Term
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Definition
Class: Antimetabolite
Mechanism of Action: 1) Analog of uracil; metabolized to FdUMP, which interferes with thymidylate synthase activity, preventing thymidine formation. 2) Triphosphate metabolite gets incorporated into RNA and disrupts RNA synthesis.
Uses: Colon, anus/rectum, gastric, pancreatic, esophageal, head and neck, and breast cancer
Side effects:
Stomatitis (also esophagitis and gastric ulcers), Arrhythmia (rare)
Alopecia
Book: diarrhea, neurotoxicity (headache, visual disturbance, cerebellar ataxia) |
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Term
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Definition
Class: Antimetabolite
Mechansim: 5-FU prodrug; 5-FU can inhibit thymidylate synthase and be incorporated into RNA (see 5-FU card)
Uses:
Metastatic breast cancer
Metastatic colorectal cancer
Side effects:
Stomatitis (mucositis)
Palmar-plantar erythrodysthesia (hand-foot syndrome)
Book: Diarrhea, myelosuppression, nausea; increased activity of warfarin and phenytoin |
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Term
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Definition
Class: Antimetabolite
Mechanism: Cytosine analog; triphosphate form 1) inhibits DNA polymerase and 2) may be incorporated into DNA, resulting in chain termination
Uses:
Book: Acute leukemias and some lymphomas
Side effects:
Hepatotoxicity--veno-occlusive disease
Cerebellar toxicity (nystagmus, dysarthria, and ataxia)
Book: Myelosuppression, eye irritation (need steroid eyedrops constantly) |
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Term
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Definition
Class: Antimetabolite (pyrimidine analog)
Mechanism: Deoxycytidine analog (similar to cytarabine); Inhibits DNA polymerase and ribonucleotide reductase
Uses:
Pancreatic cancer
Non-small cell lung cancer (combo with cisplatin)
Metastic breast cancer (combo with paclitaxel), after failure with anthracycline abx
Ovarian cancer (combo with carboplatin), after relapse following platinum-based tx
Side effects:
Book: Myelosuppression, flu-like syndrome, fever (first 24 h: can use APAP, 7-10 days later: likely infection), rash (48-72 hours post admin), hemolytic uremic syndrome (life-threatening) |
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Term
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Definition
Class: Purine/Purine Antimetabolite
Mechanism: Adenine analog; interferes with DNA polymerase; incorporated into RNA to inhibit transcription
Uses:
CLL
Book: some lymphomas, and refractory AML
Side effects:
Pulmonary toxicity (book: interstitial pneumonitis)
Book: Significant myelosuppression and immunosuppression, mild n/v/d |
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Term
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Definition
Class: Antifolate
Mechanism: Inhibits dihydrofolate reductase, thereby blocking folates from being transported into the cell for thymidylate and purine synthesis
Uses:
Book: Lymphomas, ALL; gastric, esophageal, bladder, and breast cancer
Side effects:
Renal toxicity; must give bicarbonate to increase urine pH and prevent methotrexate crystallization
Mucositis
Pulmonary toxicity
Alopecia
Book: Myelosuppression, n/v; interacts with with drugs that compete for tubular secretion |
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Term
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Definition
Class: Antifolate (antimetabolite)
Mechanism: Inhibits at least 3 pathways in thymidine and purine synthesis
1. Dihydrofolate reductase
2. Thymidylate synthase
3. GARFT
Uses:
Mesothelioma
Nonsmall cell lung cancer
Side effects:
Book: myelosuppression, rash (avoid by giving dexamethasone), diarrhea and bone marrow toxicity (avoid by giving folic acid and cyanocobalamin), n/v |
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Term
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Definition
Class: Vinca alkaloid
Mechanism: Arrests cells in metaphase
Uses:
Lymphomas
ALL (used in a 3-drug combo with a high cure rate)
Side effects:
DOSE LIMITING = neuropathy!! (May cap dose at 2 mg)
vesicant (neuropathy, blisters), ileus, constipation; neurogenic bladder, absence of deep reflexes, and paralysis of lower extremities when co-administered with itraconazole |
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Term
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Definition
Class: Vinca alkaloid
Mechanism: inhibits assembly of microtubules to arrest cells in metaphase
Uses:
Hodgkin's lymphoma
Ovarian, breast, nonsmall cell lung, prostate, esophageal, gastric and head and neck cancers
Side effects:
Alopecia
Less neurotoxicity compared to vincristine
Book: rash, photosensitivity, stomatitis |
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Term
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Definition
Class: Taxane
Mechanism: Binds to tubulin to promote microtubule assembly and prevent disassembly
Uses:
Widely used! Breast, ovarian, lung cancer...
Side effects:
Peripheral neuropathy
Alopecia
Book: Dexamethasone, diphenhydramine, and H2 blocker given to prevent hypersensitivity; asymptomatic bradycardia; myalgia/arthralgia 3-5 days after; myelosuppression; flushing; neuropathy; ileus; total-body alopecia; must be given before cisplatin; clearance increased when given with phenytoin
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Term
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Definition
Class: Tubulin active agent
Mechanism: Binds to β-tubulin subunit, which suppresses microtubule dynamics; has activity in taxane-resistant cell lines
Use:
2nd line for breast cancer (use after failure with anthracycline, taxane, and capecitabine)
Side effects:
Book: Hypersensitivity (give H1 and H2 blockers beforehand to avoid--and corticosteroid if needed); myelosuppresion; peripheral neuropathy |
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Term
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Definition
Class: Topoisomerase inhibitor
Mechanism: Inhibits topoisomerase I and II, causing multiple double strand and single strand DNA breaks
Uses:
Book: Several lymphomas; testicular and lung cancer; retinoblastoma; carcinoma
Side effects:
Secondary neoplasm
Alopecia
Book: mucositis, myelosuppression,phlebitis, hypersensitivity; must give slowly to prevent hypotension |
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Term
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Definition
Class: Topoisomerase inhibitor
Mechanism: Inhibits topoisomerase I to interfere with DNA synthesis
Uses:
Second-line therapy for colon cancer
Book: Colon, rectal, cervical, and lung cancers
Side effects:
Book: Life-threatening diarrhea (IV atropine in 1st 24 hours, then loperamide 2 mg q2h or 4 mg q4h); myelosuppression, fatigue, alopecia
**UGT1A1 homozygotes have increased risk of febrile neutropenia and diarrhea (may need dose reduction)** |
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Term
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Definition
Class: Classic alkylating agent
Mechanism: Forms an electrophilic compound that chemically binds to DNA, preventing cell division by cross-linking the DNA strands
Uses: Leukemias, lymphomas, breast cancer, ovarian cancer
Side effects:
Hemorrhagic cystitis (from acrolein metabolite irritating mucosa of bladder)
Secondary neoplasm (bladder cancer; acute leukemias)
Alopecia
Nausea/vomiting
Pulmonary toxcitiy
Cardiotoxicity |
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Term
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Definition
Class: Classic alkylating agent
Mechanism: Cyclophosphamide analog; forms electrophilic compound that binds to DNA, cross-linking the strands and preventing cell division
Uses: ALL; lymphomas; breast, ovarian, lung, and head and neck cancers
Side effects:
Hemorrhagic cystitis (always give with MESNA, which binds to acrolein and prevents it from being an irritant to the bladder mucosa)
Secondary neoplasms
Alopecia (less than cyclophosphamide)
Confusion, delirium, and somnolence if infused too quickly |
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Term
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Definition
Class: Non-classical alkylating agent
Mechanism: Forms electrophilic complex, which binds to and disrupts DNA; exact mechanism is unclear, but appears to inhibit DNA, RNA, and protein synthesis
Uses:
Hodgkin's lymphoma (in 4-drug combo)
Melanoma
Soft tissue sarcomas
Side effects
Myelosuppression
Severe nausea and vomiting
Secondary neoplasm
Flu-like syndrome beginning 7 days after treatment and lasting 1-3 weeks |
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Term
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Definition
Class: Heavy metal compound
Mechanism: Forms reactive platinum complex, that forms inter- and intra-strand DNA cross-links to inhibit DNA synthesis
Uses:
Book: Head and neck cancer, anal cancer, lymphomas, carcinoma
Side effects:
Renal toxicity = DOSE LIMITING (give 1 L of fluid before dose and 1 L of fluid with dose)
Ototoxicity and glove-and-stocking neuropathy
Nausea and vomiting = severe |
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Term
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Definition
Class: Heavy metal compounds
Mechanism: Forms reactive platinum compound that binds to DNA and forms inter- and intra-strand cross-links, inhibiting DNA synthesis
Uses:
Book: Ovarian, lung, breast, testicular, esophageal, and head and neck cancers; lymphomas
Side effects: Fewer than cisplatin
Thrombocytopenia
Secondary neoplasm
Nausea and vomiting
Hypersensitivity |
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Term
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Definition
Class: Heavy metal compounds
Mechanism: Forms reactive platinum compound that binds to DNA, forming inter- and intra-strand cross-links that prevent DNA synthesis
Uses:
Metastatic colon cancer
Stage III colon cancer, in combination with 5-FU/leucovorin after resection of primary tumor
Side effects:
Cold-induced neuropathy
Glove-and-stocking neuropathy
Hypersensitivity
Mild nausea and vomiting |
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Term
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Definition
Class: Anthracycline antibiotic
Mechanism:
1. Intercalates between 2 DNA strands to cause structural damage to the DNA
2. Inhibition of topoisomerase II, preventing DNA replication
3. Forms oxygen free radicals that damage DNA
Uses:
Acute Myelogenous Leukemia (AML)
Liposomal formulation: AIDS-related Kaposi's sarcoma
Book: ALL, non-Hodgkin's lymphoma, neuroblastoma, Ewing's sarcoma
Side effects:
Cardiotoxicity (Congestive Heart Failure)
Alopecia
Vesicant SE |
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Term
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Definition
Class: Anthracycline antibiotic
Mechanism:
1. Intercalates between 2 DNA strands to cause structural damage to the DNA
2. Inhibition of topoisomerase II, preventing DNA replication
3. Forms oxygen free radicals that damage DNA
Uses:
Liposomal: Kaposi's sarcoma
Book: Breast, esophageal, bladder, lung, ovarian, and head and neck cancers; lymphomas; multiple myeloma
Side effects:
Cardiomyopathy
Vesicant
Alopecia
Book: myelosuppression, mucositis, nausea/vomiting
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Term
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Definition
Class: Anthracycline antibiotic
Mechanism:
1. Intercalates between 2 DNA strands to cause structural damage to the DNA
2. Inhibition of topoisomerase II, preventing DNA replication
3. Forms oxygen free radicals that damage DNA
Uses:
Acute nonlymphocytic leukemia (AML)
Book: CML, myelodysplastic syndromes
Side effects:
Cardiomyopathy (congestive heart failure)
Vesicant
Alopecia
Book: red-orange urine, mucositis, mild n/v, bone marrow suppression |
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Term
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Definition
Class: Antitumor antibiotic
Mechansim: Causes DNA strand breakage (unknown mechanism)
Uses:
Testicular cancer
Hodgkin's lymphoma
Book: squamous cell carcinoma of skin, Kaposi's sarcoma
Side effects:
Pulmonary toxicity (pneumonitis: dry cough, dyspnea, rales, and infiltrates)
Chills and fever
Pseudoanaphylaxis
Alopecia
Book: nausea and vomiting |
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Term
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Definition
Class: Microtubule-targeting drugs
Mechanism: Binds at ends of microtubules, inhibiting microtubule dynamics (which inhibits cell division); analog of halichondrin B, which is found in marine sponges
Use:
Metastatic breast cancer after previous treatment with anthracycline, taxane, and at least 2 chemotherapy regimens
Side effects:
Not listed |
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Term
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Definition
Class: Aromatase inhibitor
Mechanism: Inhibit conversion of androgen precursors to estradiol
Uses:
Book: Adjuvant for hormone positive breast cancer in postmenopausal women and in patients with disease progession after tamoxifen
Side effects:
Book: hot flashes, arthralgias, osteoporosis/bone fractures, thrombophlebitis |
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Term
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Definition
Class: Aromatase inhibitor
Mechanism: Inhibit conversion of androgen precursors to estradiol
Use:
Book: Hormone receptor positive or unknown advanced breast cancer in postmenopausal women
Side effects:
Book: Bone pain, hot flashes, back pain, nausea, arthralgia, osteoporosis and bone fractures, dyspnea |
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Term
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Definition
Class: Antiandrogen
Mechanism: Block androgen receptors to inhibit action of testosterone and dihydrotestosterone in prostate cancer cells
Use:
Prostate cancer
Side effects:
Book: hot flashes, gynecomastia, and decreased libido |
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Term
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Definition
Class: Luteinizing Hormone Releasing Hormone (LHRH) analogues
Mechanism: Initially increase estrogen and testosterone release, but eventually (in 1-2 weeks) cause decrease due to continuous negative feedback loop
Use:
Hormone-responsive cancers (breast cancer and prostate cancer)
Side effects:
Book: testicular atrophy, decreased libido, gynecomastia, hot flashes |
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Term
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Definition
Class: Luteinizing Hormone Releasing Hormone (LHRH) analogues
Mechanism: Initially increase estrogen and testosterone release, but eventually (in 1-2 weeks) cause decrease due to continuous negative feedback loop
Use:
Hormone-responsive cancers (breast cancer and prostate cancer)
Side effects:
Book: testicular atrophy, decreased libido, gynecomastia, hot flashes; subcutaneous pellet, so pre-medication with lidocaine can help reduce pain |
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Term
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Definition
Class: LHRH pure antagonist
Mechanism: Binds to LHRH receptors in the pituitary, preventing testosterone and estrogen release
Don't get the initial surge that you get with LHRH analogues
Use:
Advanced prostate cancer
Side effects:
Wikipedia: Hot flashes, weight gain, injection site pain |
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Term
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Definition
Class: Selective estrogen receptor modulator (SERM)
Mechanism: Competes with estrogen for binding to estrogen receptors, then the estrogen receptor-tamoxifen complex translocates to the nucleus and recruits co-repressors to prevent genes from being turned on (decrease DNA synthesis and prevent estrogen effects)
Uses:
Stage 4 breast cancer
Adjuvant for micrometastatic disease in Stage 1-3 breast cancer
Prevention of breast cancer for women at increased risk (decreases risk by 50%!)
Book: Hormone-receptor positive breast cancer in postmenopausal women
Side effects:
Book: Hot flashes, fluid retention, mood swings, endometrial and uterine cancer, corneal changes/cataracts |
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Term
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Definition
Class: Biologic response modifier (monoclonal antibody)
Mechanism:
Binds to CD20 on B cells and induces apoptosis
Book: Binds to CD20, which is expressed on B cells, and mediates cell death by antibody-dependent cellular toxicity
Use:
Subset of lymphoma patients
Book: CD20+ B-cell lymphoma
Side effects:
Chills and fever
Book: hypersensitivity, hypotension, rash, HA, mild n/v |
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Term
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Definition
Class: Biologic response modifier (monoclonal antibody)
Mechanism:
Binds to HER-2/neu and arrests cells in G1 phase
Book: Antibody against human epidermal receptor-2 (HER-2), which is overexpressed on 25-30% of breast cancer cells
Use:
Breast cancer treatment for women who are HER-2/neu positive
Side effects:
Cardiomyopathy (book: congestive heart failure) when given with anthracycline antibiotics
Chills and fever
Book: hypersensitivity, rash, diarrhea, cough, headache, insomnia |
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Term
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Definition
Class: Biologic response modifier (monoclonal antibody)
Mechanism:
Binds externally to epidermal growth factor receptor (EGFR) on surface of cells, which blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreases matrix metalloproteinase and vascular endothelial growth factor production
Use:
Metastatic colon cancer
Book: Head and neck cancer; Does NOT respond to metastatic colon cancer with KRAS mutation, so must test
Side effects:
Chills and fever
Book: acne-like rash on face and upper torso, hypersensitivity, interstitial lung diseae, abdominal pain, n/v |
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Term
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Definition
Class: Biologic response modifier (monoclonal antibody)
Mechanism:
Book: Binds to Vascular Endothelial Growth Factor (VEGF) preventing it from binding to its receptors, which results in inhibition of angiogenesis
**Note: this drug does NOT bind to a cell surface antigen!
Use:
Metastatic colorectal cancer (combo w/ 5-FU = first line!)
Book: Kidney, breast, lung, and head and neck cancer
Side effects:
Chills and fever
Book: Hypertension, impaired wound healing, thrombolytic events, proteinuria, bleeding, perforation |
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Term
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Definition
Class: Signal transduction inhibitor (BCR-ABL tyrosine kinase inhibitor)
Mechanism:
Blocks the action of BCR-ABL tyrosine kinase by binding to the ATP binding site (kinase pocket); interferes with pathway that signals growth in tumor cells while having little effect on normal cells
Use:
CML
Book: ALL also
Side effects:
Chills and fever
Book: INX with CYP3A4 inducers/inhibitors |
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Term
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Definition
Class: EGFR tyrosine kinase inhibitor (Signal transduction inhibitor)
Mechanism: Prevents EGFR-mediated stimulation of intracellular signaling pathways, thereby resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and VEGF production.
Uses:
Non-small cell lung cancer
Pancreatic cancer
Side effects:
Book: Interstital lung disease, rash, diarrhea, anorexia, pruritis, conjunctivitis; INX with CYP3A4 inducers/inhibitors |
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Term
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Definition
Class: mTOR inhibitors (serine/threonine kinase inhibitors; signal transduction inhibitors)
Mechanism: Inhibitors mTOR serine-threonine kinase, blocking translation of genes that increase cell growth
Uses:
Renal cell carcinoma: after failure of sunitinib or sorafenib
Metastatic post-menopausal, hormone receptor +, HER-2 negative breast cancer
Side effects: Not listed |
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Term
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Definition
Class: Serine-threonine kinase inhibitor
Mechanism: Targets serine/threonine kinase produced by mutated BRAF gene
Use:
Malignant melanoma with mutated BRAF gene; required genomic testing (approved August 2012)
Side effects: Not listed |
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Term
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Definition
Class: Proteasome inhibitor
Mechanism: Inhibits proteasome, which results in decreased cell growth and proliferation and a pro-apoptotic effect. The proteasome degrades ubiquitinated proteins.
IκB is often ubiquitinated and degraded in cancer.IκB is an inhibitor protein that prevents NFκB from entering the nucleus and activating genes for cell growth and proliferation. So, when ubiquitination is up-regulated, as it is in cancer,IκB gets degrades more, allowing more NFκBto enter the cell, resulting in more cell proliferation. This drug stops this process by stopping the proteasome from chewing upIκB.
Uses:
Refractory mantle cell lymphoma
Untreated multiple myeloma
Side effects:
Micromedex: Peripheral neuropathy, myelosuppression, nausea, vomiting, constipation |
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Term
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Definition
Class: Miscellaneous agent; enzyme
Mechanism: Enzyme from E. coli
Book: Hydrolyzes asparagines to aspartic acid and ammonia, depleting asparagine in the lymphoid cells and preventing protein synthesis
Uses:
ALL
Book: Childhood AML
Side effects:
Anaphylactic reaction (Book: Occurs when doses are >7 days apart; observe closely)
Pancreatitis
Hepatotoxicity: Elevation of LFTs
Chills and fever
Book: fibrinogen depletion |
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Term
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Definition
Class: Miscellaneous agent (anthracycline derivative)
Mechanism: Inhibits topoisomerase II
Uses:
Book: Acute leukemias; breast and prostate cancer; non-Hodgkin's lymphoma
Side effects:
Less likely to cause cardiomyopathy compared to anthracyclines
Book: myelosuppression, mucositis, n/v, cardiac toxicity |
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Term
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Definition
Class: Monoclonal antibody (Biologic response modifier)
Mechanism: Targets CD52 antigen on surface of essentially all B and T lymphocytes
Use:
CLL
Side effects:
Chills and fever
Book: SEVERE immunosuppression; prophylaxis with cotrimoxazole and antivirals |
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Term
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Definition
Class: Monoclonal antibody (biologic response modifier)
Mechanism: Binds to EGFR (book: results in inhibition of cell growth and induction of apoptosis)
Use:
Colorectal cancer after FU, oxaliplatin, and irinotecan containing therapies have been tried
Currently no data on improving overall survival
Book: NOTE: does NOT require KRAS mutation
Side effects:
Chills and fever
Book: Dermatitis, pruritis, exfoliative rash, infusion reactions, pulmonary fibrosis, diarrhea, hypomagnesemia, hypocalcemia, photosensitivity
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Term
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Definition
Class: Monoclonal antibody (biologic response modifier)
Mechanism: Binds to and inhibits CTLA-4, preventing CTLA-4 from exerting its activity of down-regulating T cell activation; therefore T cell activation is increased
Use:
Unresectable or metastatic melanoma (approved in 2011)
Side effects:
Chills and fever |
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