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129 Cards in this Set
- Front
- Back
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What are the 3 goals of treatment of antineoplastic agents?
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1. cure
2. prolong survival 3. relief of symptoms |
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What are the general things that we must monitor when administering antineoplastics?
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1. hematopoietic
2. renal 3. liver 4. neurotoxicity 5. GI symptoms 6. cardiac 7. pulmonary |
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What are we looking for when monitoring hematopoietic side effects with antineoplastics?
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We must monitor CBC with platelets and differential. Most often chemotherapy is delayed until counts are recovered.
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What are we looking for when monitoring renal side effects with antineoplastics?
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monitor serum Creatinine (some chemo and biologics are cleared by the kidney)
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What are we looking for when monitoring liver side effects with antineoplastics?
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Transaminases are markers of hepatocellular death. GGT, alkaline phosphate, and bilirubin are markers of cholestasis or bile duct injury.
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What is the mechanism of alkylating agents?
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They act through the covalent bonding of alkyl groups to cellular molecules. They produce alkylation of DNA through reactive intermediates that attack nucleophilic sites.
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Where do alkylating agents work?
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They are cell cycle non-specific and therefore dose dependent. They act on non-proliferating tumors.
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What are the main toxicities of alkylating agents?
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-bone marrow suppression
-nausea and vomiting -pulmonary toxicity -sexual dysfunction and sterility |
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Which drugs cause pulmonary toxicities?
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-alkylating agents
-all agents starting with "B" |
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What are special considerations regarding cyclophosphamide (Cytoxan)?
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Watch for hemorrhagic cystitis secondary to phosphoramide mustard and acrolein build-up in the bladder
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What are the main alkylating agents?
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cyclophosphamide (Cytoxan)
ifosphamide (IFEX) melphalan (Alkeran) busulfan (Myleran) |
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What monitoring is needed with cyclophosphamide (Cytoxan)? How negative effects be prevented?
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Monitor urine output during therapy and blood in the urine
This can be prevented with hydration, or Mesna given gram/gram (binds to acrolein in bladder) |
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What are special considerations of ifosphamide? What needs to be monitored? How can this be prevented?
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Watch for hemorrhagic cystitis secondary to phosphoramide mustard and acrolein build-up in bladder. Monitor for urine output during therapy and blood in urine. This can be prevented with hydration and Mesna given gram/gram (binds to acrolein in the bladder)
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What are special considerations of melphalan (Alkeran)? What needs to monitored for this? How can this be prevented?
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Must watch for seizures with high dosages used in BMT. Monitor CNS toxicity. Prevent with phenytoin.
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What are special considerations with busulfan (Myleran)? What needs to be monitored with this? How can this be prevented?
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Watch for pulmonary fibrosis and monitor respiration. Also watch for seizures with high dosages used in BMT. Monitor seizure precautions and prevent with phenytoin.
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What are the main heavy metal alkylating agents?
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cisplatin
carboplatin oxaliplatin |
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What is cisplatin used for?
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non-seminoma testicular cancer
lung cancer ovarian cancer head and neck cancer transitional bladder cancer |
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What must you check before giving cisplatin? What adjustments must be made in this case?
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Cisplatin is renally eliminated so we must check SrCr. If CrCl is 10-50, administer 75% of the recommended dose. If CrCl is less than 10, administer 50% of the recommended dose.
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How do you measure a dose for carboplatin?
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Total dose = AUC X (CrCl + 25)
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What are special considerations with cisplatin? What needs to be monitored with this? How can this be prevented?
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We must watch for renal toxicity, emeticity, and neurotoxicity. We can monitor Cr, urine output, Mg, and K. Renal toxicity can be prevented with hydration, mannitol, or amifostine. It also helps to premedicate and administer in at least 1/3 NS.
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What are special considerations with carboplatin? What should we monitor?
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We must watch for bone marrow suppression. Monitor CBC with platelets.
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What are special considerations with oxaliplatin? What should we monitor?
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We must watch for neurotoxicity. Monitor for acute neurotoxicity (less than 14 days) and chronic neurotoxicity (greater than 14 days).
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How do antimetabolites work?
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They work in one of two ways. They compete with normal metabolites for enzyme sites. They can also substitute for metabolites that are normally incorporated into RNA and DNA.
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At what stage are antimetabolites most effective?
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S phase
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What are the main side effects of antimetabolites?
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-bone marrow suppression
-mucositis (sores in mouth and esophagus seen with a drop in platelets) -diarrhea -alopecia duration of exposure increase toxicity |
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What are the main antimetabolites we need to know?
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methotrexate
5-fluorouracil capecitabine (Xeloda) cytarabine (Ara-C) gemcitabine fludarabine 6-mercaptopurine |
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What is the mechanism of methotrexate?
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competitive inhibitor of dihydrofolate reducatase (which converts dihydrofolate to the enzyme tetrahydrofolate)
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What is the mechanism of 5-fluorouracil?
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blocks thymidylate synthase; also is incorporated into RNA and blocks RNA function
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What is the mechanism of capecitabine (Xeloda)?
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it is an oral prodrug of 5-fluorouracil (blocks thymidylate synthase)
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Antimitochondrial antibodies
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Primary biliary cirrhosis
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What is the mechanism of gemcitabine?
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inhibits ribonucleotide reductase, which is responsible for catalyzing the reactions that generate the deoxynucloside triphosphates for DNA synthesis
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What is the mechanism of fludarabine?
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purine nucleoside
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What is the mechanism of 6-mercaptopurine?
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inhibits de novo purine synthesis
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What must we consider with 5-fluorouracil and how can we treat it?
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Watch for diarrhea, treat with anti-diarrheal such as loperamide or Lomotil
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What must we consider with cytarabine?
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Watch for bone marrow suppression
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What must we watch for with gemcitabine?
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myelosuppression (which is dose-limiting)
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What must we watch for with fludarabine and what should we monitor?
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myelosuppression (which is dose-limiting); monitor CBC and monitor for infection (opportunistic infections)
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What must we watch for with 6-mercaptopurine?
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6-MP is deactivated by xanthine oxidase, therefore a 75% reduction is needed in the dose of 6-MP for allopurinol patients.
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What is the mechanism of antitumor antibiotics?
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intercalation with DNA leading to apoptosis
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What adverse effects are associated with antitumor antibiotics?
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-sensitivity reactions
-bone marrow suppression and mucositis -nausea and vomiting is generally moderate |
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What special considerations are noted with doxorubicin (Adriamycin)?
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It is a vesicant that can cause deep ulceration with tissue necrosis (treat with ice pack)
Causes "radiation recall" which is inflammation at a site of radiation Causes many cardiac problems Causes chronic (serious) cardiomyopathy which is permanent It is dose dependent Life time dose is 550mg/M2. |
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What is indicated for patients who have received 300mg/M2 of doxorubicin in their lifetime?
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Dexrazoxane binds iron to prevent iron radical complexes forming with doxorubicin.
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What special considerations are noted with bleomycin?
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Watch for pulmonary toxicities such as wheezing. Interstitial pneumonitis leads to fibrosis which leads to hypoxia (death)
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What is the mechanism of vinca alkaloids?
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They are mitotic inhibitors or "spindle poisons" (they inhibit assembly of microtubule)
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What are the major vinca alkaloids?
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vincristine
vinblastine |
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What is vincristine used for?
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-acute lymphocytic leukemia
-lymphomas -solid tumors |
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What are the major toxicities of vincristine?
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It is neurotoxic (dose-limiting). This affects sensation and motor function (reflexes, paresthesias); cranial nerves (palsies, jaw pain); and autonomic neuropathy (constipation, orthostatic hypotension)
It also is vesicant that requires a warm compress if it extravasates. Also, non-myelosuppression and SIADH |
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What needs to be monitored with vincristine?
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Neurologic function (make them walk on heals, climb stairs, button shirt)
Start patient on laxatives to prevent constipation |
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What is vinblastine used for?
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-lymphomas
-testicular cancer -head and neck cancer -renal cell |
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What are the toxicities of vinblastine?
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-myelosuppression is dose-limiting
-it is a vesicant that may require a warm compress |
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What is the main toxicity of vinorelbine?
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myelosuppression is the dose limiting toxicity
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What is the mechanism of taxane alkaloids?
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promote microtubule assembly and interfere with microtubule disassembly
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What are the major taxane alkaloids?
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paclitaxel
docetaxel |
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What are the major toxicities of paclitaxel?
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-myelosuppression (dose-limiting) - minimize infusion times to no more then 6 hours
-neurotoxic - peripheral neuropathy -hypersensitivity reactions - premedicate with steroids or antihistamines (originally formulated in Cremophor EL, new formulation uses albumin instead and has less hypersensitivity) |
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What are the major toxicities of docetaxel?
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-Myelosuppression is the dose-limiting side effect (watch WBC)
-Hypersensitivity reactions are less common but should still premedicate with corticosteroids for 3 days -Fluid retention is common with edema, weight gain, pleural effusions; premedicate with corticosteroid for 3 days |
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What are the main topoisomerase II inhibitors?
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etoposide
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What is the mechanism for topoisomerase II inhibitors?
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cause double-stranded DNA strand breaks
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What are the uses of etoposide?
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-small cell lung cancer
-non-seminomatus testicular cancer -NHL |
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What are the adverse effects of etoposide?
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-myelosuppression is dose limiting
-orthostatic hypotension is related to rate of administration (slow infusion over 30 minutes to 1 hour) |
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What are the main topoisomerase I inhibitors?
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irinotecan
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What is the mechanism of topoisomerase I inhibitors?
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causes single-stranded DNA strand breaks
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What are the major toxicities of irinotecan?
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-myelosuppression is dose-limiting
-diarrhea can be dose-limiting; acute diarrhea is a cholinergic process and is managed or prevented with atropine; chronic diarrhea is treated with high dose loperamide |
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What monitoring is required with irinotecan?
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-monitor for diarrhea and treat acut with atropine and chronic with loperamide
-monitor for dehydration and electrolyte imbalance |
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What is the mechanism of L-asparaginase?
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Some tumors cannot produce asparagine, whereas in a normal cell L-asparaginase deaminates stores of asparagine, thereby depriving tumor cells of this amino acid
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What is L-asparaginase used for?
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acute lymphocytic leukemia
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What is important to remember with L-asparaginase?
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give test dose
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What are the major biologic modifiers?
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interleukin-2
interferon |
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What is the mechanism of interleukin-2?
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It augments the function of cytolytic T cells, NK cells, LAK cells, and TIL (tumor infiltrating lymphocytes). This stimulates T and B cells.
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What are the uses of interleukin-2?
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renal cell carcinoma
melanoma |
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What do we need to monitor with interleukin-2?
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-capillary leak syndrome (treat with vasopressin, this is dose limiting)
-monitor skin, renal function, LFTs |
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What is the mechanism of interferon?
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Is cytotoxic, cytostatic, and produces differentiation. Causes stimulation of effector cells (NK cells, T cells, and macrophages)
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What are the uses of interferon?
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-Kaposi's sarcoma
-chronic myelogenous leukemia -renal cell |
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What is the mechanism of hormonal agents and steroids in cancer therapy?
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hormonal agents either block or decrease the production of estrogens (breast cancer) or testosterone (prostate cancer)
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What are the selective estrogen receptor modulators?
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tamoxifen
raloxifene |
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What are the major toxicities of selective estrogen receptor modulators?
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thrombotic events
hot flashes nausea uterine cancer |
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What is tamoxifen use for?
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prevention, adjuvant, and treatment of advanced breast cancer
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Patient education for tamoxifen?
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-can induce ovulation
-reduces incidence of breast cancer -need regular gynecologic exams -report any pain/swelling/tenderness of legs or calves (thrombosis) -women need to use birth control |
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What is raloxifene used for?
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prevention of breast cancer
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How is raloxifene different from tamoxifen?
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it has less uterine cancer and thrombotic events
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What are the major aromatase inhibitors?
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letrozole (Femara)
anastrozole (Arimidex) |
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What is the mechanism of aromatase inhibitors?
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blocks the conversion of androgens to estrogens in post-menopausal patients; aromatase inhibitors are not useful in pre-menopausal women because they produce their own estrogen
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What is the main toxicity of aromatase inhibitors?
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osteoporosis
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What are the 2 important anti-androgen therapies?
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ketoconazole
LHRH agonists (leuprolide, goserelin, triptorelin) |
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What are the LHRH agonists?
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leuprolide, goserelin, triptorelin
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What are the uses of LHRH agonists?
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used as an adjuvant for prostate cancer and to treat advanced prostate cancer
also used in premenopausal breast cancer |
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What is the mechanism of LHRH agonists?
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they produce castration levels of testosterone resulting in the terminology "chemical castration"
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What are the adverse effects of LHRH agonists?
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-libido, hot flashes, impotence
-flare reaction -prostate tumors/urinary obstruction -spinal cord lesions - paralysis, leg pain/numbness -flare reactions can be reduced with co-administration of an androgen antagonist for 2 weeks |
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How does ketoconazole work as an anti-androgen therapy?
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interferes with the production of testosterone and other hormones
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What are the uses of steroid in cancer therapy?
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antiemetic, anti-inflammatory in bone metastasis, appetite stimulant, decreases adverse effects
-steroids are also used as an antineoplastic in leukemias and lymphomas, primarily those of B cell or plasma cell |
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Steroids have many adverse effects, but which important one do they avoid?
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they DO NOT cause neutropenia (although there is an increased risk of infection)
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What is the mechanism of traztuzumab (Heceptin)?
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binds to HER-2 receptor causing antibody-dependent cell lysis
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What are the uses of traztuzumab (Heceptin)?
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breast cancer
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What are special consideration with traztuzumab (Heceptin)?
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anaphylaxis and pulmonary toxicities; cardiomyopathy which is increased with doxorubicin or adriamycin use; monitor cardiac function
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What is the mechanism of rituximab (Rituxan)?
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is a monoclonal Anti-CD20 that binds to CD20 on B-cells cuasing antibody-dependent or complement-dependent cell lysis
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What are special considerations with rituximab (Rituxan)?
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watch for tumor lysis syndrome and severe mucocutaneous reactions
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What is the mechanism of alemtuzmab (Campath)?
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monoclonal anti-CD52 that binds to CD52 causing antibody-dependent cell lysis on all B and T cells as well as NK cells and macrophages
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What are special considerations with alemtuzmab (Campath)?
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myelosuppression and infections
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What is the mechanism of gemtuzumab ozogamicin (Mylotarg)?
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monoclonal antibody (CD33) is conjugated to antitumor antibiotic (calicheamicin); binds to CD33 forming complex that is internalized, claicheamicin is released in cell causing double-stranded DNA breaks
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What is the mechanism of bevacizumab (Avastin)?
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monoclonal Anti-VEGF (vascular endothelial growth factor); human VEGF mediates neoangiogenesis; over expression of VEGF correlates with a greater risk of metastasis and poor prognosis
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What is bevacizumab (Avastin) used for?
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colorectal cancer
non-small cell lung cancer breast cancer |
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What are special considerations with bevacizumab (Avastin)?
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Watch for epistaxis; impaired wound healing/old wound breakdowns; DVT
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What is the mechanism of cetuximmab (Erbitux)?
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Monoclonal Anti-EGFR (epidermal growth factor receptor); cell cycle inhibition (G1) and a decrease in antigen expression
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What is mechanism of thalidomide (Thalmid)?
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anti-angiogenic immunomodulatory drug that inhibits angiogenesis
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What are the uses of thalidomide (Thalmid)?
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multiple myeloma
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What are special considerations with thalidomide (Thalmid)?
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Neuropathy
Coagulapathy (DVTs; use heparin) Sedation Constipation Known teratogen |
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Lenalidomide general information
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Same as mechanism as thalidomide but has dose-limiting myelosuppression and more DVTs, but less sedation and neuropathy
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What is the mechanism of imatinib (Gleevac)?
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tyrosine kinase inhibitor causes apoptosis in Philadelphia chromosome-(+) cells (CML)
this is an oral medication |
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What is the mechanism of bortezomib (Velcade)?
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specific/selective inhibitor of the 26S proteasome; proteasome gets rid of cell cycle waste products (build up of waste causes cell death)
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What are the major toxicities associated with chemotherapy?
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1. Hematologic toxicity
2. GI toxicity 3. Skin reactions 4. Cardiac toxicity 5. Pulmonary toxicity 6. Nervous system toxicity 7. Renal toxicities |
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Which agents cause pancreatitis?
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L-asparaginase
corticosteroids cytarabine |
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Which agents cause colitis?
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Doxorubicin in combo with cytarabine has produced fatal necrotizing necrosis
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Which agents cause mucositis and stomatitis?
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Methotrexate
mitomycin 5-fluorouracil thiotepa cytarabine |
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Which agents cause hepatic veno-occlusive disease?
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Dacarbazine
6-mercaptopurine cytarabine azathioprine radiation BMT |
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Which agents cause radiation recall?
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Doxorubicin
busulfan dactinomycin |
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What are the main agents that cause cardiac toxicity? How can these toxicities be minimized?
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Anthracyclines (doxarubicin)
Max dose in lifetime should be 550mg/m2 or 450mg/m2 in high risk patients. High risk include mediastinal radiation, hypertension, preexisting cardiac disease, and over 70 years old. Should not be given to patients with LVEF of <30%. Dexrazoxane binds to iron to prevent iron radical complexes forming with doxorubicin. |
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Which agents cause pulmonary toxicity?
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All agents that begin with a "B" and the alkylating agents
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What are the risk factors for bleomycin regarding pulmonary toxicities?
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Bleomycin leads to pulmonary fibrosis. Risk factors include renal dysfunction, used in combo, doses over 400 units and over 70 years old.
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What pulmonary toxicity is associated with busulfan?
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Interstitial pulmonary fibrosis can progress to pulmonary failure, the so called "busulfan lung"
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What 3 "B's" are associated with pulmonary toxicity?
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busulfan
bleomycin BCNU (carmustine) |
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What are the major agents that cause nervous system toxicity?
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cytarabine
cisplatin busulfan vincristine |
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What nervous system toxicities are associated with cytarabine?
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-cerebral and cerebellar dysfunction
-slurred speech, unsteady gait, dementia coma |
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What nervous system toxicities are associated with cisplatin?
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Generally produces peripheral neuropathies, visual disturbances, and auditory impairment. The peripheral neuropathy is often " stocking and glove"
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What nervous system toxicities are associated with busulfan?
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CNS seizures which are controlled with phenytoin
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What are the nervous system toxicities associated with vincristine?
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Neuropathy, loss of motor and sensory function, "foot drop"
never give this agent intrathecally |
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What are the main agents associated with renal toxicity?
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cisplatin
carboplatin |
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What is the renal toxicity with cisplatin?
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25% of patients experience renal dysfunction due to a metabolite. This leads to hypocalcemia, hypokalemia, and hypomagnesemia.
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What is the renal toxicity of carboplatin compared to cisplatin?
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Carboplatin is 25% less severe than with cisplatin.
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Which agents will cause drug related infertility?
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chlorambucil
cyclophosphamide melphalan mechlorethamine busulfan procarbazine |
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Which agents cause secondary tumors?
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alkylators
azathioprine |
