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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
What is the main adjuvant tx for stage 3 colon cancer ?
FOLFOX - fluorouracil focus + oxaliplatin CAPOX = Capecitabine + oxaliplatin Capecitabine - capecitabine focus
26
Which toxicities is common with capecitabine ?
Hand foot syndrome ( red, dry, blister, splitting, pain, tingles) mucositis (painful sores in themouth) Diarrhea ( >4 movements / day)
27
Out of the following , which is a **ORAL** dosing ? capecitabine / Fluorouracil / Oxilaplatin
Capecitabine
28
What are the common SE of the curative TX for CRC ?
N/V ( mild to moderate) myelosuppression ( mild to moderate) Hand-food syndrome Mucositis Diarrhea Peripheral neuropathy
29
Which toxicities is common wit oxaliplatin ?
Peripheral neuropathy and thrombocytopenia Cold dysesthesia ( tingling feeling and stiffness ) , tightening of the jaw and difficulty breathing
30
Oxaliplatin : MOA, Dosage form and drug class
Alkylating agents --> platinum ( blocks the strands formations) IV administered Dosing based on BSA
31
What is the main chemotherapy that showed benefit in stage 3 CRC ?
5- fluorouracil
32
What is the dosage form of capecitabine ?
ORAL tablet
33
What is the MOA of oxaliplatin ?
IV alkylating agent - platinums Creates crosslinks to the DNA BSA dosing
34
What are the counselling tips for someone of oxilaplatin ?
avoid cold drinks washing with cold water m being in cold temp / AC
35
What is the MOA of 5-fluorouracil ?
antimetabolite and is an pyrimidine inhibitor Blocks the thymidylate synthase --> less DNA synthesis and repair IV dosing
36
What are the toxicities of 5 - fluorouracil ?
Stomatitis ( ulcers in the mouth) myelosuppression hand/feet syndrome more common with continuous
37
Which medication increase the efficacy of 5-fluorouracil ? MOA ?
Leucovorin stabilizes the bond with thymidylate synthase
38
What is the MOA of capecitabine ?
ORAL , prodrug to 5-fluorouracil
39
What is a key counselling tip for capecitiabine ?
TAKE it with FOOD (30 mins before food)
40
which of the following drug would require dose changes with renal dysfunction ? leucovorin, fluorouracil, capecitabine
capecitabine
41
What are the common SE of capecitabine ?
Diarrhea ( >4 --> doctor) Mucositis hand-Foot Syndrome
42
What is hand- foot syndrome ?
red and dry palms, soles of the feet blisters, splitting Numbness, tingling and pain
43
What is the usual metastasis of CRC ?
Liver and can be lung
44
What is the addition to tx for stage 4 CRC ?
Biologics ( bevacizumab, cetixumab, panitumumab ) more of a palliative chemo tx FOLFIRI
45
When is oxaliplatin use in the treatment of CRC ?
before is metastases ( stage 3)
46
What are the common biologics for Tx of CRC and when doe sit come in play ?
Bevacizumab Panitumomab Cetuximab Beaver sees poop
47
What is the MOA of irinotecan ?
Topoisomerase 1 inhibitor ( no religation fo the DNA strand)
48
What are the toxicities of irinotecan ?
neutropenia - infection prevention Diarrhea ( COMMON ! due to cholinergic syndrome) ( early vs late onset)
49
Which of the following is known for diarrhea SE ? Fluorouracil, capecitabine, irinotecan, oxilaplatin ?
Irinotecan
50
What can you counsel a patient that will be taking irinotecan ?
Diarrhea --> loperamide or atropine Neutropenia --> prevent infection
51
What can give to a pt on irinotecan caused diarrhea? ( < 24 hours)
atropine to counteract the cholinergic effect
52
What can give to a pt on irinotecan caused diarrhea? ( >24 hours)
Loperamide 4 mg PO asap , 2mg q2h until no diarrhea for 12 hours
53
What is the MOA of an early or late stage diarrhea ?
early = anticholinergic effect late = abnormal ion transport
54
What is the metabolism of irotecan ?
activated to SN38 inactivated to SN38G by UGT141 can be reactivated in the gut by the bacteria
55
How is irinotecan inactivated ?
hepatic UGT1A1 enzymes
56
How is irinitecan activated ?
Activated by CE enzymes of bacterial glucoronidase
57
What is the active drug of irinotecan ?
SN38
58
How long can diarrhea last for late onset diarrhea ?
3 days and start within 5-11 days
59
What is the consequence of UGT1A1 deficiency ?
irinotecan is not metabolised into the inactive form --> more toxicities diarrhoea, especially neutropenia
60
What is the main difference between predictive and prognostic biomarker?
predictive is to monitor the efficacy of the tx prognostic is the indicative of the pt survival and the progression of the tumour
61
What is the better combinition with bevacizumab for stage 4 CRC ?
FOLFIRI
62
What is the MOA of bevacizumab ?
recombinant humanized monoclonal ab that BLOCKS VEGF receptors - inhibits angiogenesis
63
What are main side effects of bevacizumab ?
HTN / thromboebolism impaired wound healing hemorrahge proteinuria
64
What is the MOA of cetuximab and panitumumab ?
epithelial growth factor receptor EGFR --> HER1 inhibitors inhibits the cell growth and induction of apoptosis by blocking the PO4-
65
Which of the HER1 inhibitors induces internalization and degradation of those receptors?
cetuximab
66
What is a possible resistance to cetixumab / pantitumumab ?
mutations to downwards parts gene : KRAS, NRAS or even BRAF they are not Wild TYPE ! those therapies will not work
67
What are the SE of EGFR target Mabs
Infusion rxn ( chills, fever and dyspnea) rash ( acneiform) Diarrhea Hair/nails changes
68
Which side of CRC growth has better outcomes with MAb ?
Left side ( distal to the primary tumours) also add chemo + biologics ( EGFRi)
69
What is good additional TX for Met-CRC on right side ?
Bevacizumab ( VEGF --> stops angiogenesis)
70
Which CRC tx should not be used together ?
EGFR MAbs ( pani or cetu) and bevacizumab
71
What is the age that has more potential of Colon Cancer ?
Age > 55

PHARM 444 : Neurology/Oncology (10 decks)

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