Intercalators, Tubulin actin, Topo I-II

Camptotethecin analogues list and MOA

Topotecan, Irinotecan

Topoisomerase I inhibitors

Epipodophyllotoxins list and MOA

Etoposide, Teniposide

Forms complex with topoisomerase II & DNA, prevents DNA resealing, leads to successive DNA breaks and cell death

Vinca Alkaloids list and MOA

Vincristine, Vinblastine, Vinorelbine

Bind tubulin, blocking its association with alpha tubulin arresting mitotsis in metaphase

Taxanes list and MOA

Paclitaxel, Docetaxel

Bind beta tubulin to promote and stabilize microtubule formation, thus halting mitosis in metaphase

Anthracyclines and Anthracenediones list and MOA

Doxorubicin, Daunorubicin, Idarubicin, Liposomal Doxorubicin Mitoxantrone

1) Intercalates DNA, preventing transcription and replication
2) Inhibits Topo II
3) Generation of free radicals via iron interaction

Bleomycin MOA

Causesw oxidative damage to nucelotides leading to DNA strand breaks

Dose limiting adcerse effect of anthracyclines

Cardiotoxicity

• Dexrazoxane may be used in certain circumstances to reduce risk

Relative neurotoxicities of the tubulin-active agents

Tingling, burning, numbness in fingers and does- worse with vincristine

What route should you never give vincristine

Intrathecally

What is the dose limiting class toxicty of taxanes

Myelosuppresion

What is the dose limiting class toxicty of irinotecan

Diarrhea

Etopside toxicities

Infusion related: hypotension & bronchospasm
Treatment related secondary leukemia
myrelosuppresion
Precepitiation in solution
(Low emetogenicity)

What is the dose limiting toxicity of bleomycin

Pulmonary

What drugs have maximum lifetime doses

Bleomycin
Daunorubicine
Doxorubicin
Epirubicin
Idarubicin
Mitoxantrone
Vincristine (2mg cap bc neurotoxicity)

How is are camptothecin analogs metabolized

Topotecan- renal
Irinotecan (pro drug)- Activated via carboxyesterases, Inactivated by CYP3A4 and UGT

Which meds need renal dose adjustments

Etoposide
Bleomycin

Which meds need hepatic dose adjsutments

Vincaalkoids
Taxanes
Antracyclines & Anthracenedione

Chemotherapy extravasation management

1) Stop infusion

2) Apply heat (vincas) or cold (anthracyclines)

3) Administer antidote

• Anthracyclines: Dexrazoxane

• Vincas: Hyaluronidase

Paclitaxel vs Docetaxel hypersensitivity prophylaxis

Paclitaxel	Docetaxel
Dexamethasone Famotidine Diphenhydramine	Dexamethasone

Treatment of acute and delayed ironotecan associated diarrhea

Acute	Delayed
Atropine	Loperamide Lomotil second line

Treatment of chemo induce neuropathy for paclitaxel

1) Duloxetine (preferred)

2) Gabapentin

What factors increase the risk of cardiomyopathy in patients receiving anthracyclines?

Cumulative anthracycline dose
Cardiac involvement in the radiation field
Older

What factors increase the risk of bleomycin pulmonary toxicity?

Exposure to high FiO2
Preexisting lung disease
>70 years
Larger doses (>30 units)
Cumulative dose >400 units
Lung field radiation therapy