ISAT EXAM 3
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- Agents that act in G1 phase
- Steroids Asparaginase
- Agents that act in S phase
- Antimetabolites
- What cell cycle phase does etoposide affect?
- G2 phase.
- What phase of cell cycle do taxanes affect?
- M phase
- Agents that are not cell cycle specific.
- Alkylating Agents, Anthracyclines.
- mechlorethamine
- Alkylating Agent. Nitrogen Mustard
- cyclophosphamide
- Alkylating agent. Nitrogen Mustard
- ifosfamide
- irritant. Alkylating Agent. Nitrogen Mustard.
- carmustine (BCNU)
- Nitrosourea. Nitrosureas are very lipophillic unlike nitrogen mustard so they can cross the BBB and are useful for CNS tumors.
- lomustine (CCNU)
- Nitrosourea. Nitrosureas are very lipophillic unlike nitrogen mustard so they can cross the BBB and are useful for CNS tumors.
- Cisplatin
- Alkylating Agent. Platinum analogue. Cuases myleosuppression. Nephrotoxicity, ototoxicity, and neurotoxicity.
- Carboplatin
- Alkylating Agent. Platinum analogue. Less NV, less neruotoxicity, but a lot more myleosuppression.
- Oxaliplatin
- Alkylating agent. Platinum analogue. Special sensory neuropathy that you don't see with others - intolerance to cold after infusion.
- How do antimetabolites work?
- Interfere with DNA synthesis by incorporating themselves into DNA.
- methotrexate
- antimetabolite. Folate antagonist.
- pemetrexed
- antimetabolite. folate antagonist.
- mercaptopurine
- antimetabolite. purine analgoue.
- fludarabine
- antimetabolite - purine analogue.
- cladribine
- antimetabolite, purine analog.
- Fluorouracil (5-FU)
- antimetabolite - pyrimidine analog. Commonly used in a lot of GI cancers. Toxicities are mucositis and diarr, myleosuppression.
- Cytrabine (ara-C)
- antimetabolite - pyrimidine analog. Used for hematological malignancies, lymphoma, leukemia.
- capecitabine
- antimetabolite, pyrimidine analog. prodrug to 5-FU. Can take this as an outpatient. Major tox are GI, diarr, and hand foot syndrome. Red swelling painful hands and soles of feet.
- Vincristine
- antimicrotubules - vinca alkaloids. Neuropathies with vinca alkaloids. sensory and autonomic neruopathies (paraletic illeus)
- Vinorelbine
- antimicrotubule - vinca alkaloid. Neuropathies with vinca alkaloids. sensory and autonomic neruopathies (paraletic illeus)
- Vinblastine
- antimicrotubule - vinca alkaloid. Neuropathies with vinca alkaloids. sensory and autonomic neruopathies (paraletic illeus)
- Paclitaxel
- antimetabolite - taxane. Causes hypersensitivity so have to premed.
- Docetaxel
- antimicrotubule - taxane.
- What are two side effects of docetaxel?
- edema and ascities
- Irinotecan (CPT-11)
- Topo I inhibitor. Causes diar. attenuated delayed diar. Mange it with anti-dia
- Topotecan
- Topo I inhibitor. CNS tumors, pediatric malign.
- Etoposide (VP-16)
- topo II inhibitor. Variety of solid tumors.
- Teniposide
- topo II inhibitor.
- antitumor antibiotics
- end with -rubicin except for mitoxantrone. These agents are cell cycle nonspecific and are known for their cardiotoxicity.
- bleomycin
- antitumor antibiotic. causes pulmonary tox
- dactinomycin
- antitumor antibiotic
- mitomycin
- antitumor antibiotic
- cancers that can be CURED with chemo
- Acute Lymphocytic Leukemia in children Acute myeloid leukemia Testicular Cancer Hodgkin's Disease Non-Hodgkin's Lymphoma Small cell lung cancer (limited stage)
- Malignancies for which chemo is used with curative intent.
- Breast cancer (Early stage) Colorectal cancer (Advanced stages) Osteosarcoma Ovarian cancer
- Why would you use combination chemothearpy? What are some principles for use?
- Drugs with different mechs of action Avoid overlapping tox Drugs with demonstrated activity optimal use of drug ande schedule.
- CHOP thearpy
- Cyclophosphamide, Hydroxy- daunarubicin, Oncovin, Prednisone – NHL
- This factor is over expressed in 50-80% of NSCLC
- EGFR
- What type of agent is Leuprolide and what is it used for?
- LHRH agonists. prostate cancer
- MAID thearpy
- Mesna, Adriamycin, Ifosfamide, Dacarbazine – Sarcoma
- Hormonal Thearpy for breast cancer treatment
- anti-estrogens, aromatase inhibotrs
- tamoxifen
- anti-estrogen. causes: Hot flashes Nausea Fatigue Flare reactions Endometrial cancer Thromboembolic events
- Toremifene
- anti-estrogen. used for breast cancer
- Fulvestrant injection
- anti estrogen. used for breast cancer
- Letrozole
- aromatase inhibitor. used for breast cancer.
- Anastrozole
- aromatase inhibitor. used for breast cancer
- Hormonal treatment for prostate cancer treatment
- anti-androgens, LHRH agonists
- anti-androgens are used for what type of cancer?
- prostate
- what type of drug is flutamide?
- anti-androgen
- what type of durg is bicalutamide?
- antiandrogen
- What type of agent is Goserelin?
- LHRH agonists
- What is Goserelin used for?
- prostate cancer
- Immunothearpy Bilogical response modifiers
- Malignant melanoma and CML Interferon-alfa-2a (Roferon) Interferon-alfa-2b (Intron) Interferon-alfa-N3 (Alferon) PEG-interferon-alfa-2b (PEG-Intron)
- agents used for renal cell carcinoma
- Renal Cell Carcinoma Interleukin-2 (IL-2) Aldesleukin (Proleukin)
- monoclonal antibodies
- end in -mab Gemtuzumab ozogamycin Rituximab Trastuzumab Alemtuzumab Bevacizumab Cetuximab
- Limitations to monoclonal antibody thearpy
- Large molecules have poor access to bulky tumors Slow distribution Rapid clearance of antibody by circulating tumor cells Immunogenicity (Infusion related/allergic reactions)
- Tyrosine Kinase Inhibitors (TKIs)
- Small molecule oral agents, intracellular targets
- Gefitinib (Iressa)
- EGFR Tyrosine Kinase Inhibitor. Thirdline monothearpy metastaic NSCLC
- What are 2 common adverse effects to EGFR tyrosine kinase inhibitors?
- Diarrhea, acneform rash.
- Erlotinib (Tarceva)
- EGFR tyrosine kinase inhibitor. second or third line thearpy for monothearpy NSCLC 150 mg PO QD First line treatment with gemcitabine for metastatic pancreatic cancer 100 mg PO QD
- Multikinase TKIs adverse effects
- diarrhea, nausea, acneform rash, HTN, handfoot syndrome, liver abnormalities.
- Suntinib (Sutent)
- multikinase TKI. VEGFR, PDGFR, cKIT. GIST after disease prgoression on imatinib. advanced renal cell carcinoma.
- Sorafenib (Nexavar)
- VEGFR, PDGFR, Raf Advanced renal cell carcinoma 400 mg PO BID
- Imatinib (Gleevec)
- Inhibits Bcr-Abl protein tyrosine kinase Translocation 9:22 chromosomes Inhibits Kit and PDGFR Indicated for Ph-positive ALL or CML 400-600 mg PO QD Myelosuppression, nausea, diarrhea, fluid retention, myalgias, skin rash, hepatotoxicity
- Super Gleevecs
- overcome imatinib resistance. Dasatinib (Sprycel) FDA approved June 2006 300 fold more potent than imatinib 700 mg PO BID Myelosuppression, nausea, diarrhea, edema, effusions Nilotinib (Tasigna) FDA approved 10/2007 20 to 50-fold more potent than imatinib Myelosuppression, rash, hyperbilirubinemia
- How do oral immunomodulating agents work?
- modulation of T helper cells, inhibiton of TNF-alpha, antiangiogenesis
- What type of agent is Thalidomide?
- oral immunomodulating agent
- What is Thalidomide used for?
- newly diagnosed multiple myeloma. It is used in combination with dexamethasone
- What are the side effects of thalidomide?
- teratogenciity, VTE, neutropenia, neruopathy, constipation
- What type of agent is lenlidomide
- oral immunomodulating agent
- What is lenlidomide used for?
- MDS with sympotmatic anemia, multiple myleoma
- What are the side effects of lenalidomide?
- myleosuppression, thrombosis, less neuropathy.
- What are the three factors that influence the modality of cancer treatment?
- cancer type, prior thearpy, cancer stage
- What are five ways cancer can become drug resistant (acquired mechanisms)
- Improved proficiency in DNA repair Increase in drug inactivation Decrease in cellular uptake of drug Decrease in drug activation Increase in efflux of drug
- What things can be done to help manage drug resistance? (3)
- Change Therapies Increase Dose Biochemical modulation
- What is biochemical modulation in drug resistance treatment?
- Leucovorin + Fluorouracil Cyclosporin and analogues (PSC-833) Calcium channel blockers
- What are sanctuary sites?
- CNS, Brain, very common with hematological cancers. Depending on thearpy might relapse in the CNS. Testis are another site. Leukomia relapse in testis
- How can you overcome sanctuary sites of tumors?
- high dose of chemo, high dose of MTX, local administration.
- What are 3 considerations for drug scheduling of chemo thearpy?
- dose-intensity, cell cycle kineitics and efficacy (what stage the drug works in the cell cycle), toxicity
- Name around 7 considerations for chemo that are patient related factors.
- Renal and/or Hepatic Function Age/Performance status Prior exposure to chemotherapy Nutritional status (if healthy you will have less myleosuppression) Immunocompetence
- What type of agent is Mesna?
- chemoprotectant
- How does mesna chemoprotect?
- Binds to drug and prevents it from attacking bladder wall.
- What type of drug is dexrazoxane?
- cardioprotective chemoprotectant
- This agent decreases cardiotoxicity specifically related to anthracyclines
- dexrazoxane
- What type of agent is amifostine?
- chemoprotectant - decreases nephrotox
- This agent decreases nephrotoxicity with cisplatin thearpy.
- amifostine
- What type of agent is leucovorin?
- chemoprotectant - helps replenish folates.
- This agent helps replenish folates that are missing because of MTX. It also helps alleviate mucositis and myleosuppression.
- Leucovorin
- What is myelosuppression?
- suppression of RBC (anemia), WBC (granulocy) and platelts (thromobocytopenia)
- Granulocytopenia is defined by these two lab values
- neutropenia - ANC< 500/m3 Fever > 38.3
- Name around 6 causes of nausea and vomitting
- Causes of emesis: Chemotherapy, radiation, surgery Other Drugs Obstruction Gastritis/Esophagitis Brain Metastasis Pancreatitis
- These factors infleunce emetic potential
- Drug, Dose, Schedule Prior Emetic Experience - Anticipatory N/V Alcohol Use Gender Age
- Do alcohol abusers do better or worse with N/V?
- abusers do better with N/V
- Do females do better or worse with N/V?
- Females do worse.
- Name 8 N/V drug thearpies
- 5-HT3 receptor antagonist Substitued Benzamides (metoclopramide) Phenothiazines (prochlorperazine) Butyrophenones (haloperidol) Corticosteroids (dexamethasone) Benzodiazepines (lorazepam) Cannabinoids (dronabinol) NK-1 antagonists - Aprepitant (Emend)
- What type of agent is prochlorperazine?
- N/V agent
- What type of agent is metoclopramide?
- N/V agent
- 5-HT3 receptor antagonists are useful for what?
- N/V!!!
- What type of agents are NK-1 antagonists?
- N/V agents
- what type of agent is aprepitant?
- NK-1 antagonist or N/V drug thearpy
- What is megestrol acetate used for?
- anorexia
- What are corticosteroids used for?
- anorexia AND N/V
- what are anabolic steroids used for?
- anorexia
- What is fluoxymesterone used for?
- anorexia
- What is Nandrolone decanoate used for?
- anorexia
- What types of infections cause mucositis?
- HSV, fungal.
- Why should mucositis legions be cultured?
- to r/o viral or fungal
- What types of chemo cause mucositis?
- fluorouracil, MTX, antracyclines.
- What is the etiology of mucocitis?
- radiation, chemo, infection
- What factors infouence severity of mucositis?
- drug, dose, schedule
- HOw should mucositis be managed? (five thigns)
- General mouth care Decreased oral intake nutritional supplements parenteral nutrition Pain management Antiviral therapy Antifungal therapy
- What causes diarrhea in cancer patients?
- chemo, infection.
- What are some complications from diarrhea? (3)
- Fluid and electrolyte imbalance Peri-rectal cellulitis Anorexia
- What kind of agent is loperamide?
- anti-diar
- What kind of agent is Diphenoxylate/atropine?
- anti-diar
- What is a major toxicity of Doxorubicin?
- cardiac tox
- What are some risk factors for cardiotox due to doxorubicin? (5)
- Cumulative dose > 550 mg/m2 Schedule of Administration Age Prior radiation therapy to chest Pre-existing cardiac disease
- What is a major tox of bleomycin?
- pulmonary toxicity
- What are the risk factors for pulmonary toxicity from bleomycin? (3)
- cumulative dose > 450 units Pneumonitis, interstitial fibrosis Other drugs causing pulmonary fibrosis Busulfan Carmustine Chlorambucil
- Name 3 drugs that can cause pulmonary fibrosis, and thus are risk factors for pulmonary tox with bleomycin.
- Busulfan Carmustine Chlorambucil
- This drug can cause renal tubular necrosis.
- cisplatin
- This drug causes renal tubluar obstruction
- methotrexate (MTX)
- These two drugs cause hemmoragic cystis.
- cyclophosphamide/ifosfamide.
- How can you help tubular necrosis?
- Hydration osmotic diuretic like mannitol.
- How can you help MTX tox?
- give sodium bicarb to alkalinze the urine and help eliminate MTX.
- What two types of agents cause neruopathies?
- vinca alkaloids, platinum
- What agent causes cerebellar tox??
- cytrabine
- This agent causes ototox
- cisplatin
- cremophor EL is used for what?
- hypersensitivity rxns.
- What are some late effects of alkylating agents? (s)
- leukemia/MDS
- What is a late effect of tamoxifen?
- uterine cancer
- What type of secondary malignancy is due to a late effect of cyclophosmamide/ifofamide?
- bladder
- what type of secondary malignancies are due to radiation?
- sarcoma, leukemias
- These 3 chemothearpy agents cause the late effect of infertility
- cytoxan, nitrosureas, procarbazine
- list the people who will have a greater effect on infertility (ie sex etc). order great from least
- adult men > postpubertal women > prepubertal women
- What phase of the cell cycle do Vinca Alkaloids affect?
- M phase
- what type of drug is nilutamide?
- antiandrogen
- What are 3 side effects of anti-androgens?
- gyencomastia, increased LFTS, diarrhea.
- What are LHRH agonists used for?
- prostate cancer
- Name 3 side effects of LHRH agonists
- hot flashes, tumor flare, impotence
- What should docetaxel be premed with and why?
- dexamethasone b/c edema is thought to be due to inflamm process
- Mechanism of action of topoisomerase inhibitors
- prevent DNA uncoiling
- Mechanism of alkylating agents
- interfere with DNA base pairing, leading to the strand breaks and arresting DNA replication
- Mechanism of action of Taxanes and vinca alkaloids
- Interfere with microtubule function required for cell mitosis
- Mechanism of action of antimetabolites
- block the formation and use of nucelic acids essential for DNA replication
- CD20 is overexpressed on what types of malignant and normal tissues (2)
- lymphoma and leukemia cells
- HeR2/neu is present on 25% of what type of cancer cells?
- breast cancer cells
- VEGFR is overesxpressed on what types of malignant and normal tissues?
- tumor vasculature
- How can receptor pathways of cancer cells be inhibited? (4)
- binding and neutralizing ligands occupying receptor-binding sites blocking receptor signaling within the cancer cell interfering with downstream intracellular molecules
- What are some common side effects of G-CSFs? (4)
- mild to moderate bone pain fever generalized rash injection site redness
- What is the indication for Pegfilgrastim
- Decrease the incidence of infection in patients with non-myeloid malignancies receiving chemotherapy associated with a significant incidence of febrile neutropenia.
- What are some adverse effects of Pegfilgrastim (4)
- bone pain splenic rupture adult resp distress syndrome sickle cell disease
- What is Darbepoetin alfa?
- A novel erythropoiesis-stimulating protein with two extra sialic acid-containing carbohydrate side chains.