Chemo Flashcards
Topotecan DLT
Myelosuppression, esp thrombocytopenia. ANC>1500, Plt>100.
Topotecan MOA
Binds topoisomerase-I, stabilizes DNA complex preventing ligation resulting in single-strand breaks. S phase specific.
Topotecan dosing
Ovary: 4mg/m2 D1, D8, D15 q28d (preferred), or 1.25mg/m2 D1-5 q21d
Cervix: 0.75mg/m2 D1-3, q21d
30min infusion
Indications for dose adjustment of topotecan
Renal impairment (CrCl - urinary excretion)
Febrile neutropenia (esp. in combination with cisplatin)
Thrombocytopenia <25
Neutropenia <500
Diarrhea G3-4 (hold) –> Hypokalemia
Consider addition of GCSF
Discontinue for interstitial lung disease
Topotecan adverse effects
Fatigue, GI upset, myelosuppression, irritant*
Doxil (PLD) DLT
Palmar-plantar erythrodysesthesia (hand-foot syndrome)
Palmar-plantar erythrodysesthesia
Doxil/PLD. Avoid tight-fitting clothing. Use emollient. Dose-reduce with Grade 3 toxicity.
Doxil Box Warning
- Cardiomyopathy, assess EF before/during/after treatment.
2. Infusion reaction.
Definition of cardiotoxicity
> 20% change from baseline EF
Doxil MOA
Anthracycline, topoisomerase-II inhibitor. Intercalates with DNA, prevents ligation. Produces free radicals, cleave DNA and cell membrane. Non-cell cycle specific.
PLD vs doxorubicin
Liposomal pegylated form increases blood circulation time, less cardiotoxicity, better tolerated.
Doxil dosing
30, 40, or 50 mg/m2 q28d until disease progression or unacceptable toxicity (usually trial 4 cycles). 60min infusion.
Dose reduce if Serum Bilirubin: 1.2-3 (75%), >3 (50%). Hepatically cleared.
550mg/m2 max lifetime dose of doxorubicin.
Doxil adverse effects
PPE [Hand-foot syndrome] (DLT), myelosuppression (rare), stomatitis, nail discoloration, infusion reaction, fatigue, cardiomyopathy, hyperbilirubinemia, electrolyte disturbance (hyperCa, hypoK, hypoNa), irritant*
How to treat vesicant/irritant injury
Discontinue, aspirate extravasated solution, remove needle, APPLY ICE, elevate extremity
EXCEPT apply HEAT for vinca alkaloids, etoposide (cold worsens skin ulceration)
Renal Dose Adjustments
Bleomycin Carboplatin/Cisplatin Capecitabine Cyclophosphamide Methotrexate Mitomycin Premetrexid Topotecan Hydroxyurea Etoposide Gemzar
Hepatic Dose Adjustments
Taxol Adriamycin Doxil Vinka alkaloids Irinotecan 5FU
Drugs that Cross the Blood-Brain Barrier
Methotrexate 5FU Topotecan Temodar Niraparib (PARPi)
Fe toxicity
Bleomycin
Adriamycin
Doxil
Cardiotoxicity
Adriamycin Cyclophosphamide Herceptin (CHF) 5FU Mitomycin Taxol (bradycardia)
Palmar-plantar erythrodysesthesia (PPE)
Doxil 5FU Capecitabine Taxotere Sorafenib (tyrosine kinase inhibitor) Sunitinib (receptor tyrosine kinase inhibitor)
Pulmonary toxicity
Bleomycin Gemzar Methotrexate Immunotherapies Melphalin Mitomycin
Prodrugs
5FU Mitomycine Gemzar Ifosfamide Cyclophosphamide Irinotecan Capecitabine
Secondary malignancy
Melphalan Cyclophosphamide Etoposide (>2g lifetime) Platinums Ifosfamide
Vesicants
Vinka alkaloids Etoposide Cisplatin Adriamycin ActD Taxol
SIADH
Vinka alkaloids
Ifosfamide
Cyclophosphamide
Bleomycin DLT
Pulmonary toxicity
Cisplatin DLT
Nephrotoxicity, ototoxicity
Adriamycin DLT
Cardiotoxicity
Cyclophosphamide DLT
Myelodysplasia, nephrotoxicity
Methotrexate DLT
Stomatitis
Ifosfamide DLT
Nephrotoxic, treat with Mesna
Platinums DLT
Thrombocytopenia
Taxanes DLT
Neurotoxicity / neuropathy
Vinka alkaloids DLT
Neurotoxicity
Anastrazole DLT
Diarrhea
Irinotecan DLT
Diarrhea
5FU DLT
Myelodysplasia
Avastin DLT
HTN
Taxotere DLT
Edema
Carboplatin dosing
Total dose = AUC x (GFR+25) (calvert formula)
AUC = 5 usually
GFR = [(140-age)x0.85(wt in kg)] / [72 x SeCr] (cockgroft gault formula)
Cr must be >/= 0.7
Infuse over 30-60min
Carboplatin/Cisplatin MOA
Binds DNA forming crosslinks, denaturation of DNA helix
Carboplatin adverse effects
Myelosuppression (DLT, nadir day 7-10, Plt and ANC)
N/V/D, fatigue (~day 3)
Electrolyte disturbance (hypoMg, hypoK, hypoNa, hypoCa)
Hypersensitivity ** delayed, usually after 6 cycles
Cisplatin dosing
40mg/m2 q1wk with RT 70mg/m2 q21d *MUST calculated BSA each time *Pre and post hydration necessary *Long infusion (6hrs) at 1mg/min, can use mannitol to protect kidneys
Cisplatin adverse effects
Nephrotoxicity (DLT) - do not admin if Cr>1.5ish
Ototoxicity**
N/V (worse than carbo)
Myelosuppression (less than carbo)
Paclitaxel (Taxol) dosing
135-175mg/m2 q21d
80-65mg/m2 D1, 8, 15 q21d
BSA: cap at 2
Paclitaxel infusion instructions?
Administer BEFORE platinum (less myelosuppression)
3hr infusion: worse neuropathy
24hr infusion (old skool): worse myelosuppression (“bathes the bone”)
PRETREAT: steroids, antiemetic, H2 blocker, benadryl
Paclitaxel adverse effects
Neurotoxicty/neuropathy (DLT)
Myelosuppression (nadir day 10-14, Plt and ANC)
Alopecia**
Hypersensitivity** - to cremaphor
Taxol infusion reaction
Usually with first treatment
“Hot seat”, chest pain, back pain
Flushing, angioedema
Hypotension, dyspnea
*can re-challenge if not anaphylactic
Treating hypersensitivity reaction
- Stop infusion
- Evaluate, check VS
- Give benadryl, steroids, epi if needed
- Monitor 30-60min
- If symptoms resolve, can resume at slower rate
Neuropathy treatment
B6, gabapentin, amitryptaline, cymbalta
Treating chemo nausea
- Choose anti emetics from multiple classes, treat for D1-3 of cycle
Zofran, Aloxi, compazine, emend, ativan (good for anticipatory nausea, anxiolytic) - Dexamethasone 8mg q8h, D0-2 of cycle
Can cause mania, adrenal insufficiency (periop stress dose steroids), caution with DM, decrease dose if giving with Emend
Gemcitabine MOA
Pyrimidine analog, antimetabolite. Inhibits DNA synthesis by blocking DNA polymerase and RNA reductase. S phase.
Gemcitabine dosing
750-1000mg/m2 D1,8,15 q28d OR D1,8 q21d
Infuse over 30-60min (longer or more frequent infusions = more toxicity)
Use: recurrent ovary, sarcoma, recurrent cervix
Gemcitabine adverse effects
Myelosuppression (DLT - nadir 10-14d, ANC and Plt) Hepatotoxic - monitor bilirubin Radiation recall** Gem fever** N/V/D, stomatitis, flu-like symptoms GU: hematuria, proteinuria Rare: PRES, HUS, RDS
Abraxane (nab-paclitaxel) dosing
260mg/m2 q21d (ovary) 100mg/m2 D1,8,15 q28d (ovary) 125mg/m2 D1,8,15 q28d (cervix) Infuse over 30-40min (shorter = less HS rxn) *Bovine product - albumin bound
Abraxane adverse effects
Neutropenia (DLT) Myalgia, arthralgia Alopecia, rash Neuropathy, ocular disturbance N/V/D, electrolyte disturbance (hypoK)
Abraxane MOA
stabilizes microtubules, mitotic disruption in G2 phase
Paclitaxel MOA
mitotic spindle poison, stabilizes microtubules
Paclitaxel extravasation antidote
hyaluronidase
Docetaxel (Taxotere) dosing
60-75mg/m2 q21d
35mg/m2 D1,8,15 q21d
Infuse over 1hr
Premedicate: steroids D0-2 to decrease HS and edema
Docetaxel adverse effects
Edema/fluid retention (DLT) Myelosuppresion (DLT, ANC nadir 7d) Alopecia, skin/nail discoloration Hypersensitivity Hypotension Cardiac tamponade, pleural effusion Stomatitis ***NOT neuropathy - use for preexisting***
Adriamycin (doxorubicin) box warning
Cardiomyopathy, extravasation related skin necrosis, secondary malignancy, myelosuppression
Adriamycin dosing
40-60mg/m2 q21d MAX LIFETIME DOSE 450-550mg/m2 Adjust for bilirubin Admin: central line infusion, or IV push over 3-10min. Give before platinum if in combo. DO NOT give with Herceptin (cardiotox).
Adriamycin adverse effects
Cardiotoxicity (DLT - monitor EF) Vesicant - antidote: DMSO, dexrazoxane Fatigue, malaise Mod-high emetogenic (pretreat) Myelosuppression (nadir 10-14d)
Adriamycin MOA
Inhibits DNA/RNA synthesis, intercalates with Topoisomerase-II causing fragmentation. Also causes free radicals.
Minimum approximate EF for administration of Adriamycin?
> /=50%
What are the byproducts of ifosfamide and how do you manage the effects?
Chloroacetaldehyde - can cause encephalopathy, treat with methylene blue
Acrolein - causes hemorrhagic cystitis; administer ifos with mesna and hydration
What are the two forms of doxorubicin, and what cancer are they used for?
Doxil (pegylated liposomal) - ovary
Adriamycin - carcinosarcoma/uterus
What are the pros/cons of taxotere vs abraxane? Why would you use them instead of taxol?
Both can be used for taxol reaction as they do not contain crempahor.
Taxotere: less neuropathy, but associated with severe edema, requiring pretreatment with steroids (caution in diabetics)
Abraxane: not associated with significant edema
What is the reaction to in a taxol chemo reaction?
Cremaphor