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rclee06
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Cisplatin, Carboplatin, and Oxaliplatin are what types of agents?
Heavy Metal Alkylating Agents
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What is the MOA of cisplatin, carboplatin, and oxaliplatin?
Forms intrastrand and interstrand DNA cross-links; binding to nuclear and cytoplasmic proteins
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What are the major toxicites associated with cisplatin?
- NephrotoxicitySevere N/V
- Ototoxicity
- Neuropathy
- Electrolyte depletion (Mg, K)
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What are the major toxicities associated with carboplatin?
- Myelosuppression
- Moderate to severe N/V
- Hypersensitivity
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What are the major toxicities associated with oxaliplatin?
- Neuropathy
- Moderate to severe N/V
- Myelosuppression
- Hypersensitivity
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What are the monitoring parameters of heavy metal alkylating agents?
- CBC
- SCr/BUN
- Ins/Outs
- N/V status
- Neurologic function
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Types of cancers that are treated with heavy metal compounds include:
- Lung
- Testicular
- Bladder
- Breast
- Ovarian
- Colorectal
- Head and Neck
- Gastric
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What type of agent are busulfan and bendamustine?
Alkylating agents
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How do alkylating agents work?
Form DNA cross-links, resulting in ihibition of DNA synthesis and function
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Major toxicities of Busulfan and Bendamustine include:
- Myelosuppression
- N/V
- Alopecia
- Sterility/infertility
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What are the monitoring parameters for Busulfan and Bendamustine?
- CBC
- SCr/BUN
- Ins/Outs
- N/V status
- Pulmonary Function
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What are two AEs of alkylating agents specifically related to busulfan?
- Pulmonary Fibrosis
- Skin Pigmentation
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What types of cancer are treated with busulfan and bendamustine?
- Leukemias
- Lymphomas
- Melanoma: by other alkylating agents
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What is the MOA of bleomycin?
DNA strand breakage and free radical formation
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What is the major toxicity associated with bleomycin?
Pulmonary
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Name three Anthracyclines
- Doxorubicin
- Daunorubicin
- Idarubicin
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What is the MOA of anthracyclines?
- Alkylation or intercalation of DNA (insertion of drug molecule between DNA strands)
- Topoisomerase II Inhibition
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Major toxicities of anthracyclines include:
- Myelosuppression
- N/V
- Extravasation
- Mucositis
- Alopecia
- Red urine
- Cardiovascular toxicity
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Monitoring parameters for anthracyclines
- CBC
- T. bilirubin
- Cardiovascular Function
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What are the types of cancers that are treated with anthracyclines?
- Breast
- Ovarian
- Bladder
- Thyroid
- Lymphomas
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Which class of drugs have different adverse effect profiles due to liposomal formulations? [Not sure about this]
Anthracyclines
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Name two folate antagonists
- Pemetrexed
- Methotrexate (MTX)
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What is the MOA of pemetrexted and MTX?
- Inhibits dihydrofolate reductase resulting in blockage of thymidylate and purine synthesis
- Pemetrexted: multitargeted antifolate (GARFT, IT, and dihydrofolate reductase)
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What are the major toxicities of folate antagonists?
- Myelosuppression
- Mucositis
- Pulmonary pneumonitis
- Alopecia
- Stomatitis
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Is hypersensitivity more common in pemetrexed or MTX?
Pemetrexted
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Monitoring parameters for folate antagonists include:
- CBC
- SCr/BUN
- Ins/Outs with high dose
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What is an AE associated with high doses of MTX? What drug is used as a rescue agent for MTX?
- Renal tubular necrosis
- Leucovorin
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What must patients be pre-medicated with if being treated with pemetrexed?
Dexamethasone
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What medications may patients needed after treatment with pemetrexted?
- Folic Acid
- Vitamin B12 Supplements
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What types of cancers are treated with MTX and pemetrexed?
- Lymphoma
- Head & Neck
- Lung: Specifically pemetrexed
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List the pyrimidine antagonists
- Capecitabine
- Cytarabine (Ara-c)
- Fluorouracil (5-FU)
- Gemcitabine
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What is the MOA of 5-FU?
- Inhibits thymidylate synthase (TS)
- Incorporation into DNA and RNA resulting in inhibition of synthesis and function
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Which drug is a pro-drug of 5-FU?
Capecitabine
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What is the MOA of pyrimidine antagonists?
Incorporation into DNA and RNA resulting in inhibition of synthesis and function
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Another name for a pyrimidine antagonists is
Antimetabolite
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What are the major toxicities associated with pyrimidine antagonists?
- Myelosuppression
- Mucositis/Stomatitis
- Diarrhea
- Flu-like syndrome
- "Hand-foot syndrome"
- Neurologic
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Monitoring parameters for pyrimidine antagonists include:
- CBC
- SCr/BUN
- Electrolytes
- Neurologic function
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Capecitabine is available in what formulations?
Capecitabine
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What drug does capecitabine have a black box warning against?
Warfarin
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Rash and conjunctivitis are related to which pyrimidine antagonist?
Cytarabine
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What is a dose limiting rxn with bolux dosing of 5-FU?
Myelosuppression
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What are toxicities that are dose liminting with 5-FU infusion?
- GI toxicities
- Hand-foot Syndrome: palmar-plantar erythrodysesthia
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What types of cancers are treated with pyrimidine antagonists?
- Leukemias
- Lymphomas (Ara-c)
- Pancreatic
- Lung
- Breast (Capecitabine)
- Ovarain (Gemcitabine)
- Head & Neck
- Gastric (5-FU)
- Colon
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Name the vinca alkaloids
- Vincristine
- Vinblastine
- Vinorelbine
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How do vinca alkaloids work?
Bind tubulin and interfere with microtubule assembly (depolymerize microtubule) preventing spindle formation and interfering with mitosis
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What are the toxicities associated with vinca alkaloids?
- Peripheral neuropathy
- Myelosuppression
- Constipation
- SIADH: rare
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Which drugs can never be given intrathecally?
Vinca Alkaloids
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Which vinca alkaloid is more commonly associated with neuropathy?
Vincristine
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What are the monitoring parameters for vinca alkaloids?
- T bilirubin: Hepatic dose adjustment
- CBC
- Neurologic Function
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True or False: Vinca alkaloids are cell cycle specific
True
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What types of ccancer are treated with vinca alkaloids?
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What is the MOA of taxanes?
- Bind tubulin and stabilize microtubules and prevent depolymerization of the mitotic spindle
- Freeze cell in anaphase/telophase
- Microtubules present intracellularly and in neurons
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What are the toxicities associated with taxanes?
- Myelosuppression
- Stomatitis
- Peripheral neuropathy
- Total alopecia
- N/V
- Nail Changes
- Hypersensitivity: Paclitaxel
- Fluid retention: Docitaxel
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True or False: Taxanes do not have to be dose adjusted for hepatic dysfunction
False
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What are the monitoring parameters for taxanes?
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What are the predmedications needed for paclitaxel to minimize hypersensitivity?
- Corticosteroid + H1 blocker + H2 blocker
- ex. dexamethasone + diphenhydramine + famotidine 30 minutes prior to chemo
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What are the premedications given before docetaxel to reduce fluid retention?
- Dexamethasone
- ex. 3-5 days starting 1 day prior to chemo
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What types of cancer are treated with taxanes?
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In what class do irinotecan and topotecan belong?
Camptothecans
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What is the MOA of camptothecans?
- Topoisomerase I Inhibitors
- DNA topoisomerase enzymes relieve torsional strain by inducing strand breaks
- Inhibitors inhibit the resealing of the breaks
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What is the toxicites associated with camptothecans?
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Monitoring parameters for camptothecans include:
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Which medication has the AE of acute and delayed diarrhea syndromes?
Irinotecan
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Topotecan is approved in what type of cancer? Irinotecan?
- Ovarian: topotecan
- Colorectal: irinotecan
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Give an example of a podophyllotoxin
Etoposide
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What is the MOA of etoposide?
- Topisomerase II Inhibitor
- DNA topoisomerase enzymes relieve torsional strain by inducing strand breaks
- Inhibitors inhibit the resealing of the breaks
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What AEs are associated with etoposide?
- Hypotension
- Myelosuppression
- Alopecia
- Mucositis
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Monitoring parameters for etoposide?
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True or False: Etoposide should be given slowly to avoid hypotension
True
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The oral etoposide dose is ___ x greater than IV.
2
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What is the MOA of hydroxyurea?
Ribonucleoside diphosphate reductase inhibitor
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What is the MOA of L-Asparaginase?
Inhibits protein synthesis by hydrolyzing asparagine to aspartic acid and ammonia
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What is the MOA of arsenic trioxide?
Damages/degrades the PML-RAR alpha fusion protein
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What is the MOA of Imatinib?
Inhibits Bcr-Abl tyrosine kinase and other receptor tyrosine kinases
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What is the MOA of erlotinib?
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
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What is the MOA of lapatinib?
multiple receptor tyrosine kinase inhibitor (mrTKI)
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What is the MOA of nilotinib?
mrTKI
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What is the MOA of Dasatinib?
mrTKI
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What is the MOA of everolimus?
Mammalian target of rapamycin (mTOR) inhibitor
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Toxicities for hydroxyurea include:
- Myelosuppression
- Mucositis
- Hepatotoxicity: rare
- Renal Toxicity: rare
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In which medication is a test dose often recommended?
L-Asparaginase
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What are the toxicities associated with L-asparaginase?
- Hypersensitivity
- Hyperglycemia
- Pancreatitis
- CNS effects
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Hydroxyurea: PO or IV?
PO
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What are the toxicities associated with arsenic trioxide?
- Increased QTc
- Peripheral neuropathy
- Musculoskeletal pain
- Hyperglycemia
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Which drugs are known to have p450 interactions?
- Imatinib
- Erlotinib
- Lapatinib
- Nilotinib
- Dasatinib
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Name the AEs associated with imatinib
- D/N/V
- Rash
- Fluid Retention
- Myalgias
- CHF
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What AEs are associated with erlotinib?
- Rash
- Diarrhea
- Anorexia
- Interstitial Lung Disease
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What are the AEs of Lapatinib?
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What are the AEs of nilotinib?
- QT prolongation
- Myelosuppression
- Electrolyte abnormalities
- LFT alterations
- Rash
- Myalgia
- Hyperthyroidism
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Toxicities associated with everolimus include:
Hyperglycemia
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Hydroxyurea is used as treatment for ________
sickle cell disease
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L-asparaginase is used as treatment for ________
- Leukemia
- Elspar: will be D/C in December of 2012
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Arsenic Trioxide is used as treatment for ________
Acute promyelocytic leukemia (APL)
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Imatinib is used as treatment for what cancers?
- Leukemia
- GI stromal tumors (GIST)
- Myelodysplastic diseases
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What cancers are treated with erlotinib?
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What medication is used in the treatment of breast cancer after failure with other therapies?
Lapatinib
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Dasatinib is used as treatment for ________
Leukemia
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Everolimus is used for treatment in what type of cancer after failure with sunitinib or sorafenib?
Renal cell carcinoma
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What drug was approved in 2012 for combination treatment with exemestane in advanced breast cancer?
Everolimus
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What is the major toxicity associated with interferon alpha-2B?
Flu like syndrome: fever, myalgia, weakness, headache
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What do you monitor in a patient receiving interferon alpha-2B?
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Which drug has a black box warning for potential to "cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infections"
Interferon alpha-2b
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What are the AEs associated with interferon alpha-2B?
- Bone marrow suppression
- CNS & neurological effects
- Thyroid changes
- Hepatotoxicity
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What is the MOA of Interleukin-2 (aldesleukin)?
Enhances the proliferation and activation of T-cells and NK cells
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What are the major toxicities associated with interleukin-2?
- Flu like syndrome
- Capillary leak syndromeN/V
- Diarrhea
- Bone marrow suppression
- CNS effects
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What is the black box warning for interleukin-2?
Patients should have normal cardiac and pulmonary function
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What are the monitoring parameters for interleukin-2?
- BP
- EKG
- CBC
- SCr
- Ins/Outs
- Signs of pulmonary edema
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Name the Estrogen Receptor antagonists
- Tamoxifen
- Toremifene
- Raloxifene: selective-estrogen receptor modulator
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What is the MOA of tamoxifen and toremifene?
Inhibit nuclear binding of the estrogen receptor, blocking estrogen stimulation of hormone
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What is the MOA of raloxifene?
Activation and inhibition of various estrogen pathways
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What are the AEs associated with estrogen receptor therapy?
- Hot flashes
- N/V
- Thromboembolic events
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Which class of drug may have decreased efficacy if combined with SSRIs?
Tamoxifen and toremifene
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True or False: Raloxifene can be used in premenopausal women
False
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Anastrozole, letrozole, and exemestane belong to which class of drugs?
Aromatase inhibitors
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What is the MOA of aromatase inhibitors?
Inhibit conversion of androgens to estrogens
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List the AEs associated with aromatase inhibitors
- Hot flashes
- Weight gain
- Edema
- Fatigue
- Bone/joint pain
- Potential for increased fracture risk
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Give an example of a GnRH agonist
Goserelin
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What is the ultimate goal of GnRH agonists?
Decrease testosterone and estrogen concentrations
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What are two examples of LHRH agonists?
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What is the intial AE associated with Goserelin?
A tumor flare
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Antiandrogenic effects common with GnRH and LHRH agonists include:
- Hot flashes
- Decreased libido
- Gynecomastia
- GI disturbances
- Injection site pain
- Decreased bone density
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What type of drugs can be used to treat prostate cancer?
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Name the antiandrogen medications
- Bicalutamide
- Flutamide
- Nilutamide
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What is the MOA of bicalutamide?
- Inhibits testosterone and dihydrotestosterone uptake and binding
- Blocks testosterone surge
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AEs associated with antiandrogens
- Hot flashes
- Gynecomastia
- CNS
- Elevated liver enzymes
- Diarrhea
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Trastuzumab is a ______.
Anti HER-2
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AEs associated with trastuzumab include:
- Infusion related reactions: Fever, Chills, Rigors, hypotension
- Hypersensitivity
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What premedications are required with anti-HER2 therapy?
- Antihistamines
- APAP +/- corticosteroids
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An example of an anti CD 20 medication
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CD20 surface antigens are found on what types of cells
B-lymphocytes
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What is the MOA of rituximab?
Activate complement system by binding to CD20
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AEs associated with anti-CD20 therapy
- Infusion related rxns: fever, chills, rigors, hypotension
- Hypersensitivity
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Rituximab is used to treat what type of cancer?
Lymphoma
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Alemtuzumab is a _______
anti CD-52
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What drug binds to CD-52 antigens present on leukemic lymphocytes and induces cell lysis and death?
Alemtuzumab
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AEs of Alemtuzumab include:
- Infusion like rxns
- Neutropenia
- Lyphopenia
- Infections
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Are pre-medications required for alemtuzumab?
- Yes
- Antihistamine
- APAP +/- corticosteroid
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Which drug is currently used to treat leukemia however may be taken off the market and reformulated for MS treatment?
Alemtuzumab
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Name a VEGF inhibitor
Bevacizumab
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List the major toxicities associated with bevacizumab
- GI perforation
- Impaired wound healing
- Hemorrhage
- Thrombotic events
- Hypertension
- Nephrotic syndrome
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Which medication cannot be given within 28 days of surgery?
Bevacizumab: AE includes impaired wound healing
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Bevacizumab is indicated for what type(s) of cancer?
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Cetuximab is what type of drug?
EGFR
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Major toxicites of cetuximab include:
- Rash
- Infusion rxns
- Nausea
- Diarrhea
- Hypomagnesemia
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Cetuximab is indicated for what type of cancer(s)?
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AEs associated with ofatumumab
- Infusion reactions
- Cytopenias
- Progressive multifocal leukoencephalopathy
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What drug is indicated as second-line for chronic lymphocytic leukemia?
Ofatumumab
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What drug binds to HER-2 extracellulary and blocks it from binding to other signaling factors?
Pertuzumab
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List the major toxicities associated with pertuzumab
- Fetal toxicity
- LV dysfunction
- Infusion reactions
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True or False: Pertuzumab is used for patients with HER-2 local breast cancer in combination with trastuzumab and docetaxel in patients who have failed previous chemotherapy regimens
- False:
- Indicated in metastatic chemotherapy naive patients
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