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IOS6 exam 3
Chemo Toxicities (O'Bryant)
| Question | Answer |
|---|---|
| Toxicity grade not requiring dose adjustment | Grades 1-2 |
| Toxicity grade requiring held doses/reduced doses to try and prevent toxicity | Grades 3-4 |
| Most common acute dose-limiting side effect? | Myelosuppression (WBC [neutrophils], platelets, RBC). Mostly associated w/traditional cytotoxic agents. |
| Most common non-hematologic side effect? | N/V |
| Management options for hematologic toxicity | Hold and/or reduce doses (in metastatic patients), hematopoietic growth factors, transfusions ANC > 1500/mm^3; Platelets > 100,000/mm^3 |
| Most effect method for prevention of neutropenia? | colony stimulating factors |
| Most common method for treating thrombocytopenia? | platelet transfusion |
| Two options for the treatment of anemia? | RBC transfusions & erythropoietin stimulating agents (used to prevent transfusions). Tx with EPO is associated w/increased mortality, so only indicated for patients w/chemo induced anemia. Only indicated in patients w/metastatic disease. |
| Metabolite of cyclophosphamide and ifosfamide associated with bladder toxicity? | Acrolein: binds to thiols in bladder mucosa and produces bladder wall damage (hemorrhagic cystitis) |
| Risk factors for acrolein associated toxicities w/cyclophosphamide & ifosfamide? | high dose & cumulative dose, dehydration, pelvic XRT Symptoms: hematuria, dysuria, increased urine frequency |
| Prevention of bladder toxicity associated with cyclophosphamide? | Hydration! or Mesna (complexes w/acrolein to form a non-toxic compound that is voided) |
| Agents that are associated with cardiac toxicity? | Anthracyclines: Doxorubicin (greatest risk), Epirubicin, Idarubicin, Daunorubicin Toxicity is due to increase in free radical production that damages mitochondria and reduces energy production. |
| Why is the heart more susceptible to toxicity from anthracyclines? | Many mitochondria and low levels of antioxidant enzymes |
| Risk factors for anthracycline induced cardiac toxicity? | High cumulative doses, very young or old, female, pre-existing heart disease, genetics |
| "Speed limit" for anthracycline administration? | 550 mg/m^2 (absolute max) 350 mg/m^2 (max in children) 400 mg/m^2 (max with concurrent radiation) Give doses as a bolus to reduce toxicity! |
| Prevention of cardiac toxicity with anthracyclines... | Measure LVEF (hold if <45-50% or >10% drop) Limit cumulative doses Avoid high peaks (frequent small doses) Use less toxic analogs or liposomal products Pretreat w/dexrazoxane (begin @ 300mg/m^2) |
| Prevention and management of mucositis? | Dental evaluation, strict oral hygiene, symptomatic relief (local analgesics, protective agents, anti-infectives) Prevention w/Palifermin (keratinocyte growth factor) |
| Most common agents responsible for causing mucositis... | 5-FU, doxorubicin, MTX (really any cytotoxic agent can cause it) |
| Prevention of acute and chronic diarrhea... | Acute: prophylaxis and tx with atropine Chronic: aggressive loperamide dosing (don't follow box); octreotide for unresponsive diarrhea |
| Loperamide dosing for chemotherapy related diarrhea... | 4mg after 1st loose stool, then 2mg Q2H, stop if no BM in 12 hours, restart if diarrhea recurs |
| Chemo agents most likely to cause diarrhea? | 5-FU + leucovorin or 5-FU continuous infusion Irinotecan!! |
| Pathophysiology of hepatotoxicity with chemo agents | Covalent binding between reactive metabolite & liver cell proteins or DNA. Ca alterations may damage cell membranes. Usually an acute reaction that will recover during rest period. |
| Agents that commonly cause hepatotoxicity... | Cytarabine (high doses), MTX (chronic low doses), Capecitabine (bilirubin), I-Asparaginase (protein synthesis), antiandrogens (flutamide) |
| Most common agents associated w/infertility? | alkylating agents (affects spermatogenesis; may be reversible) & hormonal agents (androgen ablation; can also decrease libido) |
| Most common agent to cause nephrotoxicity? | Cisplatin: renal tubule poison (proximal tubules) |
| Prevention of nephrotoxicity associated with cisplatin... | Hydration, Mg & K supplementation, diuretics (be careful to avoid dehydration), amifostine (binds cisplatin; rarely used), carboplatin alternative (dosed using SCr) |
| Chemo agent that is nephrotoxic due to precipitation of crystals into renal tubules? | MTX (mostly with high dose regimens) Prevent by alkalinization of urine (pH>7), hydration |
| Treatment of neurotoxicity associated with chemo agents... | Hold/reduce dose, antiepileptic drugs (for peripheral neurophathies) |
| Agents that can cause neurotoxicity to the CNS | Cytarabine: high dose; cerebellar toxicity Ifosfamide: lethargy, somnolence, encephalopathy MTX: high dose; cerebellar toxicity, leukoencephalopathy |
| Agents that can cause neurotoxicity to the PNS | Cisplatin/Carboplatin: sensory with stocking-glove distribution; chronic & cumulative; ototoxicity; ocular Vincas: sensory & motor; autonomic; cranial (will KILL patient if given intrathecally) Taxanes: sensory & motor |
| What should patients on oxaliplatin avoid? | cold and ice neurotoxicity involving hyperexcitability from damage to Na channels |
| Agents likely to cause pulmonary toxicity... | Busulfan, bleomycin (most common), targeted therapies (HER1 inhibitors) Stop drug if this occurs!! |
| Max dose of bleomycin to reduce the risk of pulmonary toxicity... | Cumulative doses > 450 units; single dose > 30 units |
| Risk factors for pulmonary toxicity... | elderly, emphysema, XRT, high O2, renal failure, lymphoma |
| Agents with very high risk of causing alopecia | anthracyclines and taxanes (causes full body alopecia) |
| Agents that commonly cause rashes... | gemcitabine, small molecule tyrosin kinase inhibitors, EGFR inhibitors |
| Agents that cause photosensitivity... | 5-FU, vinblastine, dacarbazine, MTX |
| Agents that cause hand-foot syndrome | Capecitabine, 5-FU, liposomal anthracyclines |
| Vesicant drugs that can cause extravasation reactions (tissue breakdown)... | Anthracyclines (ice +/- dexrazoxane) Vincas (warm packs; hyaluronidase) Administer through central line or slow IV push |
| Drug that most commonly causes type 1 hypersensitivity reactions | Paclitaxel>>>docetaxel premedicate w/benadryl, dexamethasone, H2RA |
| Agents to avoid during pregnancy | MTX, antiandrogens, antiestrogens |
| Agent that can cause fluid retention and pulmonary edema? | Docetaxel (pretreat w/dexamethasone) |
| Agents responsible for secondary cancer... | Alkylating agents (most common; leukemia) TOPO inhibitors |
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