Term
Where did cancer rank on US causes of death in 2004? |
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Definition
2nd. 559,888 deaths. 23.1% of all deaths. |
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Term
What are the top two killer cancers for men and women? |
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Definition
Men: lung & bronchus 31%, colon & rectum 10%. Women: lung & bronchus 26%, breast 15% |
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Term
What is the definition of cancer? |
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Definition
A dz of cell proliferation which is characterized by a loss of normal control mechanisms which regulate orderly cell growth/differentiation and function. |
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Term
What makes cancer cells so problematic? |
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Definition
they have the ability to invade adjacent tissue and metastasize |
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Term
Where do these cancers like to metastasize to? Melanoma, Breast, Colorectal, Prostate. |
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Definition
Melanoma - lungs. Breast - bone. Colorectal - liver. Prostate - bone |
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Term
When is chemo tx most/least effective? |
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Definition
most effective for early or locally advanced dz. least effective for recurrent or metastatic dz. |
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Term
What are 4 patient specific factors to consider before doing chemo tx? |
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Definition
performance status - comborbities - end organ dysfunction - personal choice |
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Term
What is the general concept of chemo tx? |
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Definition
To eradicate the malignant cells by exploiting the differences b/t the malignant and normal host cells while minimizing the toxic effect of normal host cells. |
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Term
How is chemo usually given? |
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Definition
in combinations and in cycles |
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Term
What are 4 considerations when designing a chemo regimen? |
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Definition
1) select drugs which have single agent activity. 2) include drugs with different MOA and which have non-overlapping toxicities. 3) use optimal dose intensity. 4) consider using drugs which demonstrate synergy. |
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Term
When is adjuvant chemotherapy done? |
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Definition
after the definitive, local therapy (surgery) to reduce the risk of occurrence |
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Term
When is neo-adjuvant chemotherapy done? |
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Definition
prior to definitive local therapy (surgery) in an attempt to shrink tumor and may make an "inoperable" tumor operable |
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Term
When is metastatic chemotherapy done? |
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Definition
to minimize the extent/size of tumor burden, pain control, palliation; weigh side effects of chemo vs symptom mgmt |
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Term
How do tumor cells exhibit resistance to chemo? |
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Definition
develop drug efflux pumps which remove drug from the cytoplams |
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Term
Where is chemo virtually ineffective? |
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Definition
the blood brain barrier allows tumor cells, but not cytotoxic drugs, to enter the CNS. in certain circumstances, chemo may be given intrathecally. |
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Term
How are chemo agents dosed? |
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Definition
with the Mostellar equation which uses a pts body surface area (mg/m2). doses are adjusted based on hepatic/renal dysfunction or based on toxicity experienced in previous cycles (determine pt's dose limiting toxicity) |
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Term
What are two exceptions to determining dose through the Mostellar equation? |
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Definition
Carboplatin (AUC) and intrathecal doses (mg) |
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Term
Which 5 types of chemo drugs interact with DNA? |
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Definition
Alkylating agents - Antimetabolites - Anthracyclines - Mitotic inhibitors - Topoisomerase inhibitors |
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Term
Which 3 types of chemo drugs DO NOT interact with DNA? |
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Definition
Hormonal agents - Monoclonal antibodies - "Targeted" therapy |
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Term
What type of drugs coavlently bind to guanine bases of DNA and thereby interfere with normal function resulting in single or double stranded DNA breaks? |
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Definition
Alkylating agents - active in both cycling and resting cells but most toxic in rapidly dividing cells |
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Term
What type of drug are mechlorethamine (nitrogen mustard), cyclophosphamide (Cytoxan), ifosfamide (Ifex), cisplatin (Platinol), and carboplatin (Paraplatin)? |
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Definition
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Term
Which drug(s) are prodrugs which are converted by hepatic metabolism to several active and inactive metabolites; one of the metabolites, acrolein, can cause hemorrhagic cystitis so hydration is necessary, and their side effects are n/v and myelosuppression? |
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Definition
cyclophosphamide (Cytoxan) and ifosfamide (Ifex) |
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Term
What is a cytoprotectant that binds to the acrolein molecule and deactivates it? |
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Definition
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Term
Which agent can be nephrotoxic so IV hydration/mannitol should be considered and is highly emetogenic? |
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Definition
cisplatin (Platinol) - a platinum analogue, alkylating agent |
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Term
Which two drugs are derivatives of cisplatin engineered to improve efficacy and decrease toxicities? |
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Definition
carboplatin (Paraplatin) and oxaliplatin - platinum analogues, alkylating agents |
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Term
What unique adverse effect does oxaliplatin cause? |
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Definition
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Term
What type of agents are structurally related to normal cellular components and interfere with the availability of normal purine or pyrimidine precursors by inhbiting their synthesis or competing with them in the process of DNA or RNA synthesis? |
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Definition
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Term
When do antimetabolites exert their effect? |
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Definition
in the S-phase of the cell cycle |
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Term
What type of agent are fluorouracil (5FU), uracil, thymine, cytarabine (Ara-C), cytidine, methotrexate, and gemcitabine? |
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Definition
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Term
Which type of agent intercalates within the DNA molecule, interferes with transport process across cell membrane, and generates oxygen free radicals? |
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Definition
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Term
What type of agent are doxorubicin and daunorubicin? |
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Definition
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Term
What is the most severe adverse effect of anthracyclines? |
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Definition
irreversible and dose-dependent congestive cardiomyopathy which is a result of generation of free radicals which cause cardiace cell damage. |
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Term
What important factors should you consider regarding athracyclines and cardiotoxicity? |
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Definition
monitor LVEF routinely (MUGA or 2d ECHO) - radiation of thorax increases risk - cumulative lifetime dose limit - consider using dexrazoxane (Zinecard) a cytoprotectant which prevents free radical formation or lipsomal doxorubicin (Doxil) which is less cardiotoxic |
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Term
What is a vesicant hazard regarding anthracyclines? |
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Definition
inadvertant extravasation can cause severe local tissue necrosis and ulceration which often requires surgical attention. place mediport to prevent. |
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Term
What are 4 other toxicities of anthracyclines? |
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Definition
alopecia - myelosuppression - mucositis - nausea |
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Term
Which type of mitotic inhibitors promote de-polymerization and destabilization of tubilin? |
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Definition
vinca alkaloids - vincristine, vinblastine, and vinorelbine |
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Term
Which type of mitotic inhibitors promote polymerization and overstabilization of tubulin? |
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Definition
taxanes - paclitaxel and docetaxel |
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Term
Which agent is used in a variety of hematologic and solid tumors, its main DLT is neurotoxicity, and is fatal if given intrathecally? |
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Definition
vincristine (Oncovin) - a vinca alkaloid mitotic inhibitor |
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Term
Which agent is usd in lymphoma, breast, bladder, ovarian and testicular cancers, and its main DLT is myelosuppression? |
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Definition
vinblastine (Velban) - a vinca alkaloid mitotic inhibitor |
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Term
Which agent is used in NSCLC and breast cancer and causes myelosuppression and peripheral neuropathy? |
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Definition
vinorelbine (Navelbine) - a vinca alkaloid mitotic inhibitor |
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Term
What adverse effect do all vinca alkaloid mitotic inhibitors have? |
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Definition
vesicant hazards and require dose modfication in hepatic dysfunction |
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Term
What are DNA topoisomerases? |
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Definition
enzymes which allow the coiling and uncoiling of DNA strands which is needed during the replication and transcription of DNA |
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Term
What type of agent are etoposide (VP-16), topotecan (Hycamptim), and irinotecan (Camptosar) and what cancers are they used for? |
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Definition
topoisomerase inhibitors. VP-16 for SCLC - Hycamptim for SCLC, ovarian - Camptosar for colon |
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Term
Which agent is generally well tolerated and considered synergistic with platinum analogues? |
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Definition
etoposide - a topoisomerase inhibitor |
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Term
Which agent was first approved for colorectal cancer, DLT is myelosuppression, it produces severe diarrhea in some pts and atropine is used as a premedication? |
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Definition
irinotecan - a topoisomerase inhibitor |
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Term
What are three types of hormonal therapy used to treat breast cancer? |
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Definition
1) oophorectomy or ovarian ablation with Zoladex. 2) Antiestogens - classical antagonist (Tamoxifen). 3) Aromatase inhibitors - prevent peripheral estrogen synthesis in postmenopausal women only (Femara, Arimidex, Aromasin) |
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Term
Which agent used for hormonal breast ca tx can only be used for 5 years? |
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Definition
Tamoxifen, an entiestogen. after 5 years it causes breast cancer |
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Term
What type of agents are engineered to bind to specific receptors located on the surface of malignant cells which are responsible for signaling cell growth and regulation? |
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Definition
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Term
How does the binding of monoclonal antibodies produce antitumor effects? |
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Definition
prevents receptor stimulation which leads to cell growth - binding causes apoptosis - attracts "natural killer" cells - can fuse moab to cytotoxic complex ("Magic bullet") |
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Term
Which type of targeted therapy are Herceptin (breast), Erbitux (colon, head/neck), and Vectibix (colon)? |
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Definition
epidermal growth factor inhibition |
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Term
What type of targeted therapy are Tarceva (lung, pancreas) and Gleevec (CML, GIST)? |
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Definition
tyrosine kinase inhibition |
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Term
What type of targeted therapy is Avastin (colon, lung, breast, brain in metastatic setting)? |
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Definition
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Term
When does a pt's ANC usually reach its lowest level? |
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Definition
about 7-8 days after treatment. <0.5 prone to serious infection - neutropenic pxns |
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Term
When does febrile neutropenia occur? |
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Definition
when a pt has a fever and a significant reduction in their WBCs. pts should be promptly assessed and empiric abx tx started |
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Term
What are filgrastim (Neupogen), short acting qd, and pegligrastim (Neulasta), longer 2wks, used for? |
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Definition
WBC colony stimulating factors used to shorten duration and lessen degree of WBC decline |
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Term
What is the most distressing symptoms commonly reported by chemo pts? |
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Definition
nausea. protracted vomiting may lead to dehydration and electrolyte depletion |
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Term
What are Compazine and Phenergan used for? |
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Definition
at home antiemetics (PO or PR) |
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Term
What is used on days 1, 2, and 3 to prevent n/v? |
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Definition
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Term
What is the most sensitive signal during the first 24hrs after chemo and what is used to prevent it from causing n/v? |
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Definition
serotonin (5-HT3) - 5-HT3 receptor antagonists used IV 1st line to prevent n/v. |
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Term
What are four common 5-HT3 receptor antagonists? |
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Definition
Granisetron (Kytril) - ondansetron (Zofran) - dolasetron (Anzemet) - palonsetron (Aloxi) |
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