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Pharmacologic Principles of Cancer Treatment
Pharmacology Module 2
112
Medical
Graduate
06/18/2009

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Cards

Term
What is the moa of mechlorethamine (N2 mustard)?
Definition
Alkylating Agents: Covalently bind to guanine bases of DNA and thereby interfere with normal function resulting in single- or double-stranded DNA breaks.
Term
What is the moa of cyclophosphamide (cytoxan)?
Definition
Alkylating Agents: Covalently bind to guanine bases of DNA and thereby interfere with normal function resulting in single- or double-stranded DNA breaks.
Term
What is the moa of ifosfamide (ifex)?
Definition
Alkylating Agents: Covalently bind to guanine bases of DNA and thereby interfere with normal function resulting in single- or double-stranded DNA breaks.
Term
What is the moa of cisplatin (platinol)?
Definition
Alkylating Agents: Covalently bind to guanine bases of DNA and thereby interfere with normal function resulting in single- or double-stranded DNA breaks.
Term
What is the moa of carboplatin (paraplatin)?
Definition
Alkylating Agents: Covalently bind to guanine bases of DNA and thereby interfere with normal function resulting in single- or double-stranded DNA breaks.
Term
What is a cytoprotectant that binds to acrolein and deactivates it?
Definition
mesna
Term
What is a metabolite that is excreted in the urine and can cause hemorrhage cystitis?
Definition
acrolein
Term
What is needed when a pt is exposed to acrolein?
Definition
adequate po and iv hydration
Term
what are 2 alkylating prodrugs which are converted by hepatic metabolism to several active and inactive metabolites.
Definition
cyclophosphamide and ifosfamide
Term
What drug can be nephrotoxic- Patients should maintain oral hydration. IV hydration/Mannitol should be considered at higher doses. This drug is also highly emetogenic; causes both acute and delayed nausea/vomiting?
Definition
cisplatin
Term
What class do the following drugs belong to: cisplatin, carboplatin and oxaliplatin?
Definition
platinum analogues
Term
What are derivatives of cisplatin engineered to improve efficacy and decrease toxicities?
Definition
carboplatin and oxaliplatin
Term
What class of drugs is structurally related to normal cellular components and interferes with the availability of normal purine or pyrimidine precursors by: (1) inhibiting their synthesis, or (2) competing with them in the process of DNA or RNA synthesis?
Definition
antimetabolites
Term
What agents are cell cycle specific and generally exert their effect in the S-phase of the cell cycle?
Definition
antimetabolites
Term
What aspect of dosing is important when dealing with antimetabolites?
Definition
dosing schedule
Term
The following belong to what class of drugs: fluorouracil (5fu), cytarabine (ara-c), methotrexate, gemcitabine?
Definition
antimetabolites
Term
The following 3 major moa's are found in what class of drugs: intercalate within the DNA molecule, interfere with transport process across cell membrane, and generate free oxygen free radicals?
Definition
anthracyclines
Term
Doxorubicin and daunorubicin are examples of which drug class?
Definition
anthracyclines
Term
Cardiotoxicity is a side affect of which drug class?
Definition
anthracyclines
Term
Irreversible & dose-dependent congestive cardiomyopathy which is a result of generation of free radicals which cause cardiac cell damage is a side effect of what drug class?
Definition
anthracyclines
Term
In which drug class must you monitor LVEF (left ventricular ejection fraction) routinely – MUGA (A MUGA scan (Multi Gated Acquisition Scan) is a nuclear medicine test to evaluate the function of the heart ventricles) or 2D ECHO?
Definition
anthracyclines
Term
What increases cardiotoxicity with anthracyclines?
Definition
xrt of thorax
Term
What type of additive dose limit is associated w/anthracyclines?
Definition
cumulative dose lifetime limit
Term
When prescribing anthracyclines, what is a cytoprotectant which prevents free radical formation?
Definition
dexrazoxane (zinecard) is a cytoprotectant which prevents free redical formation. liposomal doxorubicin (doxil) may also be considered.
Term
What is defined as an inadvertent extravasation can cause severe local tissue necrosis and ulceration which often requires surgical attention? With what drug class is this associated?
Definition
anthracyclines. vesicant hazard.
Term
The following toxicities are associated with what drug class: Alopecia, Myelosuppression, Mucositis (this could be a dose-limiting toxicity), Nausea?
Definition
anthracyclines
Term
What is the moa of vinca alkaloids?
Definition
mitotic inhibitors: promote de-polymerization and destabilization of tubulin.
Term
What is the moa of taxanes?
Definition
mitotic inhibitors- promote polymerization and overstabilization of tubulin.
Term
To what drug class do the following belong: vincristine, vinblastine, and vinorelibine?
Definition
vinca alkaloids
Term
To what drug class do paclitaxel and docetaxel belong?
Definition
taxanes
Term
What drug class is extensively metabolized & require dose modification in hepatic dysfunction?
Definition
vinca alkyloids
Term
What agent have different uses and toxicities despite structural similarities and MOAs?
Definition
vinca alkaloids
Term
What drug is used in a variety of hematologic and solid tumors? The main DLT (dose limiting toxicity) is neurotoxicity. Fatal if given intrathecally.
Definition
vincristine (oncovin)
Term
What drug is used in fewer cancers: lymphoma, breast, bladder, ovarian and testicular? Main DLT is myelosuppression.
Definition
vinblastine (velban)
Term
What drug is used in NSCLC and breast cancer. Causes myelosuppression and peripheral neuropathy?
Definition
vinorelbine (navelbine)
Term
Which vinca alkaloids are vesicant hazards?
Definition
all
Term
What drug is a semisyn derivative of vinblastine?
Definition
Vinorelbine
Term
What drug class are enzymes which allow the coiling and uncoiling of the DNA strands which is needed during the replication and transcription of DNA?
Definition
dna topoisomerases (topo I and topo II)
Term
The following are examples of what drug class: etoposide (vp-16)- sclc, topotecan (hycamptin)- sclc, ovarian, and irinotecan (camptosar)- colon?
Definition
topoisomerase inhibitors
Term
Which topoisomerase inhibitors are used for sclc?
Definition
etoposide (vp-16) and topotecan (hycamptin)
Term
Which topoisomerase inhibitor is used for ovarian?
Definition
topotecan (hycamptin)
Term
Which topoisomerase inhibitor is used for colon?
Definition
irinotecan (camptosar)
Term
Which topoisomerase inhibitor is generally well tolerated
and is considered synergistic with platinum analogues?
Definition
etoposide
Term
Which topoisomerase inhibitor was first approved for colorectal cancer?
Definition
Irinotecan
Term
Which topoisomerase inhibitor involves a dlt of (not myelosuppresion) diarrhea?
Definition
Irinotecan
Term
Which topoisomerase inhibitor produces severe diarrhea in some patients?
Definition
Irinotecan
Term
What might you give with irinotecan to reduce severe diarrhea?
Definition
atropine, loperamide (imodium)
Term
Which cancers are hormone dependent and respond well to hormonal manipulation?
Definition
breast and prostate
Term
What is the moa of hormonal therapy?
Definition
interact with hormonal receptors at cell membrane or within nucleus
Term
What hormone-sensitive disease can be treated with:
Oophorectomy or ovarian ablation w/ Zoladex
Antiestogens – classical antagonist (Tamoxifen)
Aromatase inhibitors – prevents peripheral
estrogen synthesis postmenopausal
women only (Femara, Arimidex, Aromasin)?
Definition
breast cancer
Term
In what 3 settings can hormonal therapy be used?
Definition
Prevention, Adjuvant, Metastatic setting
Term
What are engineered to bind to specific receptors (antigens) located on the surface of the malignant cells which are responsible for signaling cell growth and regulation?
Definition
monoclonal Abs
Term
How does monoclonal Ab binding produce antitumor effects?
Definition
in various ways: prevents receptor stimulation leading to cell growth. the binding causes the apoptosis. attracts “natural killer” cells. can fuse Moab to cytotoxic complex (“Magic bullet”).
Term
Targeted therapy involves what 2 types of inhibition and what 3rd mechanism?
Definition
Epidermal Growth Factor inhibition – Herceptin (breast), Erbitux (colon)
Tyrosine Kinase inhibition – Tarceva (lung), Gleevec (CML, GIST) Antiangiogenesis – Avastin (colon, lung, breast cancers in metastatic setting as of now)
Term
What is anc?
Definition
Absolute Neutrophil Count (ANC) = [% segs + % bands] X WBC count
Term
What occurs when a patient has a fever and a significant reduction in their white blood cells?
Definition
febrile nutropenia
Term
How should febrile neutropenia/infection pts be assessed?
Definition
Patients should be promptly assessed and appropriate empiric antibiotic therapy initiated
Term
In febrile neutropenia/infection, what factors are used to shortened the duration and lessened the degree of the WBC nadir? What are 2 specific examples?
Definition
WBC colony stimulating factors are used to shortened the duration and lessened the degree of the WBC nadir. filgrastim (Neupogen) pegfilgrastim (Neulasta)
Term
What is the most distressing symptom commonly reported by cancer patients?
Definition
nausea
Term
What are the side effects of protracted vomiting?
Definition
Protracted vomiting may lead to dehydration and electrolyte depletion
Term
How do antiemetic therapies work?
Definition
Used to block one or more of these signals and prevent or decrease nausea and vomiting.
Term
What appears to be the most sensitive signal during the first 24 hours after chemotherapy?
Definition
serotonin (5-ht3)
Term
What agents are widely used as first line agents in the prevention of chemotherapy induced nausea/vomiting? What are 4 specific examples?
Definition
5-HT3 receptor antagonists are widely used as first line agents in the prevention of chemotherapy induced nausea/vomiting. Common 5-HT3 include: granisetron (Kytril), ondansetron (Zofran), dolasetron (Anzemet), palonsetron (Aloxi)
Term
What ranking is cancer for death in the us?
Definition
#2
Term
What is the no one cause of cancer death?
Definition
lung cancer
Term
What is the definition of cancer?
Definition
a disease of cell proliferation which is characterized by a *loss of nml control mechanisms* which regulate orderly cell growth/differentiation and function
Term
What is the main problem with cancer?
Definition
Malignant cancer cells break away from the original tumor and travel in the circulatory or lymphatic systems until they are lodged in a small capillary network in another area of the body and begin to grow in the new location. (before it metastasizes it is curable. after metasasis it is treatable but not curable.)
Term
What are thre ca tx modalities?
Definition
surgery, xrt, chemo
Term
What are some pt specific faactors in chemo?
Definition
Performance status, Comorbidities / End organ dysfunction, Personal choice
Term
What is the goal of chemo?
Definition
To eradicate the malignant cells by exploiting the differences between the malignant and normal host cells while minimizing the toxic effect of normal host cells.
Term
What are disease stage considerations in chemo?
Definition
Early, Locally Advanced, Recurrent, Metastatic
Term
What are therapeutic intent considerations in chemo?
Definition
Cure vs. Palliation
Chemosensitivity of tumor cells
Term
How are chemotherapy drugs together generally used to tx most ca?
Definition
Combination chemotherapy is generally used to treat most cancers.
Term
In what time frame are chemo drugs usually given?
Definition
Chemotherapy drugs are usually given in cycles. Cycles are repeated weekly or monthly for a few months or several months with a recovery period after each treatment
Term
What is used after the definitive, local therapy (surgery) to reduce the risk of recurrence?
Definition
adjuvant
Term
What is used prior to definitive local therapy (surgery) in an attempt to shrink tumor and may make an “inoperable” tumor operable?
Definition
neo-adjuvant
Term
Why might chemo be given for metastatic disease?
Definition
to minimize the extent/size of tumor burden, pain control, palliation; weigh side effects of chemo vs. symptom management
Term
What must be considered when using chemo for recurent disease?
Definition
? Length of disease free interval. ? Same agents
Term
What might be be used for refractory disease?
Definition
drugs no longer effective; use 2nd line, 3rd line, etc
Term
What might be be used for leukemia in which bone marrow is completely infiltrated?
Definition
myeloablative-leukemia
Term
What might be used for colon, head/neck ca?
Definition
radiation sensitizer-colon and head/neck CA
Term
Chemo might also be used for prevention. this is not a question, just a pt on a slide for which i couldn't think of an adequate question.
Definition
Term
What are 2 considerations due to narrow therapeutic windows?
Definition
Importance of Dose Intensity, Dose Limiting Toxicity
Term
What is the term for Certain anatomic areas of the body do not allow drug penetration. Most notably, the blood brain barrier, allow tumor cells, but not cytotoxic drug to the enter the CNS?
In certain circumstances, chemotherapy may be given intrathecally.
Definition
Pharmacologic sanctuaries
Term
What phenomenon occurs as tumor cells may develop drug efflux pumps which remove drug from the cytoplasm?
Definition
drug resistance
Term
How are chemo agents generally dosed?
Definition
Chemotherapy agents are generally dosed using a patients body surface area (BSA) as “mg/m2”
Term
What are a few exceptions to the rule "Chemotherapy agents are generally dosed using a patients body surface area (BSA) as “mg/m2”?"
Definition
A few exceptions: Carboplatin (AUC), intrathecal doses (Doses are adjusted based on hepatic / renal dysfunction
Subsequent doses are adjusted based on toxicity experienced in previous cycle. (Important to know the toxicity profile of each agent.)
Term
Why might the Mostellar equation be used?
Definition
Chemotherapy agents are generally dosed using a patients body surface area (BSA) as “mg/m2”
Term
What is the MOA of the following drugs: Topoisomerase inhibitors, Alkylating Agents, Antimetabolites,  Anthracyclines  Mitotic Inhibitors 
Definition
these interact w/ DNA?
Term
How do classical chemo drugs usually act?
Definition
Classical chemotherapy drugs usually act by interfering with vital processes involved within the cell cycle of the cancer cell
Term
How do alkylating agents act?
Definition
Covalently bind to guanine bases of DNA and thereby interfere with normal function resulting in single- or double-stranded DNA breaks
Term
In what cells are alkylating agents active? In what cells are akylating agents most active?
Definition
Active in both cycling and resting cells; but most toxic in rapidly dividing cells.
Term
(what chemo agent increases cold sensitivity?)
Definition
(oxaloplatin)
Term
The following belong to what class of drug: fluorouracil (5fu)?
Definition
antimetabolites
Term
To what drug class does cytarabine (ara-c) belong?
Definition
antimetabolites
Term
To what drug class does methotrexate belong?
Definition
antimetabolites
Term
To what drug class does gemcitabine belong?
Definition
antimetabolites
Term
(what hazard associated with anthracyclines will burn pt's skin?)
Definition
(vesicant hazard)
Term
("red devil medicine")
Definition
(anthracyclines)
Term
What is the main dlt of vincristine?
Definition
neurotoxicity
Term
What is the main dlt of vinblastine?
Definition
myelosuppression
Term
What medication ablates ovaries thus reducing estrogen release?
Definition
zoladex
Term
What antiestrogen is a classical antagonist?
Definition
tamoxifen
Term
What breast ca tx prevents peripheral extrogen synthesis postmenopausal? What are 3 specific drugs in this category?
Definition
aromatase inhibitors: femara, arimidex, aromasin
Term
What is the moa of Herceptin (breast), and Erbitux (colon)?
Definition
Epidermal Growth Factor inhibition
Term
What is the moa of Tarceva (lung),Gleevec (CML, GIST)?
Definition
Tyrosine Kinase inhibition
Term
What is the moa of Avastin (colon, lung, breast cancers in metastatic setting as of now)?
Definition
Antiangiogenesis
Term
What ca is tx w/herceptin?
Definition
breast
Term
What ca is tx w/erbitux?
Definition
colon
Term
What ca is tx w/tarceva?
Definition
lung
Term
What ca is tx w/gleevec?
Definition
cml, gist
Term
What ca is tx w/avastin?
Definition
colon, lung, breast cancers in metastatic setting as of now
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