Oncology II - Common Cancers and Treatment Flashcards
Which parts of the body have the most rapidly dividing cells, and thus are most susceptible to side effects from chemotherapy?
GI tract (vomiting/diarrhea) hair follicles (hair loss) bone marrow (suppression)
What are two clinically valid scales used for assessment of side effects by a patient’s level of physical functioning?
Karnofsky and ECOG
What is the function of BRCA genes in healthy individuals? Mutation in these genes increases the risk of what kind of cancer?
BRCA genes function as tumor suppressor genes by repairing damaged DNA. Mutations render them ineffective, and increase a woman’s odds of breast cancer.
Describe the genetic nature of Klinefelter’s syndrome, who it effects, and the cancer risk it imposes.
Klinefelter’s syndrome affects males and occurs when an extra X chromosome is present (XXY). These men produce more estrogen than normal and are at an increased risk of breast cancer, which frequently feeds on estrogen.
How does the treatment of hormone sensitive breast cancer differ in pre- and post-menopausal women?
Since premenopausal women produce estradiol (the most potent estrogen), they receive a SERM (tamoxifen) to block the hormone dependent tumor. Post-menopausal women do not produce estradiol, and instead receive an aromatase inhibitor that blocks the production of weaker estrogens in the periphery.
Why is an aromatase inhibitor not effective for hormone sensitive BC treatment in premenopausal women?
Aromatase inhibitors do not block the production of estradiol, which feeds the tumor in pre-menopausal women.
Which SERM is indicated for BC prophylaxis, but not treatment?
raloxifene
Where is raloxifene an estrogen inhibitor? agonist?
Raloxifene is an estrogen inhibitor in the ovaries - giving it some cancer prophylactic use. It is an agonist in bone, which is why it can be used for osteoporosis. However, its agonism in the CNS and blood make it not first line - it can cause hot flashes (CNS) and clots (blood).
Which SERM is an injectable?
fulvestrant (Faslodex)
Which SERM is a prodrug that requires conversion for activation? Which enzyme does this?
tamoxifen - 2D6 (don’t take with 2D6 inhibitors)
Describe the issues associated with treating hot flashes caused by tamoxifen.
Since tamoxifen requires activation by CYP2D6, and fluoxetine and paroxetine (typically used for hot flashes) are 2D6 inhibitors, venlafaxine is preferred for initial treatment.
What are some side effects of SERMs used for breast cancer treatment or prophylaxis? What are two unique to tamoxifen?
hot flashes, vaginal bleeding/spotting, vaginal discharge or dryness, decreased libido
unique to tamoxifen - cataracts and decreased bone density (supplement with calcium and D)
Tamoxifen carries a boxed warning for increased risk of what cancer?
endometrial (acts as an estrogen agonist in the uterus)
brand name and drug class of anastrozole
Arimidex - an aromatase inhibitor
Should patients be counseled to take two doses of a SERM/AI if they miss a dose one day?
no - take as soon as you remember, but not if it is close to time for your next dose, just skip dose entirely
Which SERM is a known teratogen?
tamoxifen
How should patients be counseled for oral administration of SERMs regarding food?
These may be taken with or without food.
The first-line treatment mode for prostate cancer is (think broad) _______.
androgen deprivation therapy (ADT)
How can testosterone depletion (or chemical castration) be accomplished?
A GnRH agonist may be used in combination with an antiandrogen (for a few weeks) or a GnRH antagonist/antiandrogen alone.
If a GnRH agonist is used for chemical castration, what must be used with it? Why?
An antiandrogen must be used - since the GnRH will initially cause increased testosterone production and a tumor flare, an antiandrogen must be given until the negative feedback in the pituitary shuts off GnRH release.
What are the two most commonly used GnRH agonists?
leuprolide (Lupron depot) and Goserelin (Zoladex)
What is the most significant side effect that can be partially prevented with GnRH agonists and antagonists?
a decreased in BMD - tell patients to supplement with Ca/D
Which medication is a GnRH antagonist?
degarelix (firmagon)
What are the side effects of the GnRH agonists and antagonists?
hot flashes, impotence, decreased BMD, gynecomastia, bone pain
What cardiovascular and endocrine side effects of GnRH agonists warrant concern in select patients?
QT prolongation (a side effect of androgen deprivation), dyslipidemia, and hyperglycemia
What is abiraterone? What drug must it always be given with, and why?
Abiraterone is a CYP17A1 inhibitor, which is the enzyme responsible for a large part of the metabolic conversion of cholesterol to cortisol and DHT. Since cortisol production is blocked, prednisone is given to both replace the lost steroid and provide some negative feedback on the pituitary gland to prevent further aldosterone production.
Which classes of traditional chemotherapy agents are cell-cycle independent?
Alkylating agents (eg cyclophosphamide) Anthracyclines (eg doxorubicin) Platinum compounds (eg cis/carboplatin)
Chemotherapy is most often dosed by _______ or _______.
weight (mg/kg) or BSA
What is the Mosteller equation for BSA calculation?
sqrt [(ht in cm x wt in kg) / 3600]
What is the name of the toxic metabolite of cyclophosphamide and ifosfamide? Where does this accumulate? How can patients be protected from this adverse effect?
Acrolein is a metabolite that accumulates in the bladder, causing hemorrhagic cystitis. Since ifosfamide causes this at any dose, it is always given with mesna, while only higher doses of cyclophosphamide require mesna.
Among the alkylating agents: pulmonary toxicity, neurotoxicity, and hepatic necrosis are boxed warnings of _______, _______, and _______, respectively.
carmustine, ifosfamide, dacarbazine
While it does not have a boxed warning for pulmonary toxicity, this alkylating agent is well known to cause it.
busulfan (remember the B’s are often pulmonary toxicity - busulfan/bleomycin)
Which alkylating agent should be protected from light and turns pink when it has decomposed?
dacarbazine
Which chemotherapy drug is associated with the highest incidence of nephrotoxicity and CINV?
cisplatin (boooooo)
Other than CINV, what are the two biggest concerns with cisplatin? Which of them can be reduced with a chemoprotectant?
Nephrotoxicity and ototoxicity
Nephrotoxicity can be reduced by giving IV fluids and amifostine (ethyol).
Carboplatin is dosed using what formula? Which two parameters is it based on?
Calvert formula, based on desired AUC (usually between 2-8) and GFR + 25
What is unique about oxaliplatin toxicity?
The neuropathy associated is acute and cold sensitive. The patient should avoid cold drinks and other exposure to cold as much as possible.
_________ is a chemoprotectant for prevention of anthracycline cardiotoxicity (under brand name _________) and for treatment of extravasation (under the brand name ________).
dexrazoxane, zinecard, totect
Which chemotherapy drug is red and causes red urine discoloration?
doxorubicin
________ is capped at a maximum of 2mg in a single dose to prevent neurotoxicity.
Vincristine
Vinblastine and vinorelbine are most associated with ______ toxicity.
bone (both have B in the name)
Autonomic neuropathy associated with vincristine manifests as what side effect?
constipation
Which vinca alkaloid is a major 3A4 substrate and can cause dangerous toxicity if given with an inhibitor, such as an azole antifungal?
vincristine
How do taxanes disrupt microtubule function?
They are known as microtubule stabilizers - they disrupt the critical dynamic nature of microtubules. If a microtubule cannot change its structure by rapid assembly AND disassembly, the cell will die. Taxanes prohibit microtubules from depolymerizing..
Which class of chemotherapy should always be premedicated with an antihistamine/steroid/H2RA due to potential hypersensitivity reactions?
taxanes (except abraxane, which is albumin bound paclitaxel)
Which taxane causes fluid retention? Which premedication can help with this?
Docetaxel can cause fluid retention. Strangely, this is treated with dexamethasone premedication, which has been shown to reduce peripheral edema.. It seems that this is because the mechanism of peripheral edema, when associated with docetaxel, is due to capillary leak syndrome, which responds to steroids, even though they typically cause edema themselves.
Which chemotherapy agent has a dual MOA (topo II inhibitor and intercalator)?
bleomycin
How should etoposide capsules (VePesid) be stored?
in the fridge
The maximum lifetime dose of bleomycin is _____.
400 units
What two crucial considerations are there for IV administration of etoposide?
should not be at a concentration of more then 0.4 mg/mL due to poor water solubility
infuse over 30-60 minutes due to hypotension
What is the role of leucovorin in 5-FU therapy?
increases 5-FU efficacy by stabilizing the bond between 5-FU and target enzyme (thymidylate synthase)
3 most common side effects of pyrimidine analogs
hand-foot syndrome, diarrhea, mucositis
brand name of 5-FU
Adrucil
What genetic consideration should be taken in to account for patients on a pyrimidine analog?
a deficiency of DPD (dihydropyrimidine dehydrogenase) can increase the risk of severe toxicity
What is the treatment for overdose or toxicity due to DPD deficiency in patients receiving 5-FU or capecitabine?
uridine triacetate (vistogard)
Folate antimetabolites are active against cells in which phase of the cell cycle?
s phase - folic acid is crucial for the synthesis of purines and pyrimidines
5 boxed warnings for methotrexate
1) hepatotoxicity
2) GI toxicity
3) myelosuppressio (shocker)
4) renal damage
5) teratogenicity
What is the antidote for methotrexate overdose that rapidly decreases serum concentrations?
glucarpidase (voraxaze)
What are 5 commonly used drug classes that interact with methotrexate and decrease its clearance?
1) NSAIDs
2) salicylates
3) beta-lactams
4) PPIs
5) sulfonamides
brand names of everolimus (regular and for transplant)
Afinitor, Zortress (transplant)
drug class and unique concern associated with bortezomib
protease inhibitor - can reactivate viral infections (can be given with val/acyclovir to decrease likelihood of reactivation)
most common side effect of bortezomib
peripheral neuropathy
two most common toxicities of CAR T-cell therapy (axicabtagene ciloleucel, Yescarta)
cytokine release syndrome and neurological toxicity
bevacizumab brand name
Avastin
side effects of bevacizumab
HTN that can lead to proteinuria/nephrotic syndrome (via inhibition of blood vessel formation), heart failure, thrombosis, HA
boxed warnings of bevacizumab
GI perforation, severe/fatal bleeding
To be eligible for trastuzumab (Herceptin) use, patients must have what genetic marker?
HER2+ cancer cells
HER2 inhibitors are most commonly associated with what toxicity?
cardiotoxicity - monitor LVEF while on therapy
Cetuximab (Erbitux) is a ______ inhibitor.
EGFR
What genetic testing should be done before using cetixumab?
KRAS mutation (must be KRAS wild type to use)
most common side effect of EGFR inhibitors
acneiform rash (think EPIDERMAL growth factor inhibitor)
other skin toxicities such as SJS/TEN can occur as well
Describe the prognostic implications of the rash associated with EGFR use, and how patients should be counseled to manage it.
A rash is associated with better outcomes. Patients should avoid sunlight if possible. Topical emollients can help prevent skin peeling, and topical steroids and antibiotics may be given prophylactically to reduce skin damage and infection risk.
What are examples of cluster of differentiation (CD) inhibitors?
ritubximab, obinutuzumab, ofatumumab
CD inhibitors are associated with infusion reactions, and patients should be premedicated with _______, _______, and _______.
acetaminophen, diphenhydramine, and steroid
Pembrolizumab (Keytruda), Nivolumab (Opdivo), and Atezolizumab (Tecentriq) all target which receptor?
PD-1
Explain the role that PD-1 plays in immune function and cancer therapy.
Programmed cell death (PD) binds to PD-L1 (the ligand) and suppresses T-cell activity. Blocking this interaction upregulates T-cells, which have some capacity to recognize cancer cells as foreign and destroy them. However, massive upregulation of T-cells also causes some severe immune related toxicities (affect pretty much every system of the body).
What is the mechanism of action of ipilimumab (Yervoy)?
CTLA-4 inhibitor
What is the normal function of CTLA-4?
serves as a “brake” on T-cells, so blocking significantly increases T-cell functioning and can cause similar immune related toxicities to the PD-1 inhibitors
What is one of the most important counseling points regarding oral TKI therapy?
Bioavailability can be significantly altered by presence of/lack of food, so strict following of the recommendation for the specific TKI is important.
What genetic abnormality is present in 95% of CML patients?
BCR-ABL gene translocation
Imatinib, ponatinib, nilotinib, bosutinib, and dasatinib all target ________.
BCR-ABL
What is one side effect common in all of the oral BCR-ABL inhibitors?
fluid retention
BRAF inhibitors are used in what kind of cancer?
melanoma
BRAF inhibitors are only effective in the setting of what genetic abnormality? What class of oral TKIs are they often used in combination with?
BRAF V600E or V600K - often used with MEK inhibitors
oral EGFR inhibitors are used in this cancer
NSCLC
Most TKIs are a substrate of what enzyme?
3A4
Which oral chemo drugs must be taken with food?
capecitabine, imatinib, thalidomide, exemestane (you get exCITEd to eat)
Which oral chemo drugs must not be taken with food and separated from meals?
erlotinib, abiraterone, temozolomide, sorafenib, nilotinib, pomalidomide (EATS? NoPe!)
Which chemotherapy agent can cause blue/purple discoloration of urine?
mitoxantrone
