue
benign confined to its original location
causes of cancer
1) environmental exposure eg UV light, radiation
2) verse’s
3) oncogenes
4) tumour suppressor genes
treatmetns
surgery
radiotherapy
cehmotheraory
chemotherapy
once cancer metasies chemo required for effective cancer managment
what do cancer drugs vary by
- chemical composition
- route of administration
- type of cancer targeted
- side effects
chemotherapy approaches
primary induction chemo
neoadjuvant chemo
adjuvant chemo
primary induction chemo
administed in its with advance cancer
no alternative tx
neoadjuvant chemo
its with localised therapies where alternatives are not as effective
adjuvant chemo
as an adjuvant to local therapy
effective in prolonging both disease free and overall surviial
therapeutic index
Therapeutic index is the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50)
want a large therapeutic index
what is needed for total cell kill
early diagnosis and tx
combination chemo
intermittent regimens
adjuvant and neoajuwant
what do chemotherapeutic agents
kill a constant proportion of tumour cell population, rather than a constant number of cells after each dose
solid vs disseminated cancer
solid cancer
- have a low growth fractions thus respond poorly to chemo and need surgical removal
disseminated
high growth fraction and respond well to chemo
cell cycle specific drugs
exhert action on cells traversing the cell cycle
CCNS cells
can sterilise tumour cells whether cycling or resting in G0
CCNS vs CCS
non specific able to block more cells as they are non specific
what can alkylating agents o
CCNS
- transfer alkyl groups to nucleophilic sites on DNA bases (form highly reactive carbonium ion)
- cross linkage, abnormal base pairing, DNA strand breakage
what can alkylating agents lead to
can alter healthy cells as interferes with cell cycle
lead to toxicity of other cells themselves
increase risk of second maliganies
what is often given with alkylating agents
antiemetics
alkylating drugs - examples
buluslfan
- control tumour burten
lomustine - BBB,
decarbaizine
resistant to agents - what to do
- increase activity of DNA repair enzyme
- increase metabolic inactivation of the drug
- decrease influx of the drug
platinum analogues CCNS
thought to exhort cytotoxic effect similar to alkylating agents - form platinum complexed intrastrand and inter strand cross link DNA damge inhibits cell proliferation
cisplatin
highly bound to plasma protein
poor for BBB
extensively cleared by kidney and excrete slow
adverse effects
emesis
nephrotoxicity
p
antimetabolites and type
CCs
acts on intermediary metabolism of proliferating cells
interferes with DNA/RNA growth by substituting for the normal building blocks of RNA/DAN
eg folate anatagonist - methotrexate
examples of antimetaboltes
folates
purine
prymidine
…. antagonists
folic acid antagonist
methotrexate
- interferes with formation od DNA RNA and cellular proteins
prolongs inhibitor effect as her to metabolise
immunosuppressive, cytotoxic and anti inflammatory
purine anatagnost
6 mercaptopurine
must be metabolised into active form
alters synthesis of DNA/rNA
nausea
vomiting
pain abdomanal
pyrimidine anatagnoist
flurouracil
requires activation to interfere with DNA synthesis
short half life
nausea, vomiting, headache, mood disorder
vinca alkaloids and what type of drug are they
CCS
inhibits tunilin proliferation
microtubules not assembles
cell death from mitosis arrest
eg vincacrystine
vincristine main dose limiting toxicity
neurotoxicity
taxanes and type of drug
CCS
Enhance tubular polymerisation
inhibition of mitosis and cell division
eg palcitaxel
paclitaxel
used in slid tumours
dose reduction required in pts with liver diseases to prevent accumulation
antitumoru antiiotics
abnormality in the cell proliferation
- block synthesis, DNA strand scission, interfere with cell repliation
doxorubicin
generates free radicals leading to cardiotoxiciyt
hormones and anatagonists
glucocorticoids -
estrogens - antagonists of androgens
estrogens antagonists - ER modulators
what is given to its with bone metastats
bisphosphonates
slow down rate of growth of bone crystal
reduce morbidity by reducing skeletal vents
when does metastasis in skeleton occur
in its with multiple myeloma and metastatic breast prostate, thyroid cancer
drug combination
provide maximal cell kill within a range of toxicity tolereted by the host for each drug without dose comprmose
drug resistance
- some tumours exhibit primary resistance
- acquire resistance develops in response to exposure to a given anticancer agent
