Lecture 9 - Antineoplastic Agents Flashcards
name a cancer that does not form a tumor mass
leukemia
list some factors that are suggested as contributing to causing cancer
- life style factors (smoking, diet)
- genetic factors (oncogenes, defective tumor-suppressor genes)
- environmental factors (UV radiation, pollution)
- chemical factors (asbestos, some medications)
- viruses (ex. HPV causes cervical cancer)
what do high numbers in staging mean
indicates more extensive, serious disease and a poorer prognosis
AJC staging
stave 0-IV
TNM system
T = tumor size (0-4) N = lymph node involvement (0-3) M = metastases (0-1)
common treatments for cancer
- surgery
- radiation therapy
- chemotherapy
surgery may be necessary to determine what?
- tumor size
- extent of metastases to determine staging or prognosis
Describe radiation
the use of ionizing radiation to kill cancer cells and reduce tumor mass
What is the goal of radiation?
to harm as many cancer cells as possible while limiting damage to the surrounding healthy tissues so it is given in many sessions to allow the healthy tissue to recover between sessions
Radiation can be used to treat most solid tumors including ?
those of the brain, breast, lung, cervix and stomach
What does the amount of radiation used depend on?
- type of cancer
- proximity of sensitive tissues or organs
- constitution of the patient (i.e. how healthy the patient is)
What is chemotherapy?
- involves treatment with drugs which can destroy cancerous cells
- chemotherapy usually refers to the use of cytotoxic drugs which affect rapidly dividing cells in general (so chemotherapy will also harm healthy tissues, especially those with a high replacement rate like the lining of the intestine)
- although these drugs are not specific for cancerous cells, some specificity is achieved since normal cells are able to repair DNA damage while cancerous cells usually cannot.
Why is combination chemotherapy used?
- to achieve synergy between some of the patients
- to reduce the possibility of resistance developing
- to reduce dose-related adverse effects
Chemotherapy drugs are usually administered under a plan known as a _____
protocol
What does the protocol define?
- drugs and doses used
- clinical monitoring required
- clinical endpoints as well as contingency plans (plan B) to be used as indicated by the patient’s progress and monitored parameters
Most drug doses are based on ______ _____ ____
body surface area
What are most common routes of admin of chemotherapy?
- IV
- oral
- sometimes intrathecal route is used in order to get the agent across the BBB but this route is absolutely CI for a number of antineoplastic drugs most notably the Vinca alkaloids
Vinca alkaloids never administered through ______ route
intrathecal
why might oral be better than IV
-pt can be at home, decreases costs and side effects
what are some common groups of drugs related to managing the symptoms of cancer
- antiemetics
- analgesics
- hematopoietic growth factors
what’s the difference between side effects and adverse effects?
Side effects: we can explain it based on receptor binding
Adverse effects: don’t know why it happened, come out of nowhere
how do alkylating agents work?
inhibit DNA replication by causing cross-linking and abnormal base pairing of the DNA strands.
prototype agent of alkylating agents
mechlorethamine or nitrogen mustard
alkylating agents are quite ____
toxic
How can cancer cells become resistant to alkylating agents?
through increased ability to repair DNA lesions, decreased permeability to the agents or increased production of glutathione which reads with the alkylating agent
why do we do cancer treatment in cycles
to allow the body to recover
What are adverse effects seen with alkylating agents?
- myelosuppresion with granulocytopenia
- thrombocytopenia
- anemia
- nausea/vomiting
- alopecia (reversible)
List some alkylating agents
a) nitrogen mustards (cyclophosphamide)
b) alkyl sulfonates (busulifan)
c) nitrosureas (carmustine, lomustine)
d) triazenes (dacarbazine)
What are Antimetabolites?
Structural analogues of naturally occurring substrates for biochemical reactions occurring in the body.
Several of them act as false substitutions in the production of nucleic acids and interrupt and stop the replication process.
List some antimetabolites
a) Folic acid analogs (methotrexate)
b) Purine analogs (mercaptopurine)
c) Pyrimidine analogs (%-FU, cytabarine)
Describe antibiotics for cancer treatment
Most of the antitumor antibiotics are obtained form Streptomyces species through fermentation process.
These agents act by intercalation or by sliding between DNA base pairs and inhibiting DNA synthesis.
List some examples of antitumor antibiotics
a) Anthracyclines (epirubicin, doxorubicin)
b) Miscellaneous (bleomycin, dactinomycin, mitomycin)
Describe Vinca alkaloids
The vinka alkaloids prevent formation of the mitotic spindle and stop cell division
List some plant alkaloids
a) Vinca alkaloids (vinblaastine, vincristine, vindesine)
b) Podophyllotoxins (Etoposide, teniposide)
c) Taxanes (docetaxel, palictaxol)
Describe the podophyllotoxins
; the podophyllotoxins inhibit topoisomerase an enzyme that is necessary for RNA transcription
Describe the Taxanes
The taxanes stabilize microtubules thereby prohibiting cell division
List some hormones that can be used in chemotherapy
a) Androgens (Testosterone)
b) Antiandrogen (Flutamide)
c) Estrogens (diethylstilbestrol)
d) Anti-estrogens (Tamoxifen)
e) Corticosteroids (dexamethasone, prednisone)
Describe platinum compounds
These drugs act in a similar manner as the alkylating agents and the group includes cisplatin and carboplatin
Cells with high turnover rates are more sensitive to chemotherapy toxicity. List some examples
- bone marrow
- mucous membranes
- hair follicles
- therefore the most common toxicities include myelosuppresion, mucositis and alopecia
- these are considered acute and self-limiting
myelosuppression is also known as ?
bone marrow suppression
The extent of myelosuppresion is ____-related
dose
Which drugs cause little or none myelosuppresion?
vincristine
Which drugs can can cause severe myelosuppresion?
- carmustine
- cytarabine
- doxorubicin
- paclitaxol
Generally myelosuppresion leads to 3 effects: What are they?
- neutropenia
- thrombocytopenia
- anemia
What does neutropenia predispose the patient to?
development of serious infections
Neutropenia
reduction in the neutrophil white blood cells
Thrombocytopenia
Reduction in number of platelets
What does thrombocytopenia cause?
can lead to bleeding
Why is anemia secondary to chemotherapy not as common?
due to the long lifespan of erythrocytes (which is 120 days)
When is the onset of myelosuppresion after starting treatment?
usually 7-10 days after treatment
When are the cell counts the lowest after starting treatment?
10-14 days after treatment.
When does recover of the cell counts occur?
recovery usually takes 2-3 weeks, that’s why we usually do cycles of 3 weeks
What can we use to increase the rate at which the neutrophil count recovers?
G-CSF (filgrastim)
What can giving G-CSF (filgastim) prevent?
febrile neutropenia, which usually indicates an infection, and may allow chemotherapy to continue at full doses and without delays in the treatment schedule
______ promotes the production of RBC and may prevent or correct anemia and the fatigue which accompanies it
Erythropoietin
What will increase the risk of n/v in patients getting chemo?
a history of motion or pregnancy-related nausea, female gender, fatigue, age (<50 years) and lower performance status (general health)
What are the 3 categories of N/V?
- acute
- anticipatory
- delayed
Describe Acute N/V
-Symptoms usually begin 1-2 hours after administration of an emetogenic chemotherapy drug, peak after 4-6 hours then begin to subside after 12-24 hours.
What is acute N/V due to?
-Acute nausea and vomiting appears to be due to stimulation of the chemoreceptor trigger zone (CTZ) through serotonin release.
What types of drugs are good for chemotherapy induced N/V?
- selective serotonin antagonists (ondansetron or granisetron)
- corticosteroids (dexamethasone)
Describe anticipatory nausea
- nausea triggered by stimuli associated with the therapy such as smell or sight of hospital
- psychologically induced symptom
How is anticipatory nausea best managed?
- relaxation techniques
- attention diversion
- aromatherapy
- anxiolytics like lorazepam
What is the best prevention strategy for anticipatory nausea?
ensuring good acute phase control!
Describe delayed nausea
- begins at least 24 hours after chemotherapy administration
- can persist for up to 2-5 days and the mechanism is not understood
What agents are likely to cause delayed nausea?
usually seen with the use of highly emetogenic drugs like cisplatin, carboplain, epirubicin, melphalan
Why are mucous membranes sensitive to antineoplastic drugs?
bc they contain rapidly dividing cells
40% of patients getting 5-FU will have _____
diarrhea
5-FU with ______ can cause severe diarrhea and deaths have been reported
irinotecan (new agent for colorectal cancer)
What drugs can cause constipation?
vincristine (if they’re also taking narcotics for pain management or ondansetron for N/V, this will add to constipation)
Mucositits is experienced by about 40% of patients and common with what 3 drugs?
- 5-FU
- methotrexate
- doxorubicin
Describe the presentation of mucositis
- usually starts with redness and burning around the lips and mouth
- then proceeds to ulcerations on buccal mucosa, lipids, floor of the mouth and tongue
non-pharms for mucositis
- good oral hygiene
- salt/baking soda mouth rinses can help
- antibacterial lozenges may help
What is extravasation?
when a drug is given IV and it is inadvertently infused into tissue
*a number of antineoplastic drugs are vesicants and will do severe damage to tissues.
Most vesicant extravasations will cause _____ pain although delayed rxns have been reported.
immediate
What can extravasation cause?
significant tissue injury including ulceration or necrosis and repair may require plastic surgery
List some vesicant antineoplastic drugs
- dactinomycin
- doxorubicin
- mechlorethamine
- paclitaxol
- vincristine
- vinblastine
What drugs associated with alopecia?
- cyclophosphamide
- 5-FU
- doxorubicin
- vincristine
- epirubicin
- bleomycin
- paclitaxol
When does hair loss begin and peak after treatment?
- beings 7-10 days after treatment
- peaks after 1-2 months
When does hair start to re-grow?
about a month after Tx is stopped
*new hair can be different in color or texture
Which drugs can cause severe skin dryness and itch and sensitivity to sunlight ?
A number of drugs including vincristine and 5-FU
Describe pulmonary toxicity
- generally irreversible
- may be fatal
Pulmonary toxicity is highly associated with _______
bleomycin
What are early signs and symptoms of pulmonary toxicity?
- shortness of breath
- non-productive cough
What drugs are associated with cardiac toxicity?
anthracycline antibiotics (doxorubicin, epirubicin, mitoxantrone and daunorubicin)
Risk of cardiac toxicity increases with ??
increasing cumulative lifetime dose
What is the recommended lifetime exposure of doxorubicin?
450-500mg/m^2
What is cardiac toxicity due to?
tissue damage from the generation of free radicals with the simultaneous suppression of the enzymes which protect cells from free radical damage
_________ is a cardioprotective drug which may be useful to patients at risk of developing cardiotoxicity
Dexrazoxane
What drugs are associated with neurotoxic adverse effects?
- Vinca alkaloids (vincristine, vindesine, and vinblastine)
- Platinum compounds cisplatin and carboplatin)
With vincristine and vinblastine, the extent of neurotoxicity is related to the total _______ _____ and occurs most frequently in patients over ___ years of age.
cumulative dose
40
Describe the symptoms of neurotoxic effects
- numbness of hands and feet
- gait disturbances
- severe motor weakness (severe cases)
If drug causing neurotoxic effects is not stopped early enough, some of these may be _______
reversible
_______ administration of any of the vinca alkaloids will result in death of the patient
Intrathecal
What is the neurotoxicity of the platinum compounds like cisplatin thought to be due to?
demyelination and is manifest by a sensory disturbance with a “stocking” and “glove” distribution
*may be permanent or last for several years following treatment
__________, usually seen as tinnitus is also seen with cisplatin
Ototoxicity
What drugs are associated with nephrotoxicity?
- cisplatin
- ifosfamide
- methotrexate
How can we lessen the damage caused by cisplatin?
by aggressively hydrating the patient prior to treatment and administration of IV mannitol, an osmotic diuretic
Hemorrhagic cystitis is a bladder toxicity seen after with _________ or _______.
cyclophosphamide or ifosfamide
What is the metabolite of cyclophosphamide or ifosfamide which irritates the mucosa and starts the bleeding?
acrolein
How do we prevent hemorrhagic cystitis?
Aggressive hydration prior to treatment and administration of Mensa which is a drug that binds to acrolein and helps prevent the problem
Infertility can be an adverse effects with certain drugs. Is it temporary or permanent?
can be either
What drugs have high carcinogenic risk?
topside, melphalan, mechlorethamine
Most antineoplastic agents are Category D for pregnancy. Which one is Category X?
methotrexate
