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135 Cards in this Set
- Front
- Back
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mortality due to cancer
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554,000 people
23.1% of deaths |
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top 3 cancers for men
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prostate 29
lung/bronchus 15 colon/rectum 10 |
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top 3 cancers for women
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breast 26
lung/bronchus 15 colon/rectum 11 |
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definition of tumor
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abnormal growth of cells
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benign tumor
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does not invade local tissue structures
-no propensity for distant spread |
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malignant tumor
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invasion of local or distant tissue structures
-distant spread will or has occurred |
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cancer definition
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-disease of abnormal cells exhibiting:
-uncontrolled cell growth -decreased cell differentiation -inappropriate invasion of surrounding tissue -ability to establish new growth at ectopic sites -it is NOT a cell that grows too fast |
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stages of carcinogenesis
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-initiation
-promotion -transformation -progression |
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initiation stage of carcinogenesis
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-exposure of normal cells to carcinogen
-activate proto-oncogenes -inactivate tumor suppressor genes -genetic damage- cellular mutation |
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promotion stage of carcinogenesis
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-carcinogens alter environment
-favor growth of mutated cells -defects in growth and differentiation -reversible process! |
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transformation stage of carcinogenesis
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-conversion
-mutated cell becomes cancerous -takes a longer time (2-20 yrs) |
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progression stage of carcinogenesis
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-further genetic changes
-tumor invasion into local structures- malignant -metastasis |
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warning mnemonic for cancer sxs in children
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CHILDREN
-weight loss, HA, swelling, lump, white pupils, fevers, bruising/bleeding, paleness |
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warning mnemonic for cancer sxs in adults
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CAUTION
-change in bladder/bowel, sores, bleed/discharge, lump, indigestion, wart/mole, cough/hoarseness |
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staging of cancer based on 3 items
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tumor (size)
nodes metastasis (TNM staging) |
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complete response
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complete disappearance of signs/symptoms of cancer >1 month
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partial response
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>50% reduction in tumor burden, and no new lesions for >1 month
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stable disease
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tumor burden not increasing or decreasing by >25% for >1 month
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progressive disease
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>25% increase in tumor burden or development of new lesions
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skipper and schabel cell kill hypothesis
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particular dose of chemo will kill constant proportion of cells (independent of size of tumor)
-best explains activity of high-dose chemo |
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norton and simon cell kill hypothesis
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maximal cell kill occurs at times of maximal tumor growth
-use dose-dense or metronomic chemo |
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induction chemo
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drug therapy as primary treatment
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salvage chemo
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drug therapy used after primary treatment fails
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adjuvant chemo
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drug therapy employed after treatment with another method (surgery or radiation)
-to kill residual and circulating tumor cells |
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neo-adjuvant chemo
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use of chemo prior to another modality (radiation or surgery)
-allows for greater surgical efficacy -reduce tumor size, intact vasculature |
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single agent chemo limited to following settings:
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-regional therapy
-high dose regimens -malignancies w/out known effective combos -salvage -palliation |
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goldie-coleman hypothesis for combination chemo theory
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-max chance for cure when all effective agents given simultaneously
-use 2 alternating regmiens of non-cross resistant chemo combos |
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day hypothesis for combo chemo therapy
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-sequential use of combos better than alternating
-proposed "worst drug rule" - using more or earlier doses of tx shown least effective |
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intent of chemo- induction
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high dose combo therapy
-intent to get complete remission |
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intent of chemo- consolidation
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-chemo given after a remission obtained
-intent to increase the cure rate or prolong remission |
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intent of chemo- maintenance
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chemo at lower doses with goal of prolonging remission
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intent of chemo- palliative
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improve quality of life or to prolong life in patients where cure unlikely
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intent of chemo- salvage
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potentially curative regimen for patients that failed or recurred after a first line curative regimen
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MOA of alkylating agents
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contribution of an alkyl group (positively charged group, electrophilic drug) into an organic compound (negative charged target molecule, nucleophilic, N-7 of guanine on DNA), causes single/double strand breaks in DNA (inhibits DNA transcription/replication), cause misreading/mispairing, # of intrastrand cross-links directly correlates w/ cytotoxic response
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mechlorethamine
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alkylating agent- nitrogen mustard
used today d/t toxicites (N, V, infertility) |
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cyclophosphamide
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alkylating agent- nitrogen mustard
most used alkylating agent – IV and oral -used in breast cancer, liquid tumors, prep for bone marrow transplant -prodrug (hydrolyzed to phosphoramide mustard and acrolein) -ADEs: DLT is myelosuppression (neutropenia), alopecia, N/V (can be delayed), SIADH, hemorrhagic cystitis (d/t acrolein – prevent with mesna, hydration, and voiding of urine |
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ifosfamide
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alkylating agent- nitrogen mustard
analogue of cyclophosphamide -must be used with mesna IV or oral -ADEs: hemorrhagic cystitis guaranteed, N/V (can be delayed) |
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melphalan
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alkylating agent- nitrogen mustard
IV or oral -used in multiple myeloma, lymphomas -take on empty stomach |
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chlorambucil
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alkylating agent- nitrogen mustard
oral -used in CLL -take on empty stomach |
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dacarbazine
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alkylating agent- triazeneIV
-prodrug activated by P450 -poorly lipid soluble -ADEs: delayed leukopenia/thrombocytopenia (25 days), severe N/V (>90%) |
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temozolomide
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alkylating agent- triazene
oral -degraded to active drug at physiological pH -crosses BBB (more lipid soluble than IV equivalent dacarbazine) -give on empty stomach -ADEs: GI toxicity, myelosuppression with certain regimen, PJP pneumonia |
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carmustine
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alkylating agnet- nitrosourea
IV -highly lipophilic, crosses BBB -for brain tumors -ADEs: delayed myelosuppression (4 weeks) -given only as single dose once every 6 weeks |
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lomustine
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alkylating agnet- nitrosourea
– PO -highly lipophilic, crosses BBB -for brain tumors -take on empty stomach -ADEs: delayed myelosuppression (4 weeks) -given only as single dose once every 6 weeks |
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bendamustine
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alkylating agnet- nitrosourea
– IV -novel alkylator/purine analog -approved for CLL (chronic lymphocytic lymphoma) and refractory indolent NHL (non-hodkin’s lymphoma) -ADEs: like other alkylating agents (myelosuppression, alopecia, N, V) |
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cisplatin
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alkylating agent- platinum
-used in bladder, testicular, ovarian, lung, cervical, head, neck cancers -high ADEs (worse than carboplatin) -ADEs: acute DLT is renal toxicity, chronic DLT is neurotoxicity, myelosuppression, N, V (both acute and delayed), e-lyte disturbances (K and Mg wasting), Scr peaks -acute renal toxicity: extensive damage to proximal/distal tubules (Cl protects) -management: pre-hydrate with NS + Mg/K, goal UO > 100ml/hr, reduce dose with renal dysfunction |
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carboplatin
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alkylating agent- platinum
-dose with AUC -slower activation d/t increased stabililty (but similar amt of DNA crosslinks) -used in bladder, testicular, ovarian, lung, cervical, head, neck cancers -less ADEs than cisplatin -ADEs: DLT is myelosuppression (thrombocytopenia), N, V (both acute and delayed), electrolyte disturbances |
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oxaliplatin
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alkylating agent- platinum
-used in colorectal and pancreatic cancer -ADEs: peripheral neuropathy (acute and cumulative sensory exacerbated by cold) -acute: minutes/hours/1-2 days after infusion (can be severe/life-threatening) -chronic: is DLT – has a high incidence, is expected, dose/duration dependent, S/S include paresthesias, dysthesias, abnormalities in propioception |
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procarbazine
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alkylating agent- other
-s phase cell cycle specific |
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MOA of anthracyclines
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S phase cell cycle specific
-MOA: intercalate into DNA, interfere with topo II, break strand, form ROS, requires Fe (cause of cardiotoxicity) -indications: breast, ovarian, bladder, hematologic -ADEs: -DLT is myelosuppression (leukopenia) -N/V, alopecia, potent vesicants (cause necrosis in tissues if leaves blood vessels) -chronic DLT is cardiac toxicity (with cumulative dose – requires baseline cardiac test), -anthracycline extraavasation in 1% of patients (less risk with central catheter – treat with dexrazoxane which chelates free radical iron) |
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anthracycline drugs
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(topo II inhibitors)
-Daunorubicin -Doxorubicin -can have delayed N/V -Epirubicin -Idarubicin |
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mitoxantrone
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anthracycline analogue
-topo ll inhibitor G2 phase cell cycle specific -indications: hematologic malignancies, prostate cancer -analog to anthracyclines -lacks formation of free radicals (reduced activity and toxicity) -ADEs: DLT is myelosuppression (leukopenia), N/V, alopecia, cardiac toxicity (chronic DLT) |
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etoposide
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epipodophyllotoxin (topo II inhibitor)
M phase cell cycle specific -MOA is single strand DNA breaks d/t complexs with topo II -used for SCLC, testicular, lymphomas -IV or oral (refrigerate) -ADEs: DLT is myelosuppression (leukopenia), N/V, alopecia |
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topotecan
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camptothecin- topo I inhibitor
G2 phase cell cycle specific -MOA is inhibition of topo I cuasing stabilization of cleavable complexes, SS DNA breaksoral or IV -used for SCLC and ovarian -ADEs: DLT myelosuppression (leukopenia/thrombocytopenia) |
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irinotecan
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camptothecin- topo I inhibitor
G2 phase cell cycle specific -MOA is inhibition of topo I cuasing stabilization of cleavable complexes, SS DNA breaks -used for colorectal cancer -ADEs: DLT is diarrhea (both acute and delayed) -acute: cholinergic related – use atropine -delayed: d/t metabolite SN-38 – use loperamide |
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vincristine
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antimicrotubule- vinca alkaloid
-m phase specific -MOA: bind to tubulin, prevent microtubule formation-used for hematologic malignancies -ADEs: DLT is neurotoxicity (depression of deep tendon reflex and motor) and constipation (not usually myelosuppressive) -dose capped at 2mg -fatal if given intrathecally |
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vinblastine
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antimicrotubule- vinca alkaloid
-m phase specific -MOA: bind to tubulin, prevent microtubule formation -used for solid/hematologic malignancies -ADEs: DLT is myelosuppression (leukopenia, thrombocytopenia), C, neurologic toxicity (d/t binding of tubulin in nerves), fatal if given intrathecally |
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vinorelbine
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antimicrotubule- vinca alkaloid
-m phase specific -MOA: bind to tubulin, prevent microtubule formation -used for solid/hematologic malignancies -ADEs: DLT is myelosuppression (leukopenia, thrombocytopenia), C, neurologic toxicity (d/t binding of tubulin in nerves), fatal if given intrathecally |
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vindesine
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antimicrotubule- vinca alkaloid
-m phase specific -MOA: bind to tubulin, prevent microtubule formation -fatal if given intrathecally |
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paclitaxel
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antimicrotubule- taxanes
-m phase specific -MOA: promotes microtubule assembly and stabilization against depolarization (can’t change cell cycles) -used in breast, ovarian, prostate, lung -ADEs: DLT is myelosuppression (leukopenia) with 3 hour infusion, DLT is peripheral neuropathy with 24 hour infusion, alopecia, mucositis -formulated in cremophor -hypersensitivity reactions (SOB and hypotension) |
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doxcetaxel
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antimicrotubule- taxanes
-m phase specific -MOA: promotes microtubule assembly and stabilization against depolarization (can’t change cell cycles) -used in breast, ovarian, prostate, lung -ADEs: DLT is myelosuppression (leukopenia) with 3 hour infusion, DLT is peripheral neuropathy with 24 hour infusion, alopecia, mucositis -formulated in polysorbate 80 and ethanol -less hypersensitivity than paclitaxel |
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nab-pacitaxel
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antimicrotubule- taxanes
-m phase specific -MOA: promotes microtubule assembly and stabilization against depolarization (can’t change cell cycles) -used in breast, ovarian, prostate, lung -ADEs: DLT is myelosuppression (leukopenia) with 3 hour infusion, DLT is peripheral neuropathy with 24 hour infusion, alopecia, mucositis -albumin bound paclitaxel – free of solvents -less ADEs than paclitaxel and doxcetaxel -additional antitumor efficacy seen |
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ixabepilone
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antimicrotubule- epothilone
-MOA targets tubulin (manipulates tubulin binding pocket differently than taxanes) -used for breast cancer -formulated in cremophor (like paclitaxel) |
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antimetabolite general MOA
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S phase cell cycle specific??
-general MOA: structural similarity to molecules involved in DNA synthesis, inhibits necessary enzymes, incorporated into nucleic acid, inhibits DNA synthesis causing cell death (doesn’t just kill enzymes in tumor cells – kills healthy cells as well) |
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methotrexate
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antimetabolite- folic acid analogue
IV, IT, PO -MOA is inhibition of DHFR leading to depletion of reduced folates (tetrahydrofolate is required in providing single carbon groups for the synthesis of precursors of DNA/RNA) -used in breast, leukemia, lymphoma, sarcomas, and more -ADEs: DLT is myelosuppression (leukopenia/thrombocytopenia), mucositis, alopecia, N/V/D, pulmonary pneumonitis -high dose MTX is lethal without leucovorin rescue (if dose >500mg/m2) b/c high dose MTX can cause renal tubular necrosis (requires hydration, alkalinization) -drug interactions: NSAIDs, PCN, fluoroquinolones (compete with renal excretion), vitamin C acidifies urine (decreases excretion), highly protein bound drugs can displace MTX (phenytoin, salicylates, sulfonamides, tetracycline) |
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pemetrexed
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antimetabolite- folic acid analogue
-MOA: broader than MTX (inhibits DHFR and thymidylate synthesis (TS) and GARFT -ADEs: DLT is neutropenia, mucositis, alopecia, N/V/D, pulmonary pneumonitis -requires vitamin B12 and folic acid supplementation (reduces mucositis risk) |
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cytarabine
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antimetabolite- pyrimidine analogue
-MOA: structural analogues of cytidine and deoxycytidine – competes with DNA polymerase, stops DNA chain elongation, incorporates into DNA or RNA -used in leukemias -ADEs: DLT is myelosuppression (leukopenia/thrombocytopenia), N/V/D, mucositis -conjunctivitis and cerebellar toxicity with high doses |
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gemcitabine
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antimetabolite- pyrimidine analogue
-MOA: structural analogues of cytidine and deoxycytidine – competes with DNA polymerase, stops DNA chain elongation, incorporates into DNA or RNA -activated intracellularly -used in pancreatic, lung, breast, bladder, ovarian -ADEs: DLT is myelosuppression (leukopenia/thrombocytopenia), N/V/D, mucositis |
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fluorouracil
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antimetabolite- pyrimidine analogue
IV continuous infusion or bolus -MOA: inhibits formation of thymidine, inhibits enzyme thymidylate synthase (TS) which is the RLS in thymidine synthesis -used in colorectal, breast, liver, head/neck, stomach cancer -ADEs: -bolus: DLT is myelosuppression (leukopenia, thrombocytopenia and anemia), other is diarrhea, mucositis -continuous: DLT is hand-foot syndrome and diarrhea, other is myelosuppression |
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capecitabine
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antimetabolite- pyrimidine analogue
-oral produg to 5-FU (activated intracellularly) -thymidine phyosphorylase levels are higher in tumor cells than normal cells -ADEs: DLT is hand-foot syndrome and diarrhea, other is myelosuppression |
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azacytidine
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antimetabolite- pyrimidine analogue
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decitabine
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antimetabolite- pyrimidine analogue
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tamoxifen
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hormonal agent-MOA: inhibition of nuclear binding of the estrogen receptor on breast cancer cells
-estrogen antag in breast cancer, estrogen agonist in endometrium and bone (SERM) -converted to active drug by CYP2D6 (make sure pt not on 2D6 inhibitor) -used for pre/postmenopausal women with ER+ breast cancer, prophylaxis in women at high risk for breast cancer (given for 5 years) -serious risks: thromboembolic events, endometrial cancer -ADEs: hot flashes, fluid retention, vaginal bleeding (induce menopause) -drug interactions: inhibitors of 2D6, SSRIs (paxil>prozac>Zoloft>>effexor) |
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raloxifene
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hormonal agent-SERM
-used for prophylaxis of breast cancer in high risk women -similar efficacy as tamoxifen, but lower ADEs (thromboembolic and cataracts), but more expensive |
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anastrozole
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hormone agent- aromatase inhibitor
-MOA: decrease peripheral production of estrogens -used only in postmenopausal women with ER+ breast cancer (does not interfere w/ ovarian estrogen production) -ADEs: weakness, bone pain, hot flashes, edema -calcium and vitamin D replacement recommended, and bisphosphonates |
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letrozole
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hormone agent- aromatase inhibitor
-MOA: decrease peripheral production of estrogens -used only in postmenopausal women with ER+ breast cancer (does not interfere w/ ovarian estrogen production) -ADEs: weakness, bone pain, hot flashes, edema -calcium and vitamin D replacement recommended, and bisphosphonates |
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exemestane
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hormone agent- aromatase inhibitor
-MOA: decrease peripheral production of estrogens -used only in postmenopausal women with ER+ breast cancer (does not interfere w/ ovarian estrogen production) -ADEs: weakness, bone pain, hot flashes, edema -calcium and vitamin D replacement recommended, and bisphosphonates |
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finasteride
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hormone agent- 5 alpha reductase inhibitor
-MOA: blocks conversion of testosterone to DHT -used for prostate cancer prevention (25% reduction) -but increase in high-grade tumors, and high cost -ADEs: decreased libido, sexual dysfxn, gynecomastia |
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dutasteride
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hormone agent- 5 alpha reductase inhibitor
-MOA: blocks conversion of testosterone to DHT -used for prostate cancer prevention (25% reduction) -but increase in high-grade tumors, and high cost -ADEs: decreased libido, sexual dysfxn, gynecomastia |
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goserelin
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hormone agent- LHRH agonist
-MOA: constant stimulation of pituitary leading to down-regulation of LH production (testosterone deprivation) |
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leuprolide
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hormone agent- LHRH agonist
-MOA: constant stimulation of pituitary leading to down-regulation of LH production (testosterone deprivation) |
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abarelix
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hormone agent- LHRH antag
-MOA: constant stimulation of pituitary leading to down-regulation of LH production (testosterone deprivation) -synthetic antag of LHRH -causes immediate testosterone depletion |
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thalidomide
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newer oral agent
--in past when used caused fetal abnormalities -MOA: unknown (immunomodulation, anti-inflammatory, anti-proliferative, and anti-angiogenic properties) -used in hematologic malignancies -ADEs: VTEs/PEs (higher risk with dexamethasone and chemo), teratogenic, peripheral neuropathy -STEPS program |
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lenalidomide
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newer oral agent
-derivative of thalidomide -MOA: stronger anti-inflammatory and anti-angiogenic properties -ADEs: VTEs/PEs (higher risk with dexamethasone and chemo), teratogenic, myelosuppression (neutropenia/thrombocytopenia), no neuropathy (unlike thalidomide) -Revassist program |
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gefitinib
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tyrosine kinase inhibitor - EGFR inhibitor
-only allowed now for patients that previously showed benefit after disappointing trials |
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erlotinib
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tyrosine kinase inhibitor - EGFR inhibitor-MOA: competes with ATP binding site of EGFR receptor, inhibits autophosphorylation
-used in NSCLC and pancreatic -take on empty stomach -ADEs: acne-like rash, dry skin, N/V/D, fatigue -drug interactions: major substrate of CYP3A4 |
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imatinib
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tyrosine kinase inhibitor - BCR-ABL inhibitor
-MOA: inhibits BCR-ABL tyrosine kinase, c-KIT -used in CML and GIST (GI stromal tumor) -take with food and water -ADEs: N/V/D, ab pain, rash, fluid retention, muscle cramp, e-lyte (low PO4, Mg, and Ca) -drug interactions: major substrate of CYP3A4 |
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nilotinib
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tyrosine kinase inhibitor - BCR-ABL inhibitor-MOA: inhibits BCR-ABL tyrosine kinase and mutants (works on imatinib resistant)
-used in intolerant CML or imatinib-resistant cases -take on empty stomach -ADEs: rash, N, pruritis, HA, fatigue -drug interactions: major substrate of CYP3A4 |
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dasatinib
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tyrosine kinase inhibitor - BCR-ABL inhibitor
-MOA: inhibits BCR-ABL tyrosine kinase and mutants (works on imatinib resistant), and Src family of kinases -used in imatinib-resistant cases, intolerant CML -take with or without food -ADEs: N/V/D, ab pain, rash, fluid retention, muscle cramps -drug interactions: major substrate of CYP3A4 |
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sorafenib
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multi-targeted tyrosine kinase inhibitor
-MOA: targets RAF kinase (MAPK pathway) + other tyrosine kinases involved in tumor cell proliferation and angiogenesis -used in hepatocellular carcinoma and advanced renal cell carcinoma -dose on empty stomach -ADEs: diarrhea, rash, fatigue, alopecia, hand-foot syndrome or PPE |
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sunitinib
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multi-targeted tyrosine kinase inhibitor
-MOA: inhibits multiple tyrosine kinases (VEGFR, PDGFR, c-KIT) -used in GIST (GI stromal tumor) and RCC (renal cell carcinoma) -ADEs: HTN, decreased left ventricular ejection fraction, fatigue, skin changes, QT interval prolongation -drug interactions: primarily metabolized by CYP3A4 |
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lapatinib
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HER-2 inhibitor - tyrosine kinase inhibitor
oral (unlike trastuzumab) -used for HER2+ metastatic breast cancer -take on empty stomach (fatty food increases concentration) -crosses BBB (unlike trastuzumab) -ADEs: diarrhea, rash, possible cardiotoxicity -drug interactions: CYP3A4 metabolized (fluconazole increases conc, carbamazepine decreases conc) – trastuzumab does not have DIs -very expensive |
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rituximab
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monoclonal antibody - CD20 binder
-unconjugated monoclonal antibodies: activate host defense system, complement-mediated cytotoxicity, apoptosis -used in non-hodgkin’s lymphoma (CD20 antigen in >95% of B-cell NHL) -ADEs: high frequency with first infusion (hypotension, SOB) -pretreatment prevention medications (Tylenol, Benadryl, steroids) |
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ibritumomab-tiuxetan
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monoclonal antibody - CD20 binder-radioactive immunotherapy: antibodies are vehicles, radioactive isotopes deliver cytotoxic effects (radioactive yttrium-90)
-given after rituximab for NHL, or for low grade NHL (if radiosensitive) -ADEs: delayed, long-lasting hematologic toxicity (months) -require patient instruction to decrease exposure to others |
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tositumomab-iodine
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monoclonal antibody - CD20 binder
-radioactive immunotherapy: antibodies are vehicles, radioactive isotopes deliver cytotoxic effects -given in relapsed or refractory CD20+ follicular NHL -ADEs: delayed, long-lasting hematologic toxicity (>3 months) -require patient instruction to decrease exposure to others |
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gemtuxumab-ozogamicin
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monoclonal antibody - CD33 binder
-drug conjugates: preferential delivery of cytotoxic drug to tumor (linked with calicheamycin – potent cytotoxic antibiotic) -MOA: released intracellularly to cause DS DNA breaks -used in AML and MDS (myelodysplastic syndrome), in patients >60 that cannot tolerate cytotoxic therapy |
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alemtuzumab
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monoclonal antibody - CD52 binder
-used for patients with B-CLL (B cell chronic lymphocytic leukemia) -ADEs: opportunistic infections (d/t low CD4 count) -require PCP and herpes prophylaxis during and 3 months after treatment |
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trastuzumab
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monoclonal antibody - HER2 binder
IV (unlike lapatinib) -MOA: binds to extracellular domain of HER2 to prevent dimerization (HER2 overexpression associated with uncontrolled growth, aggressive cancer) -used in breast cancer (HER2+ patients 20-30%) -ADEs: minimal except for cardiotoxicity (reversible after withdrawal unlike anthracyclines) -does not cross BBB (unlike lapatinib) -lacks drug interactions (unlike lapatinib) |
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cetuximab
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monoclonal antibody - HER1 binder
-MOA: binds to epidermal growth factor / HER1 -chimeric IgG1 monoclonal antibody (MoAb) -used for colorectal cancer, squamous cell cancer of head/neck -ADEs: follicular rash, hypomag, fatigue, N/V/D |
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panitumumab
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monoclonal antibody - HER1 binder
-MOA: binds to EGFR/HER1 -fully humanized IgG2 monoclonal antibody (MoAb) -lack of antibody-dependent cell-mediated cytotoxicity -used for colorectal cancer -ADEs: follicular rash, hypomag, fatigue, N/V/D |
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bevacizumab
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monoclonal antibody- VEGF binder
-MOA: targets vascular endothelial growth factor receptor (VEGF associated with angiogenesis) -used in patients with metastatic colorectal cancer, NSCLC, metastatic breast cancer -ADEs: HTN (d/t decreased NO production) in 30% of patients, impaired wound healing (d/t reduced angiogenesis), risk of thromboembolism, proteinuria (20%) -contraindicated 28 days after surgery, stopped before elective surgery |
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types of CINV- acute
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vomiting occurring within 24 hrs, peaks 4-6 hrs after chemo, involves 5-HT and DA
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types of CINV- delayed
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24hrs-5days, peak 48-72 hrs, involves neurotransmitters other than 5-HT, more likely to cause anticipatory N/V
-drugs that cause delayed: cisplatin, carboplatin, doxorubicin, ifosfmide, cyclophosphamide |
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types of CINV- anticipatory
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triggered by sight, sound, smell, not associated with neurotransmitters
-d/t inadequate control of N/V in past, occurs before chemo |
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types of CINV- breakthrough
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emesis on day of chemo despite appropriate antiemetic regimen
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cortical pathway
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anticipatory (triggers are anxiety and sensory input)
-prevention: adequate prior CINV control -treatment: -benzodiazepenes- ativan -H1 receptor antagonists- hydroxyzine, diphenhydramine |
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vestibular pathway
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motion-associated (triggered by chemo or fluids/e-lyte disturbance)
-muscarinic acetylcholine pathway -prevention: N/A -treatment: -anticholinergic agents- scopolamine patch, phenothiazines (phenergan) |
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GI afferent pathway
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-stomach and SI – EC cells release 5-HT and NK-1 in response to toxin (chemo)
-can either directly stimulate medulla or stimulate CTZ zone -prevention: 5-HT and NK-1 antagonists -treatment: 5-HT and NK-1 antagonists -serotonin antagonists (5HT3)- ondansetron, granisetron, dolasetron, palonosetron -neurokinin-1 antagonists- aprepitant -high dose metoclopramide (low dose just gets DA, high dose gets 5-HT too) |
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CTZ
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-has permeable BBB – signals medulla to coordinate vomiting reflex in response to toxin
-can be independently stimulated (by 5-HT, DA, NK-1, muscarinic, H1-histamine) or stimulated by GI (enterochromaffin cells) -prevention: 5-HT, DA and NK-1 antagonists -treatment: 5-HT, DA and NK-1 antagonists -serotonin antagonists (5HT3)- ondansetron, granisetron, dolasetron, palonosetron -neurokinin-1 antagonists- aprepitant -high dose metoclopramide |
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risk factors for CINV
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-increasing risk: prior chemo, poor prior N/V control, depression, motion sickness, children>adults, women>men
-decreasing risk: heavy prior alcohol use, marijuana use |
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dolasetron
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CINV
-serotonin antagonists: (best for acute, delayed with palonestron only) -all metabolized by CYP3A4 -ADEs: HA, C, ECG abnormalities -all agents have similar efficacy when equipotent doses used -**little efficacy > 24 hours after last dose of chemo (give with adjunctive agent- glucocorticoid- inc. effect by 20%, benzo, DA antag) -used for moderate-highly emetogenic chemo -only antiemetic class with minimal sedation |
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granisetron
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CINV
-serotonin antagonists: (best for acute, delayed with palonestron only) -all metabolized by CYP3A4 -ADEs: HA, C, ECG abnormalities -all agents have similar efficacy when equipotent doses used -**little efficacy > 24 hours after last dose of chemo (give with adjunctive agent- glucocorticoid- inc. effect by 20%, benzo, DA antag) -used for moderate-highly emetogenic chemo -only antiemetic class with minimal sedation -most selective for 5HT-3 -transdermal patch |
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ondansetron
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CINV
-serotonin antagonists: (best for acute, delayed with palonestron only) -all metabolized by CYP3A4 -ADEs: HA, C, ECG abnormalities -all agents have similar efficacy when equipotent doses used -**little efficacy > 24 hours after last dose of chemo (give with adjunctive agent- glucocorticoid- inc. effect by 20%, benzo, DA antag) -used for moderate-highly emetogenic chemo -only antiemetic class with minimal sedation -has generic |
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palonosetron
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CINV
-serotonin antagonists: (best for acute, delayed with palonestron only) -all metabolized by CYP3A4 -ADEs: HA, C, ECG abnormalities -all agents have similar efficacy when equipotent doses used -**little efficacy > 24 hours after last dose of chemo (give with adjunctive agent- glucocorticoid- inc. effect by 20%, benzo, DA antag) -used for moderate-highly emetogenic chemo -only antiemetic class with minimal sedation -long t1/2 -only 5-HT agent for acute and delayed (rest just acute) -only need 1 dose per 5 days of chemo (started day 1 before delayed N/V starts) |
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aprepitant
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oral for CINV-neurokinin-1 antagonists: (best for acute and delayed prevention- started before onset)
-use with other antiemetics for prevention of acute and delayed CINV (not treatment) -use with all highly emetogenic chemo, some moderately emetogenic (platinoids, doxorubicin, ifosfamide, irinotecan) -drug interactions: NK-1 antags are 3A4 inhibitors (caution with 3A4 substrates like ifosfamide or irinotecan) -must reduce dexamethasone dose 40% |
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fosaprepitant
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IV for CINV
-neurokinin-1 antagonists: (best for acute and delayed prevention- started before onset) -use with other antiemetics for prevention of acute and delayed CINV (not treatment) -use with all highly emetogenic chemo, some moderately emetogenic (platinoids, doxorubicin, ifosfamide, irinotecan) -drug interactions: NK-1 antags are 3A4 inhibitors (caution with 3A4 substrates like ifosfamide or irinotecan) -must reduce dexamethasone dose 40% |
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dexamethasone
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CINV
-glucocorticoids (best for acute and delayed) -MOA unknown -effective for acute and delayed CINV for all ematogenicity levels -limited role as single agent (better in combo- synergy with 5-HT and DA antags) -benefits outweigh risks (routinely used as premed) -ADEs limit long term use |
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alprazolam
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CINV
-benzodiazepines (best for anticipatory, and acute and breatkthrough) -MOA: anterograde amnesia -prevents anticipatory CINV -used in combo as premed for acute or single-agent as breakthrough -little role in delayed -ADEs: sedation and altered mental status -only anxiolytic benzos are useful |
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lorazepam
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CINV-benzodiazepines (best for anticipatory, and acute and breatkthrough)
-MOA: anterograde amnesia -prevents anticipatory CINV -used in combo as premed for acute or single-agent as breakthrough -little role in delayed -ADEs: sedation and altered mental status -only anxiolytic benzos are useful |
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diazepam
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CINV
-benzodiazepines (best for anticipatory, and acute and breatkthrough) -MOA: anterograde amnesia -prevents anticipatory CINV -used in combo as premed for acute or single-agent as breakthrough -little role in delayed -ADEs: sedation and altered mental status -only anxiolytic benzos are useful |
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metoclopramide
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CINV
-benzamide analogs (best for acute or delayed) -drug of choice prior to serotonin antagonists -MOA: block DA in CTZ, increase gut motility, block peripheral 5-HT -must use anticholingic with high dose metoclopramide |
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trimethobenzamide
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CINV
-benzamide analogs (best for acute or delayed) |
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prochlorperazine
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CINV
-phenothiazine derivatives (best for delayed or breakthrough) -MOA: blocks DA receptors in CTZ -only for low or moderate emetogenicity -used in delayed and breakthrough CINV (limited use for acute) -ADEs: sedation limits use -class of drugs with most flexible routes (PO, IV, IM, PR) |
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promethazine
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CINV
-phenothiazine derivatives (best for delayed or breakthrough) -MOA: blocks DA receptors in CTZ -only for low or moderate emetogenicity -used in delayed and breakthrough CINV (limited use for acute) -ADEs: sedation limits use -class of drugs with most flexible routes (PO, IV, IM, PR) -IV form is a vesicant (can cause tissue necrosis) |
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haloperidol
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CINV
-butyrophenones (best for acute, delayed, or breakthrough) -MOA: blocks dopamine receptors in CTZ -more selective and effective than phenothiazines (active in phenothiazine failure) -effective for acute and delayed CINV with all emetogenicity levels -ADEs: less sedating than other DA antagonists, but associated with tachyarrhythmia |
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droperidol
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CINV
-butyrophenones (best for acute, delayed, or breakthrough) -MOA: blocks dopamine receptors in CTZ -more selective and effective than phenothiazines (active in phenothiazine failure) -effective for acute and delayed CINV with all emetogenicity levels -ADEs: less sedating than other DA antagonists, but associated with tachyarrhythmia -black box warning for cardiac arrhythmias |
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dronabinol
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CINV
-cannabinoids (best for acute or breakthrough) -used for low and moderate emetogenicity -ADEs: limit use (dysphoria, ataxia, dizziness, hypotension) -marijuana users get most benefit b/c less affected by ADEs -tolerance to side effects develops in time |
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nabilone
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CINV
-cannabinoids (best for acute or breakthrough) -used for low and moderate emetogenicity -ADEs: limit use (dysphoria, ataxia, dizziness, hypotension) -marijuana users get most benefit b/c less affected by ADEs -tolerance to side effects develops in time |
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scopolamine
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CINV- anticholinergic
-motion associated (vestibular) -miscellaneous antiemetic |
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diphenhydramine
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CINV- anticholinergic
-motion associated (vestibular) -miscellaneous antiemetic |
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olanzapine
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refractory CINV
-atypical antipsychotic |
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highly emetogenic regimen
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-premed for acute: aprepitant + 5-HT antag + glucocorticoid + benzo
-delayed: DA antag + glucocorticoid +/- benzo -breakthrough: benzo + DA antag |
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moderately emetogenic regimen
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premed for acute: 5-HT antag + glucocorticoid + benzo
-delayed: DA antag + glucocorticoid -breakthrough: benzo + DA antag |
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low emetogenic regimen
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-premed for acute: DA antag
-delayed: N/A -breakthrough: DA antag |
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minimal emetogenic regimen
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no routine antiemetic recommended, if proven CINV, consider benzo
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radiation induced N/V regimen
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5-HT antag + glucocorticoid
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