Flashcards in 08b Major Organ Toxicities (Enzyme and Microtubule Inhibitors) Lee Deck (32):
Which cancer drugs require renal dose adjustments?
MTX. Cisplatin. Carboplatin. Cyclophosphamide. Bleomycin. Etoposide
Which cancer drugs require hepatic dose adjustments?
Vinca alkaloids. Taxanes. Anthracyclines. Gemcitabine. Irinotecan. Etoposide (renal as well)
What are the common toxicities associated with Enzyme Inhibitors?
Myelosuppression (DLT), N/V (except bleomycin), mucositis, alopecia
Which Enzyme Inhibitors have cardiac effects?
Anthracyclines (Daunorubicin. Doxorubin. Idarubicin)
Which Enzyme Inhibitors have pulmonary effects?
Which Enzyme Inhibitors have Vesicant effects (induces blistering)?
What are the ADRs when Anthracyclines are used for Bladder Instillation?
Irritable bladder symptoms, blood in urine, loss of bladder control, painful urination, strong urge to urinate
What are the risk factors for Cardiomyopathy caused by Anthracyclines?
Age > 65 or in pediatrics. Pre-existing cardiac disease. RT to chest wall. Chemotherapy-specific (large bolus dose; cumulative lifetime doses; combination w/ other cardiotoxins)
What are the results of Doxorubicin-Associated Cardiomyopathy?
Arrythmias (non-dose-related). Subacute - days to weeks. CHF (Chronic effect) - late onset (months to years after receiving anthracyclines, related to cumulative doses, common/life threatening/irreversible)
What dose of Doxorubicin do you NOT want to exceed d/t much higher incidence of CHF?
550mg/m2 total dose
What is the MOA of cardiotoxicity caused by Anthracyclines?
Iron-dependent O2 free-radical formation: anthracycline-iron-O2 complex --> initiate lipid peroxidation --> damage mitochondrial DNA, gradual loss of myofibrils and decreased contractility
How is max dosing of Doxorubicin like for prevention of cardiomyopathy?
< 500-550 mg/m2 if low risk. < 400-450 mg/m2 if high risk. Slow infusion > 6 hrs or smaller weekly dose. Combination with cardioprotectant (Iron chelator dexrazoxane)
What is Dexrazoxane (Zinecard, Totect)?
Iron chelator, blocks generation of Fe-doxorubicin complex
What are the uses of Dexrazoxane (Zinecard, Totect)?
1) Metastatic breast cancer, received Doxorubicin > 300mg/m2 and will likely continue. 2) Use with other anthracyclines or at risk for cardiac dysfunction. 3) Extravasation (skin damage) from anthracyclines (use Totect only)
How is Dexrazoxane dosed?
Dexrazoxaine:Doxorubicin 10:1, IV over < 15 minutes, within 30 minutes of Doxorubicin
Which agents are associated with Pulmonary Toxicity through hypersensitivity reaction?
Sudden onset, not-dose related, eosinophils: Bleomycin
Which agents are associated with Pulmonary Toxicity through Direct Injury To Lung (Fibrosis)?
Bleomycin!!! Carmustine, Cyclophosphamide, Busulfan (Busulfan Lung), Chlorambucil
What is the MOA of Bleomycin Lung Fibrosis?
Bleomycin --> Breaks in DNA by an oxidative process via free radical formation. Damage to pulmonary endothelial cells and type I pneumocytes --> Inflammatory exudate within alveoli and fibrosis that may permanently impair diffusion and decrease lung volumes
What is Bleomycin inactivated by?
Aminohydrolases (which is low in skin and lungs)
At what Bleomycin dose is pulmonary toxicity a concern?
Bleomycin cumulative dose > 400 units or > 200 units/m2
What is prevention like for pulmonary toxicity caused by Bleomycin?
No O2 treatment if risk of fibrosis ("No O2, Bleo Patient"). Limit cumulative dose
What is treatment like for pulmonary toxicity caused by Bleomycin?
None. Often irreversible, progressive. Steroids helpful if hypersensitivity-related
What is the primary toxicity related to Taxanes (Paclitaxel, Docetaxel)?
Neutropenia. Neurotoxicity - DLT (similar to platinum-induced)
What is hypersensitivity like with Paclitaxel?
~40% of patients. Cause: Cremophor EL vehicle (castor oil)
What is used to treat Paclitaxel hypersensitivity?
H1, H2, and corticosteroids (mnemonic "ABCD"): Antiemetic, Benadryl, Cimetidine (any H2 blocker), and Dexamethasone
What is a unique toxicity related to Taxotere (Docetaxel)?
Pleural effusion, fluid retention. Pre-medicate: Dexamethasone 8mg PO BID x3 days, starting 1 day prior to treatment
What is the BBW for Rituximab?
Infusion-Related Reaction: Hypotension, bronchospasm, MI, arrythmias. Can pre-medicate with Benadryl, Famotidine, Dexamethasone
How should Etoposide (TOP II Inhibitor) be administered?
Infuse at least over 60 minutes. RX prep: Concentration-dependent stability
What is the dose limiting ADR for Irinotecan (TOP I Inhibitor)?
Diarrhea. Treat early diarrhea w/ anticholinergics (atropine). Late diarrhea w/ Loperamide
Which agent can cause extreme Extravasation (skin wasting) and tissue necrosis?
What is the management of Extravasation with Anthracycline use?
Local antidote: Dexrazoxane (Totect). Cold compresses