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82 Cards in this Set
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- Back
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What is Pemetrexed (Alimta0?
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inhibits multiple enzymes involved in folate metabolism and DNA synthesis
used for malignant pleural mesothelioma, non-small cell lung cancer |
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What are the possible side effects of Pemetrexed (Alimta)?
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cutaneous reactions – prevent with dexamethasone 4 mg bid day -1, 0, +1
give folic acid 350-1000 mcg daily and vitamin B12 1000 mcg IM q 9 weeks starting week before initiation and for 21 days after therapy to prevent hematologic and gastrointestinal toxicity |
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What is Ara-C (Cytarabine)?
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Arabinose analog of cytosine
Phosphorylated to active component within cancer cells Inhibits DNA polymerase |
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What are the clinical uses of Cytarabine (Ara-C)?
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Acute leukemias
Non-Hodgkin’s lymphoma No significant activity against solid tumors |
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What are the toxicities of Cytarabine?
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Myelosuppression
(100 mg/M2/day) Alopecia Gastrointestinal Rash—plantar-palmer syndrome |
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What are the toxicities of Cytarabine at high doses?
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(3 g/M2 q12h)
nausea CNS toxicity chemical conjunctivitis, acral erythema |
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What is gemcitabine (Gemzar)?
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MOA & structure similar to cytarabine
Intermittent dosing more effective than continuous dosing Effective for solid tumors Pancreatic cancer NSCLC Achieves intracellular concentrations 20x greater than cytarabine |
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What are the toxicities of Gemzar ( Gemcitabine)?
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Fever and flu-like symtoms
Peripheral edema myelosuppression nause and vomitting (mild) NOT neurotoxic |
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What is Clofarabine (Clolar)?
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Relapsed pediatric ALL
Peds 52 mg/m2 IV daily x 5 days Adults 30-40 mg/m2 IV daily x 5 days AE-skin toxicity-rash to desquamation Used in ALL |
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What is Nelarabine (Aranon)?
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Tcell ALL or Tcell lymphoblastic lymphoma
Peds 650 mg/m2 IV daily for 5 days Adults 1500 mg/m2 IV Day 1,3,5 AE-neurotoxicity |
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What is the mechanism of action fluorouracil?
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fluorinated analog of uracil
prodrug that is metabolized to FdUMP in order to be active FdUMP binds to thymidylate synthase (TS) prevents conversion of uracil (RNA) to thymidine (DNA) stabilizes TS & FdUMP in the presence of leucovorin (given with leucovorin to treat colon cancer) |
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What are the clinical uses of Flurouracil?
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Treatment of solid tumors including breast, colorectal and other GI tumors
Non-oncologic uses: actinic keratoses and noninvasive skin cancers |
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What are the toxicities of flurouracil?
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Myelosuppression (bolus)
Bloody diarrhea (CI) Mucositis (CI) Dermatologic Ocular Nausea and vomiting (mild) Cardiotoxicity (rare) |
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What is Capecitabine (Xeloda®)?
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Oral prodrug of fluorouracil
Metabolized to active component in tumor tissue Use in metastatic colorectal & breast cancer Take BID with food (↓ N/V) Diarrhea, palmar-plantar rash |
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What are the purine analogs
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Inhibit de novo purine synthesis
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What is 6-MP Mercaptopurine?
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Metabolized by xanthine oxidase
↓ dose x 75% if used with allopurinol used in ALL |
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What is Thioguanine (6-TG)?
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No dose reduction required with allopurinol
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What is Fludarabine & Cladribine?
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Immunosuppressive → risk of opportunistic infections
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What are the mitotic inhibitors?
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Vinca alkaloids
Taxanes |
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What are the Vincalakaloids?
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Vincristine (Oncovin)
Vinblastine(Velban) Vinorelbine (Navelbine) |
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What are the taxanes?
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Palitaxel (Taxol)
Docetaxel (Taxotere) |
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What are the mechanism of action of the Vinca alkaloids?
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Inhibit microtubule assembly
Interfere with formation of mitotic spindle Cells accumulate in mitosis |
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What are the mechanism of action of the taxanes?
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Promote microtubule assembly
Interfere with microtubule disassembly |
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What are the clinical uses of the vinca alkaloids?
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Vincristine
ALL, lymphomas, multiple myeloma Neuroblastoma Vinblastine Lymphomas Solid tumors (testicular) Vinorelbine NSCLC |
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What are the toxicities of the Vincristine?
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Neurotoxicity
Constipation Vesicant Extravasation SIADH Do not give Intrathecally |
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What are the toxicities of Vinblastine/Vinorelbine?
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Myelosuppression
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What is Vinorelbine (Navelbine)?
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semi-synthetic vinca alkaloid
used for lung, breast, ovarian, lymphoma toxicities myelosuppression neuropathy nausea and vomiting extravasation alopecia |
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What are the toxicities of the Taxanes?
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Myelosuppression
Mucositis Peripheral neuropathy (cumulative) Alopecia Hypersensitivity reactions* Nausea and vomiting (rare) |
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What do you premedicate the taxane patients with?
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* Premedicate with dexamethasone, H1- & H2-antagonist
--to prevent hypersensitivity reactions |
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What is Ixabepilone (ix-a-BEP-i-lone) Ixempra® (ix-EM-pra)
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Semi-synthetic analog of epothilone B
Binds directly to ß-tubulin on microtubules, leading to suppression of microtubule dynamics Some binding sites overlap with paclitaxel accounts for its activity in taxane resistant patients |
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What is the indications oIxabepilone?
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Treatment of patients with metastatic or locally advanced breast cancer:
In combination with capecitabine in patients resistant to treatment with an anthracycline and a taxane Monotherapy in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine |
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What are Epipodophyllotoxins?
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Etoposide (VP-16) & teniposide (VM-26)
Inhibit topoisomerase II Toxicities Myelosuppression Mucositis (BMT) Hypotension (diluent) Clinical uses VP16 – AML, NHL, BMT, solid tumors (IV or oral) VM26 – ALL, SCLC |
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Whhat are the Campothecins?
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Irinotecan & topotecan
Inhibit topoisomerase I Clinical uses Ovarian cancer Lung cancer CML, MDS Cervical, ovarian cancer Colorectal cancer |
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What are the toxicities of Toptecan?
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Myelosuppresion
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What is the toxicitiy of irontecan?
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Severe diarhea
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What is L-asparaginase?
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Degrades asparagine found in the serum
In lymphoid malignancies the lymphocytes are unable to produce asparagine due to a lack of or low levels of asparagine synthetase and rely on serum asparagine for its needs. Without the serum asparagine the cells are unable to grow and reproduce Used for ALL |
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What are the adverse events with L-aspariginase?
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Adverse Events
pancreatitis (check amylase) *decreased fibrinogen < 100mg% (clotting problems) if low give cryoprecipitate *hypersensitivity reactions, if so give Erwina asparaginase or peg-asparaginase (more expensive) Peg-asparaginase-larger molecule therefore given less frequent |
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What is hydroxyurea of Hydrea?
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Used for CML
Causes myelosuppression Doses 50 mg/kg/d (aprx 500 mg PO BID & titrate to WBC effect) |
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What is Bortezomib (Velcade)?
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Selective, reversible inhibitor of the proteasome
Proteasome: multi-enzyme complex in all cells; degrades proteins and regulates cell-cycle progression Adverse events: peripheral neuropathy, fatigue, malaise, weakness, GI effects, thrombocytopenia Used for Multiple Myeloma, NHL, ? leukemias |
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What is All-trans retinoic Acid (Vesinoid)?
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Used with APL
Matures promyelocytes blasts inducing a CR May cause retinoic acid syndrome that needs to be treated with dexamethasone Dose: 45 mg/m2/d (round to nearest 10 mg) PO divided BID with food up to 90 days Give with cytarabine and daunorubicin Retinoic acid syndrome- fever, dyspnea, pleural effusion, peripheral edema, hypotension treat-dexamethasone 10 mg IV BID x 3 days |
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What is arsenic trioxide (Trisenox) ?
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used for APL
retinoic acid syndrome (differentiation syndrome) when they fail ATRA therapy QTC prolongation--check EKG |
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What is thalidomide ?
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increase risk for thromboembolism--when givev with steroids
multiple myeloma drowsiness peripheral neuropathies pts / prescribers / dispensers must enroll in STEPS --very teratogenic-- |
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What is Lenalidomide (Revlimid)?
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for MDS and MM
Myelosuppression Dose for MDS: 10 mg po day Dose for MM: 25 mg po day |
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What are Hypomethylating Agents?
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Cells need methyl groups to grow
Removes methyl groups leading to cancer cell death |
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What are the hypomethylating agents?
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Azacitadine (Vidaza)
Decitabine (Dacogen) |
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What are Azacitadine (Vidaza)?
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Used for MDS
Given 75-150 mg/m2 SQ or IV daily x 7 days SQ route has local reaction |
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What is Decitabine (Dacogen)
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Used for MDS
15 mg/m2 IV every 8 hours x 9 doses every 6 weeks 20 mg/m2 IV daily x 5 days every 4 weeks |
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Histone Deacetylators (HDACs)
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Cancer cells can have too much HDAC which allows the cell to grow unregulated (unable to die)
If inhibit HDAC, then allows the cell to develop normally and complete cell life Ultimate goal is cell death through normal cell regulation |
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What do histones do?
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Histone: “spools” around which DNA wind
Histones contain lysine-rich amino-terminal tails that are responsible for conformational change by DNA |
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Histone deacetylases (HDACs)
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remove acetyl group to lysine tail, restores charge, increases attraction between histones and DNA → condensation of chromatin → represses transcription
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What is Vorinostat (Zolinza)?
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Some tumor cells produce excess amounts of histone deacetylase (HDAC), leading to a closed chromatin structure and prevention of DNA transcription
HDAC inhibitors have also been shown to: Cause cell cycle arrest Induce apoptosis Inhibit angiogenesis |
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What is the clinical use of Vorinostat (Zolinza)?
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Clinical Use
Cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies |
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What are the side effects of Vorinostat?
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Hematologic abnormalities
Anemia Thrombocytopenia Gastrointestinal symptoms Diarrhea, nausea Taste disorders May prolong QTc interval |
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What is Temsirolimus (Torisel™)?
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mTOR inhibitor
MOA: Inhibition of mTOR blocks translation of mRNA and halts progression from G1 to S phase Treatment of advanced renal cell carcinoma premedicate with antihistamine |
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Temsirolimus: Adverse Events
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Hypersensitivity reactions (9%)
Hyperglycemia / Hyperlipidemia mTOR plays role in glucose and lipid metabolism Immunosuppression Infections and impaired wound healing Bowel Perforation Fatal in 1 patient Renal Failure Interstitial lung disease (2%) |
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What are the Monoclonal Antibodies (Mab) MOA?
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Destroys tumor cells through a number of possible mechanisms, including activation of complement and antibody-dependent cell-mediated cytotoxicity
Useful as means of targeting cytotoxic radioisotopes, toxins, or drugs to tumors, enhancing their delivery to tumors while minimizing systemic exposure Animal (murine/equine), human or chimeric derived |
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How do you name the monoclonal antibodies?
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momab-radiolabeled
tositumomab zumab-human alemtuzumab ximab-chimeric with murine & human cetuximab |
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What are the monoclonal antibodies toxicities?
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Infusion-related toxicity (65-80%): SOB, temp, chills, nausea, asthenia, and HA
premedications—acetaminophen, diphenhydramine, hydrocortisone Hypotension (10%)-recommend holding anti-hypertensives |
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What are the 1st Generation MAB?
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Rituximab (Rituxan)
Gemtuzumab ozogamicin (Mylotarg) Alemtuzumab (Campath) |
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What is Rituximab?
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Anti-CD-20 antigen found on B lymphocytes
Used for B-cell non-Hodgkin’s lymphoma |
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Gemtuzumab ozogamicin (Mylotarg)?
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Anti-CD-33 antigen linked to ozogamicin
Used for Acute melogenous leukemia (AML) Profound bone marrow suppression |
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Alemtuzumab (Campath)
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Anti-CD-52 antigen found on B and T lymphocytes
Used for B-cell chronic lymphocytic leukemia Profound immunosuppression |
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What are the Radiolabelled MAB?
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ibritumomab (Zevalin)
tositumomab (Bexxar) |
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What is ibritumomab (Zevalin)?
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antibody linked to radioactive isotope yttrium-90, directed against CD-20
given with rituximab used in follicular non-Hodgkin’s lymphoma |
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What is tositumomab (Bexxar)?
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antibody linked to radioactive isotope iodine-131, directed against CD-20
used in follicular non-Hodgkin's lymphoma |
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What is Tyrosine Kinase?
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Regulates cellular proliferation, differentiation, function, & survival
Receptor & non-receptor TKs FLT3, VEGF, ABL, c-KIT, etc. Activity tightly controlled in normal cells |
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What are tyrosine kinase inhibitors?
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Small molecule inhibition
Blocks ATP binding to kinase domain Stops intracellular signaling pathways Cellular apoptosis Monoclonal antibodies Target receptor TKs or the ligand Interrupt TK signaling Antibody-mediated cytotoxicity |
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What are the small molecules tyrosine kinase inhibitors?
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Imatinib (Gleevec®)
Gefitinib (Iressa®) Erlotinib (Tarceva®) Sunitinib (Sutent®) Sorafenib (Nexavar |
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Monoclonal Antibodies
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Cetuximab (Erbitux®)
Trastuzumab (Herceptin®) Bevacizumab (Avastin®) |
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What is trastuzumab (Herceptin)?
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binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2) found on some breast cancers
used for metastatic breast cancer whose tumors overexpress the HER-2/neu protein can cause congestive heart failure monolconal antibody for breast Cancer |
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What is bevacizumab (Avastin)?
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antibody against vascular endothelial growth factor (VEGF)
used for metastatic colorectal cancer inhibits blood vessel formation (do not give within a month of surgery) causes hypertension colon cancer |
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What is cetuximab (Erbitux)?
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antibody against epidermal growth factor receptor (EGFR)
used for metastatic colorectal cancer causes acneform rash colon cancer |
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What is Panitumumab (Vectibix)?
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Patients with EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following one or more regimens containing:
Fluoropyrimidine, Oxaliplatin, or Irinotecan 6 mg/kg IV every other week Premedications are necessary Toxicities Pulmonary fibrosis dermatologic toxicity infusion reactions Hypomagnesemia N/V/constipation |
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What are the Tyrosine Kinase Inhibitors against Lung Cancer?
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inhibits epidermal growth factor receptor (EGFR) tyrosine kinase
erlotinib (Tarceva) used as salvage treatment of non-small cell lung cancer causes acneiform rash, diarrhea, interstitial lung disease |
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What is erlotinib (Tarceva) ?
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used as salvage treatment of non-small cell lung cancer
causes acneiform rash, diarrhea, interstitial lung disease |
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What is gefitinib (Iressa)?
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used for non-small cell lung cancer in patients who are benefiting or have benefited from gefitinib
skin rash, ocular symptoms, pulmonary symptoms |
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What are the Tyrosine Kinase Inhibitors against CML?
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inhibits Bcr-Abl tyrosine kinase
Bcr-Abl is the abnormal gene product that is caused by the Philadelphia chromosome in chronic myeloid leukemia (CML) also inhibits tyrosine kinase for platelet derived growth factor (PDGF), stem cell factor (SCF) and c-kit |
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What are the toxicities of the Tyrosine Kinase Inhibitors against CML?
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Musculoskeletal pain
Fluid retention QT prolongation |
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What is Imatinib (Gleevec)?
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used to treat Philidelphia chromosome + CML and Kit-positive gastrointestinal stromal tumors (GIST)
Dose: 400 to 800 mg daily There are a lot of mutations that may be overcome except T315I |
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What is Dasatinib (Sprycel)?
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Adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy including imatinib
Take antacid 2 hrs prior to or after dose Major drug interactions With CYP3A4 inhibitor, decrease dose to 20-40 mg daily Consider increase in dose if given with CYP3A4 inducer |
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What is Nilotinib (Tasigna)?
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Similar indication as dasatinib
No food 2 hours prior to or 1 hour after dose Major CYP3A4 interactions but no official recommendations |
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What are the Tyrosine Kinase Inhibitors against renal cell cancer?
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Sorafenib (Nexavar)
Advanced renal cell carcinoma in adults Sunitinib (Sutent) Gastrointestinal stromal tumors (GIST) after disease progression or intolerance to imatinib Advanced renal cell carcinoma in adults |
