Chemotherapy Part III - Vinca, Taxane, Topo I, Platinum Analogs, Alkylating Agents

Anti-microtubule drug classes

- vinca alkaloids = inhibit assembly

- taxanes = inhibit disassembly

Vinca alkaloids block what phase

- M phase

Vinca alkaloids metabolized by

- liver = need hepatic adjustment for dose

Vinca alkaloids DDI

Get VINCA (Limca) in PB (Punjab)

- phenytoin

- bleomycin

Vinca alkaloids + bleomycin causes risk of

V + B = R

- Raynaud's syndrome

Vinca alkaloids administration

Vin Diesel = FAST

- infuse as a rapid push to avoid extravasation

Vinca alkaloids SE

- Very constipated

- hypertension

***Vin diesel has hypertension

Oncovin (name)

- vincristine

Vincristine DDI

PDF

- phenytoin

- digoxin

- filgrastim

Vincristine CI

- pregnancy

Which drugs cause the least myelosuppression?

bleoMYcin + vincRIStine = MYelosuppRISsion

- vincristine

- bleomycin

Paclitaxel is given w/ what? What can it cause? What do you do because of it?

- Cremphor EL vehicle (castor oil)

- severe HYPERSENSITIVITY rxn

- premedicate w/ antihistamine, corticosteroid, etc

Paclitaxel preparation caution

Paclitaxel = Pvc

- PVC containers

Paclitaxel w/ platinum analog (carboplatin/cisplatin), which goes first?

PC

- paclitaxel before cisplatin/carboplatin

***PACLITAXEL IS ALWAYS GIVEN FIRST

Taxotere (name, formulated in, storage)

Docetaxel

- formulated in polysorbate 80

- use only glass

***docetaxel = polysorbate = glass

Topoisomerase I drugs and is given in

- irinotecan

- topotecan

topoDecan or irinoDecan

- D5W

Camptosar (name, active metabolite)

iriNe is 38

- irinotecan = pro-drug

- SN-38 = metabolized through the liver

Irinotecan is associated with what mutation and with what other drug?

- UGT1A1 mutation = enhance toxicity/accumulation

w/ 5-FU

***5F-UgtIa1

Irinotecan SE, timeframe, treatment

Diarrhea

- < 24 hours = acute; treat w/ atropine

- > 24 hours = treat w/ imodium

Anthracycline drugs

DDIE

- doxorubicin

- daunorubicin

- idarubicin

- epirubicin

- mitoxantrone

Adriamycin (name)

- doxorubicin

Anthracyclines generate

- free radicals = superoxide anion radicals (OH)

Anthracyclines interact w/

- topoisomerase ii = NON CELL-CYCLE SPECIFIC

Doxorubicin SE

- cardiotoxicity

- red urine for 1-2 days after drug admin

- vesicant = extravasation

Mitoxantrone SE

- blue urine

Which anthracyclines have less cardiotoxicity?

- DaunoXome

- Doxil

***liposomal/pegylated daunorubicin

Doxorubicin administration

- infuse slowly over a long period of time

Rescue medication of doxorubicin (name, formulation)

- Dexrazoxane (Zinecard)

- IV

- iron-chelating

Dexrazoxane indication and dosing

Dex = 3 letters

- total of 300mg/m2 of doxorubicin

- 30 minutes before doxorubicin

- 10:1 dexrazoxane:doxor

Dexrazoxane is not recommended for

- START of doxorubicin therapy

- ADJUVANT therapy of breast cancer

Doxorubicin DDI

- heparin

- cyclophosphamide

- dexamethasone

Decrease cardiotoxicity of doxorubicin methods

- liposomal formulations

- use dexrazoxane

- prolong infusion time

Major cardiotoxicity dose for doxorubicin

D = 500

- 450 mg/m2

Mitoxantrone lifetime cumulative dose

M = 1000

- 140 mg/m2

Which drug has activation in hypoxic conditions?

- mitomycin

Mitomycin can cause what

heMo ureMic syndroMe = Mitomycin

- hemolytic-uremic syndrome = blood in urine

Dactinomycin toxicity

- hyperpigmentation

Bleomycin cannot be reconstituted in

- dextrose-containing solution

Bleomycin cumulative dose that can cause pulmonary toxicity

bleo = 4 letters

- 400 units

Etoposide PO to IV dose

- PO = 50% decrease

- IV = double PO dose

Which drugs cause cardiac toxicity?

- anthracyclines (doxorubicin)

- mitoxantrone

Which drugs cause diarrhea?

i-5:

- irinotecan

- 5-FU

Which drugs cause extravasation?

AMMVP

- anthracyclines

- mitomycin

- mechlorethamine

- vinca alkaloids

- paclitaxel

Which drugs cause hemorrhagic cystitis?

hemorrhagIC

- ifosfamide

- cyclophosphamide

Which drugs cause hypersensitivity?

PPT

- paclitaxel

- platinum analog

- topo II (etoposide, teniposide)

Which drugs cause pulmonary toxicity?

- bleomycin

- busulfan

***busulfan lung

Which drugs have minimal myelosuppression?

BV:

- bleomycin

- vincristine

Which drugs cause neurotoxicity?

Anti-microtubules:

- taxanes

- vinca alkaloids (vincristine more than vinblastine)

- platinum analogs

- methotrexate

Which drugs cause edema?

- docetaxel

Which drugs cause renal toxicity?

- cisplatin

- ifosfamide

- methotrexate

Platinum analog SE and which has less, which has more

- renal toxicity (cisplatin is worst than carboplatin)

- neurotoxicity (oxaliplatin is the worst)

Platinum analog moa

Platinum = 8 letters ~ 7

- cross-link at the N-7 position

Cisplatin produces severe ______ and is given with

- severe renal toxicity

- given w/ hydration and osmotic diuretic (mannitol)

What do you have to watch out with for oxaliplatin?

- COLD

Cisplatin SE

1st generation

- nephrotoxicity

- OTOTOXICITY

- N/V

Carboplatin SE

2nd generation

- less nephrotoxic

- worst myelosuppression

Cisplatin drug preparation

- DO NOT MIX WITH dextrose

Cisplatin DDI

- phenytoin

Cyclophosphamide rescue medication

- mesna

Cisplatin rescue medication

cisplaTIN = amifosTINe

- amifostine

If patient has poor renal function but still needs a platinum analog, which do you give?

- carboplatin

Cisplatin avoid

- aluminum needles

- alkaline solutions containing sodium bicarbonate

Amifostine SE

amiPOstine = hyPO

- hypotension

Carboplatin dose calculation (Total dose)

- Target AUC x (GFR + 25)

Do you need to give IV hydration for carboplatin?

- NO, less renal toxicity

Oxaliplatin SE

- neurotoxicity

- triggered by COLD

Oxaliplatin drug prep

- never use NS or any sodium containing solutions

Cytoxan name, SE, active metabolite that causes SE and rescue agent

- cyclophosphamide

- hemorrhagic cystitis

- acrolein

- mesna

Which drug has the worst extravasation?

- mechlorethamine

Which drug wipes out the bone marrow?

- melphalan

Which drug is the worst vesicant?

- mechlorethamine

Which drug causes pulmonary toxicity?

- busulfan

- bleomycin

Which drug class works through covalent bonding?

covALkylating bond

- alkylating agents

Alkylating agents subtypes

- nitrogen mustards

- nitrosureas

Alkylating agents can cause

- secondary tumors/malignancies

What do you do to reduce the risk of hemorrhagic cystitis with cyclophosphamide?

- fluid intake

- empty bladder several times daily

Which drug is prepackaged with mesna?

- ifosfamide

BCNU (drug, formulation, info)

- carmustine

- lipophilic/crosses the BBB

- Gliadel = drug-impregnated biodegradable water

Which drug is given for glioblastoma multiforme?

- Gliadel