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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
Q

SIADH

A

Vinka alkaloids
Ifosfamide
Cyclophosphamide

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26
Q

Bleomycin DLT

A

Pulmonary toxicity

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27
Q

Cisplatin DLT

A

Nephrotoxicity, ototoxicity

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28
Q

Adriamycin DLT

A

Cardiotoxicity

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29
Q

Cyclophosphamide DLT

A

Myelodysplasia, nephrotoxicity

30
Q

Methotrexate DLT

A

Stomatitis

31
Q

Ifosfamide DLT

A

Nephrotoxic, treat with Mesna

32
Q

Platinums DLT

A

Thrombocytopenia

33
Q

Taxanes DLT

A

Neurotoxicity / neuropathy

34
Q

Vinka alkaloids DLT

A

Neurotoxicity

35
Q

Anastrazole DLT

A

Diarrhea

36
Q

Irinotecan DLT

A

Diarrhea

37
Q

5FU DLT

A

Myelodysplasia

38
Q

Avastin DLT

A

HTN

39
Q

Taxotere DLT

A

Edema

40
Q

Carboplatin dosing

A

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
Q

Carboplatin/Cisplatin MOA

A

Binds DNA forming crosslinks, denaturation of DNA helix

42
Q

Carboplatin adverse effects

A

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
Q

Cisplatin dosing

A 
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
Q

Cisplatin adverse effects

A

Nephrotoxicity (DLT) - do not admin if Cr>1.5ish
Ototoxicity**
N/V (worse than carbo)
Myelosuppression (less than carbo)

45
Q

Paclitaxel (Taxol) dosing

A

135-175mg/m2 q21d
80-65mg/m2 D1, 8, 15 q21d
BSA: cap at 2

46
Q

Paclitaxel infusion instructions?

A

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
Q

Paclitaxel adverse effects

A

Neurotoxicty/neuropathy (DLT)
Myelosuppression (nadir day 10-14, Plt and ANC)
Alopecia**
Hypersensitivity** - to cremaphor

48
Q

Taxol infusion reaction

A

Usually with first treatment
“Hot seat”, chest pain, back pain
Flushing, angioedema
Hypotension, dyspnea

*can re-challenge if not anaphylactic

49
Q

Treating hypersensitivity reaction

A
  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
Q

Neuropathy treatment

A

B6, gabapentin, amitryptaline, cymbalta

51
Q

Treating chemo nausea

A
  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
Q

Gemcitabine MOA

A

Pyrimidine analog, antimetabolite. Inhibits DNA synthesis by blocking DNA polymerase and RNA reductase. S phase.

53
Q

Gemcitabine dosing

A

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
Q

Gemcitabine adverse effects

A 
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
Q

Abraxane (nab-paclitaxel) dosing

A 
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
Q

Abraxane adverse effects

A 
Neutropenia (DLT)
Myalgia, arthralgia
Alopecia, rash
Neuropathy, ocular disturbance 
N/V/D, electrolyte disturbance (hypoK)
57
Q

Abraxane MOA

A

stabilizes microtubules, mitotic disruption in G2 phase

58
Q

Paclitaxel MOA

A

mitotic spindle poison, stabilizes microtubules

59
Q

Paclitaxel extravasation antidote

A

hyaluronidase

60
Q

Docetaxel (Taxotere) dosing

A

60-75mg/m2 q21d
35mg/m2 D1,8,15 q21d
Infuse over 1hr
Premedicate: steroids D0-2 to decrease HS and edema

61
Q

Docetaxel adverse effects

A 
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
Q

Adriamycin (doxorubicin) box warning

A

Cardiomyopathy, extravasation related skin necrosis, secondary malignancy, myelosuppression

63
Q

Adriamycin dosing

A 
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
Q

Adriamycin adverse effects

A 
Cardiotoxicity (DLT - monitor EF)
Vesicant - antidote: DMSO, dexrazoxane
Fatigue, malaise
Mod-high emetogenic (pretreat)
Myelosuppression (nadir 10-14d)
65
Q

Adriamycin MOA

A

Inhibits DNA/RNA synthesis, intercalates with Topoisomerase-II causing fragmentation. Also causes free radicals.

66
Q

Minimum approximate EF for administration of Adriamycin?

A

> /=50%

67
Q

What are the byproducts of ifosfamide and how do you manage the effects?

A

Chloroacetaldehyde - can cause encephalopathy, treat with methylene blue
Acrolein - causes hemorrhagic cystitis; administer ifos with mesna and hydration

68
Q

What are the two forms of doxorubicin, and what cancer are they used for?

A

Doxil (pegylated liposomal) - ovary

Adriamycin - carcinosarcoma/uterus

69
Q

What are the pros/cons of taxotere vs abraxane? Why would you use them instead of taxol?

A

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
Q

What is the reaction to in a taxol chemo reaction?

A

Cremaphor

Fellows 2021! (10 decks)

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