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Fellows 2021! > Chemo > Flashcards

Chemo Flashcards

1
Q

Topotecan DLT

A

Myelosuppression, esp thrombocytopenia. ANC>1500, Plt>100.

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2
Q

Topotecan MOA

A

Binds topoisomerase-I, stabilizes DNA complex preventing ligation resulting in single-strand breaks. S phase specific.

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3
Q

Topotecan dosing

A

Ovary: 4mg/m2 D1, D8, D15 q28d (preferred), or 1.25mg/m2 D1-5 q21d
Cervix: 0.75mg/m2 D1-3, q21d
30min infusion

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4
Q

Indications for dose adjustment of topotecan

A

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

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5
Q

Topotecan adverse effects

A

Fatigue, GI upset, myelosuppression, irritant*

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6
Q

Doxil (PLD) DLT

A

Palmar-plantar erythrodysesthesia (hand-foot syndrome)

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7
Q

Palmar-plantar erythrodysesthesia

A

Doxil/PLD. Avoid tight-fitting clothing. Use emollient. Dose-reduce with Grade 3 toxicity.

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8
Q

Doxil Box Warning

A
  1. Cardiomyopathy, assess EF before/during/after treatment.

2. Infusion reaction.

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9
Q

Definition of cardiotoxicity

A

> 20% change from baseline EF

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10
Q

Doxil MOA

A

Anthracycline, topoisomerase-II inhibitor. Intercalates with DNA, prevents ligation. Produces free radicals, cleave DNA and cell membrane. Non-cell cycle specific.

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11
Q

PLD vs doxorubicin

A

Liposomal pegylated form increases blood circulation time, less cardiotoxicity, better tolerated.

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12
Q

Doxil dosing

A

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.

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13
Q

Doxil adverse effects

A

PPE [Hand-foot syndrome] (DLT), myelosuppression (rare), stomatitis, nail discoloration, infusion reaction, fatigue, cardiomyopathy, hyperbilirubinemia, electrolyte disturbance (hyperCa, hypoK, hypoNa), irritant*

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14
Q

How to treat vesicant/irritant injury

A

Discontinue, aspirate extravasated solution, remove needle, APPLY ICE, elevate extremity
EXCEPT apply HEAT for vinca alkaloids, etoposide (cold worsens skin ulceration)

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15
Q

Renal Dose Adjustments

A 
Bleomycin
Carboplatin/Cisplatin
Capecitabine
Cyclophosphamide 
Methotrexate
Mitomycin
Premetrexid
Topotecan
Hydroxyurea
Etoposide
Gemzar
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16
Q

Hepatic Dose Adjustments

A 
Taxol
Adriamycin
Doxil 
Vinka alkaloids 
Irinotecan
5FU
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17
Q

Drugs that Cross the Blood-Brain Barrier

A 
Methotrexate
5FU
Topotecan
Temodar
Niraparib (PARPi)
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18
Q

Fe toxicity

A

Bleomycin
Adriamycin
Doxil

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19
Q

Cardiotoxicity

A 
Adriamycin
Cyclophosphamide
Herceptin (CHF)
5FU
Mitomycin
Taxol (bradycardia)
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20
Q

Palmar-plantar erythrodysesthesia (PPE)

A 
Doxil
5FU
Capecitabine
Taxotere
Sorafenib (tyrosine kinase inhibitor) 
Sunitinib (receptor tyrosine kinase inhibitor)
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21
Q

Pulmonary toxicity

A 
Bleomycin
Gemzar
Methotrexate
Immunotherapies
Melphalin
Mitomycin
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22
Q

Prodrugs

A 
5FU
Mitomycine
Gemzar
Ifosfamide
Cyclophosphamide
Irinotecan
Capecitabine
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23
Q

Secondary malignancy

A 
Melphalan
Cyclophosphamide
Etoposide (>2g lifetime) 
Platinums
Ifosfamide
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24
Q

Vesicants

A 
Vinka alkaloids
Etoposide
Cisplatin
Adriamycin
ActD
Taxol
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25
SIADH
Vinka alkaloids Ifosfamide Cyclophosphamide
26
Bleomycin DLT
Pulmonary toxicity
27
Cisplatin DLT
Nephrotoxicity, ototoxicity
28
Adriamycin DLT
Cardiotoxicity
29
Cyclophosphamide DLT
Myelodysplasia, nephrotoxicity
30
Methotrexate DLT
Stomatitis
31
Ifosfamide DLT
Nephrotoxic, treat with Mesna
32
Platinums DLT
Thrombocytopenia
33
Taxanes DLT
Neurotoxicity / neuropathy
34
Vinka alkaloids DLT
Neurotoxicity
35
Anastrazole DLT
Diarrhea
36
Irinotecan DLT
Diarrhea
37
5FU DLT
Myelodysplasia
38
Avastin DLT
HTN
39
Taxotere DLT
Edema
40
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
41
Carboplatin/Cisplatin MOA
Binds DNA forming crosslinks, denaturation of DNA helix
42
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
43
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 ```
44
Cisplatin adverse effects
Nephrotoxicity (DLT) - do not admin if Cr>1.5ish Ototoxicity** N/V (worse than carbo) Myelosuppression (less than carbo)
45
Paclitaxel (Taxol) dosing
135-175mg/m2 q21d 80-65mg/m2 D1, 8, 15 q21d BSA: cap at 2
46
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
47
Paclitaxel adverse effects
Neurotoxicty/neuropathy (DLT) Myelosuppression (nadir day 10-14, Plt and ANC) Alopecia** Hypersensitivity** - to cremaphor
48
Taxol infusion reaction
Usually with first treatment "Hot seat", chest pain, back pain Flushing, angioedema Hypotension, dyspnea *can re-challenge if not anaphylactic
49
Treating hypersensitivity reaction
1. Stop infusion 2. Evaluate, check VS 3. Give benadryl, steroids, epi if needed 4. Monitor 30-60min 5. If symptoms resolve, can resume at slower rate
50
Neuropathy treatment
B6, gabapentin, amitryptaline, cymbalta
51
Treating chemo nausea
1. Choose anti emetics from multiple classes, treat for D1-3 of cycle Zofran, Aloxi, compazine, emend, ativan (good for anticipatory nausea, anxiolytic) 2. 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
52
Gemcitabine MOA
Pyrimidine analog, antimetabolite. Inhibits DNA synthesis by blocking DNA polymerase and RNA reductase. S phase.
53
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
54
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 ```
55
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 ```
56
Abraxane adverse effects
``` Neutropenia (DLT) Myalgia, arthralgia Alopecia, rash Neuropathy, ocular disturbance N/V/D, electrolyte disturbance (hypoK) ```
57
Abraxane MOA
stabilizes microtubules, mitotic disruption in G2 phase
58
Paclitaxel MOA
mitotic spindle poison, stabilizes microtubules
59
Paclitaxel extravasation antidote
hyaluronidase
60
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
61
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*** ```
62
Adriamycin (doxorubicin) box warning
Cardiomyopathy, extravasation related skin necrosis, secondary malignancy, myelosuppression
63
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). ```
64
Adriamycin adverse effects
``` Cardiotoxicity (DLT - monitor EF) Vesicant - antidote: DMSO, dexrazoxane Fatigue, malaise Mod-high emetogenic (pretreat) Myelosuppression (nadir 10-14d) ```
65
Adriamycin MOA
Inhibits DNA/RNA synthesis, intercalates with Topoisomerase-II causing fragmentation. Also causes free radicals.
66
Minimum approximate EF for administration of Adriamycin?
>/=50%
67
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
68
What are the two forms of doxorubicin, and what cancer are they used for?
Doxil (pegylated liposomal) - ovary | Adriamycin - carcinosarcoma/uterus
69
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
70
What is the reaction to in a taxol chemo reaction?
Cremaphor

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