08b Major Organ Toxicities (Enzyme and Microtubule Inhibitors) Lee

Question 1

Which cancer drugs require renal dose adjustments?

Answer 1

MTX. Cisplatin. Carboplatin. Cyclophosphamide. Bleomycin. Etoposide

Question 2

Which cancer drugs require hepatic dose adjustments?

Answer 2

Vinca alkaloids. Taxanes. Anthracyclines. Gemcitabine. Irinotecan. Etoposide (renal as well)

Question 3

What are the common toxicities associated with Enzyme Inhibitors?

Answer 3

Myelosuppression (DLT), N/V (except bleomycin), mucositis, alopecia

Question 4

Which Enzyme Inhibitors have cardiac effects?

Answer 4

Anthracyclines (Daunorubicin. Doxorubin. Idarubicin)

Question 5

Which Enzyme Inhibitors have pulmonary effects?

Answer 5

Bleomycin, Mitomycin

Question 6

Which Enzyme Inhibitors have Vesicant effects (induces blistering)?

Answer 6

Doxorubicin

Question 7

What are the ADRs when Anthracyclines are used for Bladder Instillation?

Answer 7

Irritable bladder symptoms, blood in urine, loss of bladder control, painful urination, strong urge to urinate

Question 8

What are the risk factors for Cardiomyopathy caused by Anthracyclines?

Answer 8

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)

Question 9

What are the results of Doxorubicin-Associated Cardiomyopathy?

Answer 9

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)

Question 10

What dose of Doxorubicin do you NOT want to exceed d/t much higher incidence of CHF?

Answer 10

550mg/m2 total dose

Question 11

What is the MOA of cardiotoxicity caused by Anthracyclines?

Answer 11

Iron-dependent O2 free-radical formation: anthracycline-iron-O2 complex –> initiate lipid peroxidation –> damage mitochondrial DNA, gradual loss of myofibrils and decreased contractility

Question 12

How is max dosing of Doxorubicin like for prevention of cardiomyopathy?

Answer 12

< 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)

Question 13

What is Dexrazoxane (Zinecard, Totect)?

Answer 13

Iron chelator, blocks generation of Fe-doxorubicin complex

Question 14

What are the uses of Dexrazoxane (Zinecard, Totect)?

Answer 14

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)

Question 15

How is Dexrazoxane dosed?

Answer 15

Dexrazoxaine:Doxorubicin 10:1, IV over < 15 minutes, within 30 minutes of Doxorubicin

Question 16

Which agents are associated with Pulmonary Toxicity through hypersensitivity reaction?

Answer 16

Sudden onset, not-dose related, eosinophils: Bleomycin

Question 17

Which agents are associated with Pulmonary Toxicity through Direct Injury To Lung (Fibrosis)?

Answer 17

Bleomycin!!! Carmustine, Cyclophosphamide, Busulfan (Busulfan Lung), Chlorambucil

Question 18

What is the MOA of Bleomycin Lung Fibrosis?

Answer 18

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

Question 19

What is Bleomycin inactivated by?

Answer 19

Aminohydrolases (which is low in skin and lungs)

Question 20

At what Bleomycin dose is pulmonary toxicity a concern?

Answer 20

Bleomycin cumulative dose > 400 units or > 200 units/m2

Question 21

What is prevention like for pulmonary toxicity caused by Bleomycin?

Answer 21

No O2 treatment if risk of fibrosis (“No O2, Bleo Patient”). Limit cumulative dose

Question 22

What is treatment like for pulmonary toxicity caused by Bleomycin?

Answer 22

None. Often irreversible, progressive. Steroids helpful if hypersensitivity-related

Question 23

What is the primary toxicity related to Taxanes (Paclitaxel, Docetaxel)?

Answer 23

Neutropenia. Neurotoxicity - DLT (similar to platinum-induced)

Question 24

What is hypersensitivity like with Paclitaxel?

Answer 24

~40% of patients. Cause: Cremophor EL vehicle (castor oil)

Question 25

What is used to treat Paclitaxel hypersensitivity?

Answer 25

H1, H2, and corticosteroids (mnemonic “ABCD”): Antiemetic, Benadryl, Cimetidine (any H2 blocker), and Dexamethasone

Question 26

What is a unique toxicity related to Taxotere (Docetaxel)?

Answer 26

Pleural effusion, fluid retention. Pre-medicate: Dexamethasone 8mg PO BID x3 days, starting 1 day prior to treatment

Question 27

What is the BBW for Rituximab?

Answer 27

Infusion-Related Reaction: Hypotension, bronchospasm, MI, arrythmias. Can pre-medicate with Benadryl, Famotidine, Dexamethasone

Question 28

How should Etoposide (TOP II Inhibitor) be administered?

Answer 28

Infuse at least over 60 minutes. RX prep: Concentration-dependent stability

Question 29

What is the dose limiting ADR for Irinotecan (TOP I Inhibitor)?

Answer 29

Diarrhea. Treat early diarrhea w/ anticholinergics (atropine). Late diarrhea w/ Loperamide

Question 30

Which agent can cause extreme Extravasation (skin wasting) and tissue necrosis?

Answer 30

Doxorubicin

Question 31

What is the management of Extravasation with Anthracycline use?

Answer 31

Local antidote: Dexrazoxane (Totect). Cold compresses

Question 32

What is the management of Extravasation with Vinca Alkaloid use?

Answer 32

Hyaluronidase. Warm compresses