Exam 2 lecture 5 (colorectal)

Question 1

How is colon cancer ranked in terms of incidence and death in men and women? Where is incidence high?

Answer 1

3rd in incidence an death for both. Incidence high in industrialized nations

Question 2

risk factors for colon cancer

Answer 2

Age- increases strating age 40. is greater after 50.
FH
dietary factors (high fat, low fiber
polyps

Question 3

What is a hereditary syndrome that puts people at risk of colon cancer? WHen does screening start for this condition?

Answer 3

1. Familial adenomatous polyposis (FAP)
   (development of 1000s of adenomatous polyps. 100% life time risk for colon cancer.
   screening starts at 10-12 yrs old
2. Hereditary nonpolyposis colorectal cancer (HNPCC)
   early age of onset (40-45)
   80& risk of cancer development

Question 4

What are warning signs of colon cancer?

Answer 4

Constipation
diarrhea
blood in stools
narrow stools
unexplained anemia
abdominal pain
weight loss
weakness/fatigue

Question 5

how is colorectal cancer presented

Answer 5

May be asymptomatic
Presents with rectal bleeding with anemia.
N/v
20-25% will present with metastatic disease

Question 6

all patients with colon cancer should be tested for what

Answer 6

defective mismatch repair (dMMR) and microsatalite- high level instability (MSI-H)

Question 7

What do dMMR or MSI-H tumors predict?

Answer 7

Predict decreased benefit from adjuvant 5-FU based therapy for STAGE II disease

stage III patients with dMMR or MSI-H disease CAN BENEFIT from adjuvant 5-FU

Question 8

What are the treatment options for colorectal cancer

Answer 8

surgery
radiation therapy
chemo

Question 9

how to treat stage I and II colon cancer

Answer 9

surgery alone is definitive therapy for stage I and stage II with MSI-h and/or MMR.

for stage II without MSI and/or MMR we do surgery and chemo

Question 10

WHat chemo options for stage II colon cancer without MMR and MSI-h? What do they stand for?

Answer 10

FOLFOX and capeOX

FOLFOX- 5-FU, leucovorin and oxaliplatin (for high/intermediate risk stage II pts)
capeOX- capecitabine, oxaliplatin

Question 11

How to treat stage III colon cancer

Answer 11

surgery (regional lymph node removal)
chemotherapy is indicated for this stage

Question 12

what are the chemo options for stage III colon cancer

Answer 12

FOLFOX
capeOX

Question 13

What is the regimen for stage III colon cancer depending on the risk

Answer 13

low risk- capeOX 3 months or FOLFOX 3-6 months

High risk- capeox for 3-6 months
FOLFOX for 6 months

Question 14

What are some regimen considerations when choosing between FOLFOX and capeOX for colon cancer

Answer 14

FOLFOX- requires port, 2-day pump, more infusions overall, increased myelosuppression and mouth sores

capeOX- port not required, less infusion overall, increased hand foot syndrome, capecitabine has renal dose adjustment

Question 15

How is advanced/metastatic colon cancer treated? WHat do we take into consideration

Answer 15

Chermotherapy is mainstay in colon cancer.
FOLFOX, capeOX, FOLFIRI, FOLFIRINOX (+ bevacizumab)

UGT1A1 deficiency and neuropathy are things we take into consideration

Question 16

for advanced colon cancer with either UGT1A1 and neuropathy

Answer 16

UGT1a1 deficiency- we do NOT use irinotecan
neuropathy- we would NOT use oxaloplatin

Question 17

How do we treat advanced colon cancer with MMR or MSI-H

Answer 17

FOLFOX/FOLFIRI

with

pembrolizumab and nivolumab

Question 18

What drugs do we give with KRAS wild type (WT) and never with KRAS mutation with advanced metastatic colon cancer

Answer 18

cetuximab or panitumumab

Question 19

What are some accepted chemo regimens if someone can not tolerate intensive chemo

Answer 19

no targetable mutations- 5-FU + leucovorin (capecitabine +/- bevacizumab)

KRAS WT, left sided- cetuximab/panitumumab

dMMR/MSI-H nivolumab +/- ipilimumab with pembrolizumab

HER2 positive- trastuzumab + (pertuzumab or lapatinib or tucatinib)

Question 20

2nd line therapy for advanced colon cancer

Answer 20

Basically just switch therapy (i.e if they already received oxaliplatin based regimen, give irinotecan regimen like FOLFIRI

if patient was started on irinotecan regimen, give oxaliplatin based regimens (FOLFOX)

Question 21

What are side effects with 5-FU? What enhances its effects?

Answer 21

diarrhea. mucositis, myelosuppression

leucovorin enhances its effects

Question 22

side effects of oxaliplatin

Answer 22

cold intolerance, neuropathy

Question 23

Bevacizumab side effects

Answer 23

bleeding and high blood pressure (elevated BP may cause holding of drug that day), proteinuria

Question 24

what are colon cancer screening tests

Answer 24

1. primarily detect cancer
   - fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT)

or

2. Detect cancer and advanced lesions
   - endoscopic and radiologic exams

Question 25

cons about FOBT? How to avoid them?

Answer 25

has high false negative rate

to avoid false negatives- avoid red meat and raw vegetables 3 days prior to testing

avoid vitamin C supplements and citrusy juices and fruits 3 days prior to testing

AVoid aspirin/NSAIDs, enemas

avoid testing until after 3 days after menstrual bleeding ended and avoud testing if hemmorhoids present

Question 26

What type of tests are FIT and FOBT? Compare them

Answer 26

Test to primarily detect colon cancer ( not advance dlesions)

FIT has no false negative rate

Question 27

What are tests to primarily detect cancer and advanced lesions

Answer 27

Endoscopy and colonoscopy

Question 28

screening guidelines for colon cancer for average risk, FH, HNPCC and FAP?

Answer 28

Average risk- start 45 yo, annual FOBT or FIT or colonoscopy every 10 years

FH- annual screening at age 40

HNPCC- annual screening age 20-25

FAP- annual screening age 10-12

Question 29

Colon cancer prevention

Answer 29

High fiber, low fat diet

calcium rich diet

aspirin/NSAID

colectomy

Question 30

MOA of 5-FU? What is it metabolized by in body? Common toxicities?

Answer 30

moa- 5-FU is converted invitro to FTUP and FDUMP.
FDUMP binds thymidylate synthase (TS) and reduces rate of DNA synthesis, replication and repair.

it is extensively metabolized by DPD in liver. Pts with DPD deficiency have exaggerated toxicities.

toxicities- diarrhea, mucositis, myelosuppression

Question 31

What is the prodrug of irinotecan? What are the dose limiting toxicities? What is a side effect that is very prevalent with this drug? WHat causes increased toxicity with irinotecan

Answer 31

Prodrug- SN-38
Dose limiting toxicities are diarrhea and neutropenia

Early onset diarrhea and late onset diarrhea are big side effects of the drug (early can happen while patient is receiving drug)

late inset starts more than 24 hrs after irinotecan administration. Start anti diarrheal treatment for both these

UGT1a1 deficiency causes increased toxicity

Question 32

what is capecitabine? Dose limiting toxicity?

Answer 32

dose limiting side effects- Hand foot syndrome and diarrhea
Oral prodrug of 5-FU

Question 33

Unique toxicity of oxaliplatin

Answer 33

COld intolerance, neuropathy and sensation of not being able to breathe

Question 34

WHat is cetuxaimab used in? Adverse effects?

Answer 34

Only used in KRAS wildtype patients

advrese events include acne form rash and hypomagnesemia

Question 35

what does panitumumab bind to? toxicity?

Answer 35

binds to EGFR
dane toxicity as cetuximab (acneform rash and hypomagnesemia)