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94 Cards in this Set
- Front
- Back
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What is the significance of EGFR mutations as it relates to drug therapy?
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EGFR mutations (especially exon 19 deletion, exon 21 mutation) are associated with response to Tyrosine Kinase Inhibitors (TKI) such as erlotinib.
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What is the significance of K-ras mutations as it relates to therapy?
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K-ras mutations are associated with TKI resistance. If this is the case, do no use TKI.
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What are the early signs of lung cancer?
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Cough, hoarseness, wheezing, dyspnea
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What are the signs of metastatic spread of lung cancer?
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Hemoptysis, Pancoast's syndrome, Bone pain, Jaundice
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What are the major features of paraneoplastic syndrome? (6)
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SIADH
Elevated ANP Cushings Syndrome Lambert-Eaton Syndrome Superior Vena Cava Syndrome Hypercalcemia |
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What is are the symptoms of Pancoast's Syndrome?
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Shoulder/arm pain due to tumor compression of the brachial plexus
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How do you manage SIADH? (3 things)
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Fluid restriction
Saline infusion for symptomatic patients Demeclocycline |
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What are the symptoms and mechanism of action of Lambert-Eaton Syndrome?
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Symptoms: muscle weakness, followed by increased strength
Mechanism: Insufficient release of ACh by nerve cells--> build up of ACh--> increased strength |
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What are the symptoms of Superior Vena Cava Syndrome?
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Facial swelling, arm swelling, neck swelling, headache, dizziness, fainting, reddening of the face and palms
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True or false? Superior Vena Cava Syndrome occurs more in Small-Cell Lung Cancer.
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True. Superior Vena Cava Syndrome occurs more in Small-cell lung cancer than it does in Non-small-cell lung cancer.
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What is the general treatment for NSCLC?
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Surgery +/- Radiation +/- Chemotherapy
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What is the general treatment of SCLC?
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Radiation, chemotherapy, best supportive care
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Why is surgery usually not an option for SCLC?
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By the time the SCLC is detected, it has already metastasized and is difficult to remove by surgery.
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Surgery is the treatment of choice for what kind of cancer?
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Resectable NSCLC (stage I, II and IIIa)
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Radiation is the treatment of choice for what kind of cancer and patients?
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Unresectable limited cancer
Patients not able to tolerate surgery |
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Chemotherapy is the treatment of choice for what kind of cancer?
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Unresectable spread cancer (stage IV)
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True or false? Chemotherapy is recommended for ECOG performance status 3-4.
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FALSE. Chemotherapy should only be used in ECOG performance status 0-2. Best Supportive Care (BSC) is recommended or patients with ECOG performance status 3-4.
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What is consolidation chemotherapy and when is it indicated?
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Consolidation chemotherapy is a second course of chemotherapy with a higher efficacy. It is considered after concurrent chemoradiation in stage IIIB patients.
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True or false? Concurrent chemotherapy (with surgery) is superior to sequential chemotherapy.
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TRUE
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True or false? In stage IIIB NSCLC concurrent chemoradiation is superior to sequential therapy.
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TRUE. In stage IIIb, concurrent chemoradiation is superior, however it causes more mucositis.
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What is the first line chemotherapy treatment for Non-small cell lung cancer?
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Cisplatin dual therapy
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What agents can be used for cisplatin combination therapy?
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Vinorelbine
Vinblastin Etoposide Pemetrexed Paclitaxel Docetaxel Gemcitabine Irinotecan |
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When should bevacizumab be added on top of the cisplatin dual therapy?
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Addition of bevacizuab on the 2 drug regimen is recommended only for non-squamous NSCLC, no history of hemoptysis, no CNS metastases, no ongoing therapeutic anticoagulation.
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Which chemotherapy drug is indicated for EGFR mutation positive patients?
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Erlotinib
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What is the first line chemotherapy treatment for SCLC?
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Etoposide + Cisplatin
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What is the second line chemotherapy treatment for SCLC?
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Topotecan
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Why is carboplatin used to substitute cisplatin?
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Carboplain reduces the risk of emesis, neuropathy, and nephropathy. So carboplatin can be used when cisplatin isn't tolerated.
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What kind of solution must Cisplatin be mixed in?
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Cisplatin must be placed in a chloride containing solution to avoid chloride displacement. Avoid just using D5W.
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What kind of solution must Carboplatin be mixed in?
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Since carboplatin does not have the chloride groups, you can use D5W or normal saline.
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How is cisplatin primarily eliminated? And what implications does this have about dosing?
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Cisplatin is mainly eliminated by the kidney.
So dose adjustment is needed with kidney dysfunction. |
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What drugs does cisplatin interact with?
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Nephrotoxins (Aminoglycosides, Amphotericin B)
Ototoxins (loop diuretics) |
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When and how should cisplatin be administered?
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Given early in the morning (monitor side effects over the day).
Pre and post hydration: 1-2 liters NS (with 20 KCL & 8 Mag) Given as a slow 1-2 hour infusion |
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Describe the protein binding of cisplatin
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Rapidly bound to protein
Unbound drug is rapidly eliminated |
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Describe the protein binding of carboplatin
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Slower and less exensive protein binding
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By what route is carboplatin eliminated?
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Elimination is primarily by the kidney 60-70% unchanged
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How should carboplatin be administered?
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Placed in NS or D5W. Administered over 15-30 minutes.
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What kind of needles should be avoided for cisplatin and carboplatin administration?
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Aluminum needles. They cause precipitation and loss of potency.
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What is the dose limiting toxicity(ies) for Carboplatin?
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Bone Marrow Suppression (BMS)
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What is the dose limiting toxicity(ies) for Cisplatin?
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Nausea and vomiting, Neurotoxicity, Nephrotoxicity
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Gemcitabine
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Gemzar
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Cisplatin
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Platinol
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Carboplatin
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Paraplatin
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How is gemcitabine eliminated?
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Primarily through the kidney as a metabolite.
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What phase does gemcitabine work on?
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S phase
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What is the dose limiting adverse effect for gemcitabine?
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BMS
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Which agents are found in the epipodophyllotoxin class?
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Etoposide and Teniposide
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What is the mechanism of Etoposide and Teniposide?
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Inhibits topoisomerase II
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What are the adverse reactions of Gemcitabine?
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Hematologic: BMS (dose limit)
Derm: rash and itching Cardio/resp: dyspnea and hypotension (infusion reactions), peripheral edema Nephrotoxicity: proteinuria, hematuria |
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What additive is used for Etoposide?
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PEG (polyethylene glycol)
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What additive is used for Teniposide?
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CremophorEL
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What agents can be used to treat hypersensitivity caused by the additives in Etoposide and Teniposide? (Hint: 4 agent...CAVE)
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Corticosteroids
Antihistamines Volume expanders Epinephrine |
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Which has higher protein binding: Etoposide or Teniposide?
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Teniposide has higher protein binding (>97%) compared to Etoposide (95%)
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By what route is etoposide cleared?
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Mostly renal
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By what route is teniposide cleared?
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Mostly hepatic
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What dose formulations are available for etoposide?
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IV, PO
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What dose formulations are available for teniposide?
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IV
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What are the adverse reactions of etoposide and teniposide? (Hint:BIN HAM)
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BMS (dose limiting)
Infusion reactions (hypotension, fever, chills) N&V Hyperbilirubinemia Alopecia (moderate) Mucositis |
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What agents are captothecin derivatives?
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Irinotecan
Topotecan |
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What is the mechanism of action for Irinotecan and Topotecan?
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Inhibit topoisomerase I which is involved in single strand breaks
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By what route is irinotecan eliminated?
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Biliary
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By what route is topotecan eliminated?
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Renal
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Why is an acidic environment favored for irinotecan and topotecan?
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Irinotecan and topotecan undergo pH dependent hydrolysis of the E-ring lactone to an open hydroxyl acid. In acidic environment, the closed lactone form is favored and this is the form that exerts antitumor effects.
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Which solvent should be used for campothecin derivatives?
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D5W - this is more acidic than normal saline
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True or false. Irinotecan is a prodrug that is converted to the more active SN-38.
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True
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What are the adverse reactions of irinotecan? (Hint: BED MAN)
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BMS
Eosinophilia Diarrhea Mild hand foot syndrome Alopecia Nausea and vomiting |
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What are the adverse reactions of topotecan? (Hint: BED MAN)
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BMS
Eosinophilia Diarrhea Mild hand foot syndrome Alopecia Nausea and vomiting |
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List the agents that are Vinca Alkaloids...
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Vinblastine
Vincristine (Oncovin) Vinorelbine |
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What is the mechanism of action of vinca alkaloids?
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Stop microtubule assembly arresting mitosis.
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Order these agents by decreasing half life:
Vinorelbine, Vincristine, Vinblastine |
Vincristine>Vinorelbine>Vinblastine
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What is the one benefit Vincristine has over Vinorelbine and Vinblastine in terms of adverse effects?
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Vincristine DOES NOT cause bone marrow suppression.
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What are the general adverse reactions caused by vinca alkaloids? (MEN SAP)
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Myelosuppression (except for Vincristine)
Extravasation Neurotoxicity SIADH Alopecia Pain in tumor site |
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What are the drug interactions caused by vinca alkaloids?
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CYP 3A4 substrate
Decrease digoxin and phenytoin |
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What is the antidote for extravasation?
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Hyaluronidase or warm compression.
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What are the adverse reactions of ifosfamide?
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Myelosuppresion
N&V Hemorrhagic cystitis Alopecia Reproductive failure Secondary neoplasm Neurological |
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What can be done to prevent hemorrhagic cystitis?
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Hydration
Administer in the morning MESNA |
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What is the mechanism of action of Pemetrexed?
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Multitargeted folate: Inhibits
Thymidylate Synthase (TS) Dihydrofolate reductase (DHFR) Glycinamide Ribonucleotide Formyltransferase (GARFT) |
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Pemetrexed
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Alimta
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By what route is Alimta eliminated?
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Renal
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What are the adverse reactions caused by Pemetrexed?
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BMS -dose limiting
Neurotoxicity - dose limiting Cutaneous reaction (skin rash) |
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What can be given to reduce the incidence and severity of the cutaneous reaction caused by Pemetrexed? Please indicate the dose.
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Dexamethasone 4mg PO BID (the day before, day of, and day after administration)
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What agents can be given to reduce the BMS and neurotoxicity caused by Alimta?
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Folic acid (400mcg)
Vitamin B12 (1000mcg) |
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What drug should be avoided when taking Pemetrexed and why?
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NSAIDs cause nephrotoxicity by reducing the clearnace of pemetrexed
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What is the mechanism of action of Bevacizumab?
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Recombinant monoclonal antibody to vascular endothelial growth facor (VEGF).
Bevacizumab binds to VEGF and prevents interaction with it's receptors --> reduction of microvascular growth and inhibition of metastatic disease progression. |
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Bevacizumab
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Avastin
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When should bevacizumab be added to the two drug regimen?
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Recommended only for non-squamous NSCLC, no history of hemoptysis, no CNS metastases, no ongoing therapeutic anticoagulation.
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Cetuximab
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Erbitux
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What is the mechanism of action of cetuximab?
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Monoclonal antibody to EGFR (epidermal growth factor receptor)
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What is the maximum infusion rate for cetuximab?
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10mg/min
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What are the adverse reactions caused by Erbitux?
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Infusion reactions (reduce rate)
Cardiopulmonary arrest Severe acneform rash Electrolyte abnormalities ( hypomagnesemia, hypocalcemia, hypokalemia) |
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What is the mechanism of action of erlotinib?
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Small molecule inhibitor which inhibits tyrosine kinase associated with EGFR.
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erlotinib
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Tarceva
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How is erlotinib eliminated?
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Hepatic metabolism and biliary excretion.
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What can you tell your patient in regards to the timing of the dose of erlotinib?
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Take one EMPTY stomach (1 hour before or 2 hours after eating)
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What are the adverse reactions associated with Tarceva?
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MI
Cerebrovascular accident Deep vein thrombosis Hepatotoxicity Diarrhea Skin reaction (rash) N/V |
