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alkylating agents DLT
myelosuppression (neutropenia)
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6 alkylating agents
- platinum agents
- alkyl sulfonates
- nitrogen mustards
- nitrosureas
- ethylenimines
- triazenes
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mesna dosing with ifosfamide
- 20% of ifosfamide dose immediately before and then 4 and 8 hours after IV boluses of IFOS
- mesna is 50% bioavailable - oral dose must be 40% of ifos dose
-
acrolein
metabolite of ifosfamide that irritates the bladder = hemorrhagic cystitis
-
nitrogen mustard DLT
hemorrhagic cystitis
-
nitrosureas DLT
DELAYED (possible a month later) myelosuppression
-
alkyl sulfonates toxicity
pulmonary
-
triazene that is IV only
dacarbazine - DTIC, Dome
-
triazene that is PO only
temozolomide - temoday, crosses BBB
-
triazene toxicity
severe N/V
-
cisplatin - platinol uniqueness
- platinum agent
- nephron & oto toxic - requires pre & post hydration
-
oxaliplatin - eloxatin unique
peripheral neuropathy that is cold activated
-
enzyme inhibitors
- anthracyclines
- epipodpphyllotoxins
- mitoxantrone
-
-
anthracycline uniqueness
- cardiotoxic - lifetime doses
- radiation recall - area radiated will turn bright red, even if several weeks later
- may discolor fluids red
-
epipodophyllotixins unique
IV infusion - dilute to < 0.4 mg/mL, concentration dependent, infuse over 30-60 minutes to avoid HoTN
-
mitoxantrone unique
- does NOT form oxygen free radicals = less damage to the heart
- urine may turn blue/green 24-48 hours after infusion
-
vinca alkaloids toxicity
- constipation
- vincristine - neuropathy in gut, big constipation compounded by antiemetics
-
vinca alkaloids uniqueness
- excreted via biliary route
- potent vesicants - apply heat & hyaluronidase
- vincristine max dose = 2 mg
-
taxane unique
- alopecia - lose ALL hair
- give taxane before platinums to decrease interaction
- abraxane - not substitutable
-
camptothecins DLT
- diarrhea
- over 50% have diarrhea on irinotecan
-
tx of early diarrhea
atropine - usually caused by cholinergics
-
tx of late diarrhea
- loperamide - 4 mg at first onset, then 2 mg every 2 hours until diarrhea free for 12 hours.
- overnight - 4 mg q 4 hours
-
folate antagonitst toxicities
- leukopenia
- tubular necrosis - hydration & alkalinization of the urine to prevent
- stomatitis - erosion down into the stomach and they can't eat
-
pemetrexed - alimta
- routine supplementation of folic acid and vitamin B12 = 1 week prior
- dosage adjustments based on CrCl - cutoff is 45 ml/min
-
leucovorin rescue dosing
- mtx 1-5 μM = 50mg/m2 IV q6h
- 5.01- 10 μM = 100mg/m2 IV q6h
- 10.1 - 20 μM = 200mg/m2 IV q6h
- rescue started app 12 hours after a 3-6 hour MTX infusion until MTX level is <0.1 μM
- must be initiated w/I 24 hours
-
pyrimidine analogues toxicities
- leukopenia
- flu-like syndrome
- rash
-
pyrimidine analogues causing cerebral toxicity (trouble walking) and chemical conjunctivitis
HD Ara-C - cerebral toxicity, trouble walking & chemical conjunctivitis (dexamethasone)
-
which pyrimidine analogue that can be a radio sensitizer
fluorouracil - 5FU
-
pyrimidine analogue associated with hand foot syndrome
- capecitabine - Xeloda
- oral prodrug of 5-FU
-
mesna dosing
- prevention is key - forced IV hydration (1-2 L of NS pre & post). oral 2-3 L/day
- 1st dose has to be IV
- 20% of ifos dose given IV prior to ifos dose then 40% of ifos dose PO at 2h & 6h
- or
- 20% of ifos dose given IV prior to ifos dose then
- 20% of ifos dose given IV at 4h & 8h
-
exudative diarrhea
disruption of intestinal epithelium, leakage of water, electrolytes, WBC's, RBC's
-
hypermotile diarrhea
rapid transit of stool, no time in the lumen for reabsorption
-
osmotic diarrhea
diminished absorption or excessive solutes which increase water entering the lumen, fasting will improve symptoms
-
secretory diarrhea
stimulation of active secretion above and beyond normal absorptive capacity, unaffected by fasting
-
biggest offenders of chemo induced diarrhea
- 5-fu
- methotrexate
- cytarabine
- irinotecan
-
loperamide dosing
4mg at first sign of diarrhea, then 2mg q 2h until diarrhea free for 12h
-
polymorphism putting pts on irinotecan at a higher risk for severe diarrhea
UGT1A1 7/7
-
drug responsible for EGFR and papulopustular rash, predominantly on the face
sorafenib - nexavar
-
drug responsible for EGFR affects from multiple kinase inhibitor presenting with a rash that predominantly affects the trunk
lapatinib - tykerb
-
2 reactions from multi-kinase inhibitors
- papulopustular rash
- hand-foot skin reaction
- paronychia
-
grade 1 HFSR and tx
- skin changes, erythema, edema, no pain
- tx = urea 20% BID + clobetasol 0.05% cream daily
-
grade 2 HFSR and Tx
- peeling, blisters, bleeding, +pain, limits ADL's
- tx urea 20% + clobetasol 0.05% cream daily + (NSAIDs/GABA agonists/narcotics)
-
grade 3 HFSR and tx
- severe changes, peeling, bleeding, +pain, limits self care ADLs
- tx - stop chemo tx until grade 0-1 toxicity, continue with clobetasol 0.05% cream BID & pain control (NSAIDs/GABA agonist/narcotics)
-
tx for high emetic risk
5HT3 antagonist + steroid + NK-1 antagonist
-
tx for moderate emetic risk
- day 1 - 5HT3 antagonist + steroid
- day 2-3 - 5HT3 monotherapy, steroid monotherapy, or NK1 + steroid, lorazepam, H2 blocker or PPI
-
tx's of low emetic risk
- dexamethasone
- metoclopramide
- prochlorperazine
- lorazepam
- H2 blocker or PPI
-
tx minimal emetic risk
no routine prophylaxix
-
tx of high to moderate risk nausea from oral chemo
- 5HT3 antagonist
- lorazepam
- H2 blocker or PPI
-
tx of low to minimal risk nausea from oral chemotherapy
PRN
-
antidote for extravasation of anthracyclines
- dexrazoxane - totect 1QD for 3d
- 1st dose ASAP w/I 6 hours after extravasation
- day 1 & 2 - 100mg/m2 (max 2000mg) IV over 1-2 hr
- day 3 - 500 mg/m2 (max 1000 mg) IV over 1-2h
- day 2 & 3 should be given w/I +/- 3 h of the time of 1st dose of subsequent days
- dose shold be reduced by 50% if CrCl<40ml/min
-
tx of extravasation of cisplatin & mechlorethamine
sodium thiosulfate
-
tx of extravasation of taxanes & vinca alkaloids
hyaluronidase
-
hyaluronidase dosing
- 150 units per mL in the hyaluronidase solution
- inject 1 mL of solution as (5) 0.2 mL injections into extravasation site
-
electrolyte disturbances that occur with tumor lyses syndrome
- hyper
- kalemia
- uricemia
- phosphatemia
hypocalcemia
-
criteria for a diagnosis of TLS
- 1 or more of the following
- ARF (rise in Scr to 1.5 x ULN)
- arrhythmias (including sudden cardiac death)
- seizures
-
laboratory diagnosis of TLS
- uric acid - > 8mg/dL
- potassium - > 6mEq/L
- phosphorus - > 6.5 mg/dL
- calcium - < 7 mg/dL
- or
- 25% increase from baseline of the above
2 or more lab changes must be observed w/I 3 days before or 7 days after cytotoxic therapy
-
prophylaxis tx for TLS
- allopurinol - 48hr prior to treatment
- 100 mg/m2 PO 1 8h (max = 800 mg)
-
2 points about allopurinol tx
- does not alter existing uric acid
- accumulation of xanthines can worsen renal fxn
-
tx of TLS
- rasburicase (elitek)
- converts uric acid into allantoin
- must be on ice immediately
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