Colon Cancer Flashcards
What is the median age of colon CA diagnosis?
72
What are risk factors for colon CA?
- age
- AA race
- genetic predisposition (hereditary nonpolyposis colon cancer, familial adenomatosis polyposis)
- other GI conditions
- western diet
- physical inactivity
What are lifestyle modifications to prevent colon CA?
- diet (high fiber, low fat, decreased processed/ grilled red meat, increased antioxidant fruits and vegetables)
- physical activity
- limit alcohol
What is recommended to prevent colon CA if there is a genetic mutation?
NSAIDs
COX-2 inhibitors
What is FDA approved to decrease the number of polyps in patients with familial adenomatosis polyposis?
Celecoxib
What drug is used to prevent colon CA in patients that also require cardiovascular disease prevention?
Aspirin
What is the gold standard for colon CA screening?
colonoscopy
What are options for colon CA screening?
- endoscopy (flexible sigmoidoscopy, colonoscopy)
- stool DNA test
- fecal occult blood test (FOBT)
- Digital rectal exam (DRE)
Which screening method is associated with high false negative rate?
FOBT
How often should someone at average risk get a colonoscopy?
every 10 years
When should screening begin for someone at average risk?
45 years
How often should someone at average risk get a flexible sigmoidoscopy?
5 years
How often should someone at average risk get a stool DNA test?
1-3 years
What are signs and symptoms of colon CA?
- change in bowel habits
- black or red stool
- anorexia
- abdominal pain/ fullness
- weight loss
What are the sites of metastases?
- lymph nodes
- liver
- lung
- brain (rare)
What is required for diagnosis?
- biopsy
- staging scans
Describe stage 1
Local disease;
no invasion into muscular mucosa
Describe stage 2
Invasion into muscular mucosa;
no spread outside of colon
Describe stage 3
lymph node involvement
Describe stage 4
metastatic disease
What is treatment for stage 1?
surgery followed by surveillance
(NO adjuvant chemo/ radiation!)
What is treatment for stage 2?
surgery +/- chemo
When is chemo utilized in stage 2?
poor prognostic factors (large tumor, lymphovascular invasion)
What agents are used for chemo in stage 2?
5-FU + leucovorin
OR
Capecitabine (oral)
What is treatment for stage 3?
surgery + adjuvant chemo for 6 months
What agents are used for chemo in stage 3?
FOLFOX (5-FU + leucovorin + oxaliplatin if tolerated)
OR
CapeOx (capecitabine + oxaliplatin)
What is the MOA of 5-FU?
inhibits thymidylate synthase
Why is leucovorin used with 5-FU?
results in increased cell kill, increases activity by tightening binding between thymidylate synthase and 5-FU
What are the side effects with 5-FU?
myelosuppression
N/V/D
hand-foot syndrome
mucositis
What is the MOA of Capecitabine?
inhibits thymidylate synthase; prodrug of 5-FU
What are side effects with capecitabine?
mucositis
diarrhea
hand-foot syndrome
drug interactions due to oral route
What is the MOA of oxaliplatin?
platinum alkylating agent; cross-linking of DNA causes strands to break
What are side effects with oxaliplatin?
neuropathy of the face, exacerbated by cold
cumulative peripheral neuropathy
myelosuppression
N/V
anaphylaxis/ infusion reactions
What is treatment of stage 4?
palliative chemo
surgery only if bowel obstruction
What agents are used for chemo in stage 4?
FOLFOX
or
CapeOx
or
FOLFURI
+/- monoclonal antibodies
What is FOLFURI?
5-FU
leucovorin
irinotecan
What is the MOA of irinotecan?
inhibits topoisomerase 1; prevents DNA unwinding
What are side effects with irinotecan?
Diarrhea [early (24h) and late (10-14 days after)]
myelosuppression
N/V
hepatotoxicity
What is diarrhea such a severe side effect with irinotecan?
cholinergic response
What is the 1st line regimen for stage 4?
based on expected tolerability; will eventually use all of them
What is the treatment after a complete response is achieved?
6 more months of chemo
What is a partial response? How is it treated?
decrease 30% in size of largest diameter
6 more months of chemo
What is stable disease? How is it treated?
does not meet criteria
6 more months of chemo
What is progressive disease? How is it treated?
20% increase of largest diameter
change regimen and 6 more months of chemo
When can VEGF and EGFR inhibitors be used?
stage 4 only
What is the MOA of VEGF inhibitors?
- inhibition of tumor angiogenesis
- normalization of tumor vasculature
- facilitation of chemotherapy to tumor site
What are the side effects of Bevacizumab (VEGF inhibitor)?
- body wide vasoconstriction–> HTN–> headache
- proteinuria
- wound healing complications
- thromboembolic events
- GI proliferation
When should Bevacizumab be used?
1st/ 2nd line in combination with 5-FU based chemo for metastatic disease
What does increased EGFR expression indicate in colon cancer?
poor prognosis and increased metastatic disease
What predicts a good response to anti-EGFR therapy?
KRAS wild-type
What is the MOA of EGFR inhibitors?
binding of mab to extracellular domain of EGFR inhibits cell growth, promotes apoptosis
decreases production of growth factors
What 2 EGFR inhibitors are used in colon CA?
Cetuximab
Panitumumab
What are side effects of Cetuximab?
- infusion-related reactions
- acneform skinrash
- hypomagnesemia
- diarrhea
What are side effects of Panitumumab?
- infusion-related reactions (less)
- acneform skinrash
- hypomagnesemia
- diarrhea
FOLFOX
5-FU + leucovorin + oxaliplatin
CapeOX
capecitabine + oxaliplatin
