Chemotherapy - Block 4 Flashcards
Define dose limiting toxicity?
A toxicity that may lead to a dosage decrease, tx delay, or discontinuation
Is hair loss a DLT?
No
Factors that contribute to dosage adjustment?
- Patient hx
- Cure vs prolongation of life
- Renal and hepatic dysfunction
MOA of antimetabolites??
Mimic nucleotides that disrupt replication and cell division
What are the classes of antimetabolites?
- Pyrimidine analogs
- Purine analogs
- Folate antagonists
What are the class toxicities for antimetabolites?
- Myelosuppression
- Diarrhea
What are the types of pyrimidine analogs?
- 5FU
- Capecitabine
- Cytarabine
- Gemcitabine
DLT for 5-FU?
- Stomatitis
- Myelosuppression
- Diarrhea
- Hand foot syndrome
DLT for capecitabine?
- Diarrhea
- Hand foot syndrome
What drug enhances activity and toxicity of 5-FU?
Leucovorin
What patient factor contributes to increased toxicity of pyrimidine analogs?
DPD deficiency
DDI of pyrimidine analog
Warfarin
DLT of cytarabine?
- Leukopenia
- Thrombocytopenia
What drug is sometimes given with allopurinol to prevent TLS?
6-MP (dose must be decreased to avoid toxicity)
DLT of methotrexate?
- Myelosuppression
- Mucositis and diarrhea
DLT of pemetrexed?
Neutropenia
What medication is given for methotrexate tox?
Leucovorin
What is the reversal agent for methotrexate nephrotoxicity?
Glucarpidase
Counseling for pemetrexed administration?
Give folic acid, B12, and dexamethasone
Examples of folate antagonists?
- Methotrexate
- Pemetrexed
What is the class toxicity for microtubule-targeting agents?
Peripheral neuropathy
What are the types of taxanes?
Paclitaxel (Taxol)
Paclitaxel NAB (Abraxane)
Docetaxel (Taxotere)
DLT of paclitaxel?
PN
DLT of paclitaxel NAB?
Myelosuppression
Which of the taxanes require pre-medication to avoid hypersensitivity?
Paclitaxel (diphenhydramine, steroid, H2RA)
Docetaxel (steroids prior to admin)
Are paclitaxel and paclitaxel NAB dosages interchangable?
No
What patient population requires taxane dosage adjustments?
Hepatic impairment
Type of epothilones? DLT?
Ixabepilone: PN and leukopenia
Example of non taxane microtubule inhibitors? DLT?
Eribulin: neutropenia
What do you give to pre-medicate when using ixabepilone?
Benadryl, H2RA, dexamethasone (if had previous rx)
Metabolism of ixabepilone?
CYP3A4
What are the types of vinca alkaloids?
- Vincristine
- Vinorelbine
- Vinblastine
What is the max dose of vincrisitne?
2 mg/dose
How should vinca alkaloids be administered?
Potent vesicant: apply heat id extravastion occurs
No IT admins: deliver in IVPB not syringe
DLT of vincrisitne?
Severe PN
DLT of vinorelbine?
Myelosuppression
DLT of vinblastine?
Myelosuppression
What are the topoisomerase I inhibiotrs?
- Irinotecan
- Irinotecan liposomal
ADRs of irinotecan? Which one is DLT? How do you treat it?
Acute diarrhea (12-24H): Atropine
Delayed diarrhea (DLT), >12-24H after dose: Loperamide
What mutation increases the toxcity of irinotecan?
UGT1A1
What are the topoisomerase II inhibitors?
- Etoposide
- Teniposide
DLT of etoposide?
Myelosuppression
DLT of teniposide?
Myelosuppression
Infusion instructions for topoisomerase II inhibitors?
Infuse over at least 30-6 min due to risk of hypotension
What is the MOA of antracycline?
- Intercalation in DNA
- Topoisomerase II inhibitor
ADR of antracyclines? Which ones are DLTs?
- Red urine
- Potent vesicants: apply ice and Totect (dexrazoxane)
- Delayed cardiomyopathy (DLT)
- Myelosuppression (DLT)
Types of antacyclines?
- Doxorubicin
- Daunorubicin
- Idarubicin
- Epirubacin?
Considerations prior to antracycline admin?
Must get baseline LVEF, LVEF should be >50% to be administered
Max dose for doxorubicin?
450-550 mg/m2
Max dose for daunorubicin?
550 mg/m2
Max dose for idarubicin?
150 mg/m2
Max dose for epirubicin?
900 mg/m2
How do you calculate lifetime dose?
[Select dose of drug in mg/m2/cycle] x [total number of cycles received] = cumulative doxorubicin dose in mg/m2
Types of antracenedione?
Mitoxantrone
ADR of mitoxantrone?
Cardiotoxicity (DLT)
Blue urine, fingernails, sclera
Max dose for mitoxantrone?
140 mg/m2
ADRs of busulfan?
- Pulmonary fibrosis
- N/V
- Seizure prophylaxis with stem cell transplant
Types of platinum agents?
- Cisplatin
- Carboplatin
- Oxaliplatin
ADR of cisplatin?
- N/V (100% with pretreatment)
- Nephrotoxicity
- Ototoxicity
Max dose for cisplatin?
100 mg/m2/cycle
What is the most emetic chemo agent?
Cisplatin
What are the steps required for administerating cisplatin?
- Hydration with NS required
- Supplement with K and Mg due to wasting
- Baseline hearing and after each dose
- Delayed hypersensitivity
ADRs of carboplatin?
- Myelosuppression
- NV
- Less PN, ototoxicity, and nephrotoxicity than cisplatin
How is carboplatin dosed?
Dosed based on AUC using Calvert formula
ADR of oxaliplatin?
PN (DLT) in >50% of patients
Acute <14 days: reversible exacerbated by cold
Persistant >14 days: may be permanent
Calvert formula?
Dose = (CrCl + 25) x AUC
How should nitrogen mustards be dosed?
Hydrate and frequent urination to prevent pain, hematuria, urgency
Cyclophosphamide: may use mesna for high doses
Ifosfamide: alwasy use mesna
ADRs of nitrogen mustards?
Hemorrhagic cystitis
NV
Alopecia
How should you administer mesna?
- Give IV liqud with juice, chocolate milk to mask taste
- If patient vomits within 2 hrs of taking PO mesna should recieve an additional PO or IV dose
- IV can be cmpounded to be given as PO solution
- PO form is difficult to tolerate
ADR of bendamustine?
- SJS
- TENS
- rash
- Tumor lysis (administer with allopurinol)
ADR of nitroureas?
Pulmonary toxicity
Myelosuppression
Facial flushing
How is carmustine used?
IV and biogradable wafers are implanted to residual tissue after surgical resection
How is lomustine administered?
For PO, don’t administer more than one dose at a time due to risk for fatal tox and OD
* Taken every 6 weeks
* Readily crosses BBB
ADR of procarbazine?
- Disulfirum like rx with alcohol
- Myelosuppression
- Neurotoxicity and neuropathy
How should procarbazine be adminsitered? DDI?
- Adminsiter on empty stomach
- Tyramine free diet due to MOAI
DDI: SSRI, TCAs
What is the max lifetime dose for bleomycin?
400 units
* Must receive test dose prior to actual infusion
ADR of bleomycin?
- Pulmonary fibrosis
- Anaphylaxis
- Hypersensitivity rx
ADR for arsenic?
- Differentiation syndrome (corticosteroids)
- Electrolyte abs (hype/hyper K, hypomag)
- QT prolongation
How do you administer arsenic?
Treat with dexamethasone 10 mg IV BID to resolve s/s
What is the first line for APL?
tretinoin
ADR of tretinoin?
- Retinoic acid syndrome-treat with corticosteroids
- QT prolongation
ADR of coricosteroids?
Insomnia
Fluid retention
Nausea
Increased appetite
Hyperglycemia
Prednisone or dexamethasone
Counseling on how to take corticosteroids?
- Take in am to avoid insomnia
- Take with food to avoid nausea
- Check glucose levels in diabetics
How do you calculate BSA?