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PHARM 444 : Neurology/Oncology > Lecture 2 > Flashcards

Lecture 2 Flashcards

Colon Cancer

1
Q

What are the diseases that can increase the risk of colon cancer ?

A

Inherited disorders like FAP or Lynch Syndrome, IBD ( crohns or UC)

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2
Q

At what age can pts receive CRC diagnosis ?

A

> 55 years old

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3
Q

What are modifiable factors that can increase risk of colon cancer ?

A

Diabetes
Obesity
lifestyle ( smoking, alcohol, low physical activities, diet )

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4
Q

What is the screening process for colon cancer ?

A

average not symptomatic age 50-74
FIT q1 year –> if positive –> colonoscopy —> normal redo every 10 years

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5
Q

Who is not qualified for a FIT test ?

A

symptomatic patient for colon cancer

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6
Q

at what age is FIT much more debatable ?

A

> 75 years old
patient might bleed in the colonoscopy if the FIT test is positive
general practice - asymptomatic with life expectancy of < 10 years , don’t screen

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7
Q

When would a FIT test be recommended ? ( increased risk)

A

1st degree family relative @ 60 yo
get FIT at 40 years old every 1-2 years

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8
Q

When would a colonoscopy be recommended ?

A

persona history of Colon cancer, IBD, adenomas , lynch syndrome, FAP
1st degree relative < 60 yo with colon cancer ( or high risk) or two more affected relatives

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9
Q

What is FIT test ?

A

using ab for human blood to detect in the stool
Reduce CRC by 25-45 %

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10
Q

What is tenesmus, and how is it related to colorectal cancer?

A

Tenesmus is the feeling of needing to evacuate the bowels even when the bowels are empty. It can be a symptom of colorectal cancer, indicating irritation or obstruction in the rectum or lower intestines.

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11
Q

What is Ileus ?

A

Obstruction of the ileum or other part of the bowel

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12
Q

What are the signs and symptoms of colon cancer ?

A

Change in bowel habits
* Tenesmus: Recurrent inclination to evacuate the bowels

  • Change in stool shape
  • Melena: Dark sticky feces (containing partly digested blood)
  • Weight loss (unexplained)
  • Fatigue
  • Pallor (pale)
  • Ileus: Obstruction of ileum or other part of the bowel
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13
Q

What needs to be considered before the surgery for colon cancer ?

A

Colonoscopy to rule out other masses
CT scan looking for other metastates
Pre-operative CEA ( post if the pre was elevated )

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14
Q

What is the purpose of CEA ?

A

prognostic biomarker of poor survival

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15
Q

What is the 5 yo OS by each stage of colon cancer ?

A

Stage 1 - 93%
stage2 - 78%
Stage 3 - 64%
Stage 4 - 8%

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16
Q

For CRC , what is the most important prognostic factor ?

A

Stage

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17
Q

what is the goals of therapy for CRC stage 1-3 ?

A

CURE
minimize the SE
maintain and improve QofL

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18
Q

What is the goals of therapy for CRC stage IV ?

A

Curable ? –> may be resectable if spreads to the liver, lungs

most are NOT CURABLE = minimize SE and maintain QofL

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19
Q

What does negative margins means ?

A

all the cancer was removed from the site

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20
Q

What is the typical treatment course of action for stage1,2,3 of colon cancer ?

A

surgical resection if possible
following by a stoma to allow the site to heal

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21
Q

When would you recommend a permanent colostomy ?

A

if the tumour is lower in the rectum

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22
Q

What tx or services can be provided at stage 0/1 ?

A

Observation
Colonoscopy at 1, 3, 5 years
adjuvant therapy is not indicated

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23
Q

In what setting would stage 2 colon cancer receive adjuvant tx ?

A

high risk features from the tumours
high grade tumour ( not greatly differentiated cells)
perforation/obstruction
invasion of the lymphatic
positive surgical margins

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24
Q

Why is Fluorouracil preferred as antineoplastic agent for stage 3 CRC?

A

reduced relative risk by ~ 30%

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25
Q

What is the main adjuvant tx for stage 3 colon cancer ?

A

FOLFOX - fluorouracil focus + oxaliplatin
CAPOX = Capecitabine + oxaliplatin
Capecitabine - capecitabine focus

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26
Q

Which toxicities is common with capecitabine ?

A

Hand foot syndrome ( red, dry, blister, splitting, pain, tingles)
mucositis (painful sores in themouth)
Diarrhea ( >4 movements / day)

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27
Q

Out of the following , which is a ORAL dosing ?

capecitabine / Fluorouracil / Oxilaplatin

A

Capecitabine

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28
Q

What are the common SE of the curative TX for CRC ?

A

N/V ( mild to moderate)
myelosuppression ( mild to moderate)
Hand-food syndrome
Mucositis
Diarrhea
Peripheral neuropathy

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29
Q

Which toxicities is common wit oxaliplatin ?

A

Peripheral neuropathy and thrombocytopenia
Cold dysesthesia ( tingling feeling and stiffness ) , tightening of the jaw and difficulty breathing

30
Q

Oxaliplatin : MOA, Dosage form and drug class

A

Alkylating agents –> platinum ( blocks the strands formations)
IV administered
Dosing based on BSA

31
Q

What is the main chemotherapy that showed benefit in stage 3 CRC ?

A

5- fluorouracil

32
Q

What is the dosage form of capecitabine ?

A

ORAL tablet

33
Q

What is the MOA of oxaliplatin ?

A

IV alkylating agent - platinums
Creates crosslinks to the DNA
BSA dosing

34
Q

What are the counselling tips for someone of oxilaplatin ?

A

avoid cold drinks
washing with cold water m
being in cold temp / AC

35
Q

What is the MOA of 5-fluorouracil ?

A

antimetabolite and is an pyrimidine inhibitor
Blocks the thymidylate synthase –> less DNA synthesis and repair
IV dosing

36
Q

What are the toxicities of 5 - fluorouracil ?

A

Stomatitis ( ulcers in the mouth)
myelosuppression
hand/feet syndrome more common with continuous

37
Q

Which medication increase the efficacy of 5-fluorouracil ?
MOA ?

A

Leucovorin
stabilizes the bond with thymidylate synthase

38
Q

What is the MOA of capecitabine ?

A

ORAL , prodrug to 5-fluorouracil

39
Q

What is a key counselling tip for capecitiabine ?

A

TAKE it with FOOD (30 mins before food)

40
Q

which of the following drug would require dose changes with renal dysfunction ?

leucovorin, fluorouracil, capecitabine

A

capecitabine

41
Q

What are the common SE of capecitabine ?

A

Diarrhea ( >4 –> doctor)
Mucositis
hand-Foot Syndrome

42
Q

What is hand- foot syndrome ?

A

red and dry palms, soles of the feet
blisters, splitting
Numbness, tingling and pain

43
Q

What is the usual metastasis of CRC ?

A

Liver and can be lung

44
Q

What is the addition to tx for stage 4 CRC ?

A

Biologics ( bevacizumab, cetixumab, panitumumab )
more of a palliative chemo tx

FOLFIRI

45
Q

When is oxaliplatin use in the treatment of CRC ?

A

before is metastases ( stage 3)

46
Q

What are the common biologics for Tx of CRC and when doe sit come in play ?

A

Bevacizumab
Panitumomab
Cetuximab

Beaver sees poop

47
Q

What is the MOA of irinotecan ?

A

Topoisomerase 1 inhibitor ( no religation fo the DNA strand)

48
Q

What are the toxicities of irinotecan ?

A

neutropenia - infection prevention
Diarrhea ( COMMON ! due to cholinergic syndrome) ( early vs late onset)

49
Q

Which of the following is known for diarrhea SE ?

Fluorouracil, capecitabine, irinotecan, oxilaplatin ?

A

Irinotecan

50
Q

What can you counsel a patient that will be taking irinotecan ?

A

Diarrhea –> loperamide or atropine
Neutropenia –> prevent infection

51
Q

What can give to a pt on irinotecan caused diarrhea? ( < 24 hours)

A

atropine to counteract the cholinergic effect

52
Q

What can give to a pt on irinotecan caused diarrhea? ( >24 hours)

A

Loperamide 4 mg PO asap , 2mg q2h until no diarrhea for 12 hours

53
Q

What is the MOA of an early or late stage diarrhea ?

A

early = anticholinergic effect
late = abnormal ion transport

54
Q

What is the metabolism of irotecan ?

A

activated to SN38
inactivated to SN38G by UGT141
can be reactivated in the gut by the bacteria

55
Q

How is irinotecan inactivated ?

A

hepatic UGT1A1 enzymes

56
Q

How is irinitecan activated ?

A

Activated by CE enzymes of bacterial glucoronidase

57
Q

What is the active drug of irinotecan ?

58
Q

How long can diarrhea last for late onset diarrhea ?

A

3 days and start within 5-11 days

59
Q

What is the consequence of UGT1A1 deficiency ?

A

irinotecan is not metabolised into the inactive form –> more toxicities

diarrhoea, especially neutropenia

60
Q

What is the main difference between predictive and prognostic biomarker?

A

predictive is to monitor the efficacy of the tx
prognostic is the indicative of the pt survival and the progression of the tumour

61
Q

What is the better combinition with bevacizumab for stage 4 CRC ?

62
Q

What is the MOA of bevacizumab ?

A

recombinant humanized monoclonal ab that BLOCKS VEGF receptors - inhibits angiogenesis

63
Q

What are main side effects of bevacizumab ?

A

HTN / thromboebolism
impaired wound healing
hemorrahge
proteinuria

64
Q

What is the MOA of cetuximab and panitumumab ?

A

epithelial growth factor receptor EGFR –> HER1 inhibitors

inhibits the cell growth and induction of apoptosis by blocking the PO4-

65
Q

Which of the HER1 inhibitors induces internalization and degradation of those receptors?

66
Q

What is a possible resistance to cetixumab / pantitumumab ?

A

mutations to downwards parts gene : KRAS, NRAS or even BRAF

they are not Wild TYPE !
those therapies will not work

67
Q

What are the SE of EGFR target Mabs

A

Infusion rxn ( chills, fever and dyspnea)
rash ( acneiform)
Diarrhea
Hair/nails changes

68
Q

Which side of CRC growth has better outcomes with MAb ?

A

Left side ( distal to the primary tumours)
also add chemo + biologics ( EGFRi)

69
Q

What is good additional TX for Met-CRC on right side ?

A

Bevacizumab ( VEGF –> stops angiogenesis)

70
Q

Which CRC tx should not be used together ?

A

EGFR MAbs ( pani or cetu) and bevacizumab

71
Q

What is the age that has more potential of Colon Cancer ?

PHARM 444 : Neurology/Oncology (10 decks)

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