Exam 2 lecture 5 (colorectal) Flashcards
How is colon cancer ranked in terms of incidence and death in men and women? Where is incidence high?
3rd in incidence an death for both. Incidence high in industrialized nations
risk factors for colon cancer
Age- increases strating age 40. is greater after 50.
FH
dietary factors (high fat, low fiber
polyps
What is a hereditary syndrome that puts people at risk of colon cancer? WHen does screening start for this condition?
- Familial adenomatous polyposis (FAP)
(development of 1000s of adenomatous polyps. 100% life time risk for colon cancer.
screening starts at 10-12 yrs old - Hereditary nonpolyposis colorectal cancer (HNPCC)
early age of onset (40-45)
80& risk of cancer development
What are warning signs of colon cancer?
Constipation
diarrhea
blood in stools
narrow stools
unexplained anemia
abdominal pain
weight loss
weakness/fatigue
how is colorectal cancer presented
May be asymptomatic
Presents with rectal bleeding with anemia.
N/v
20-25% will present with metastatic disease
all patients with colon cancer should be tested for what
defective mismatch repair (dMMR) and microsatalite- high level instability (MSI-H)
What do dMMR or MSI-H tumors predict?
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
What are the treatment options for colorectal cancer
surgery
radiation therapy
chemo
how to treat stage I and II colon cancer
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
WHat chemo options for stage II colon cancer without MMR and MSI-h? What do they stand for?
FOLFOX and capeOX
FOLFOX- 5-FU, leucovorin and oxaliplatin (for high/intermediate risk stage II pts)
capeOX- capecitabine, oxaliplatin
How to treat stage III colon cancer
surgery (regional lymph node removal)
chemotherapy is indicated for this stage
what are the chemo options for stage III colon cancer
FOLFOX
capeOX
What is the regimen for stage III colon cancer depending on the risk
low risk- capeOX 3 months or FOLFOX 3-6 months
High risk- capeox for 3-6 months
FOLFOX for 6 months
What are some regimen considerations when choosing between FOLFOX and capeOX for colon cancer
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
How is advanced/metastatic colon cancer treated? WHat do we take into consideration
Chermotherapy is mainstay in colon cancer.
FOLFOX, capeOX, FOLFIRI, FOLFIRINOX (+ bevacizumab)
UGT1A1 deficiency and neuropathy are things we take into consideration
for advanced colon cancer with either UGT1A1 and neuropathy
UGT1a1 deficiency- we do NOT use irinotecan
neuropathy- we would NOT use oxaloplatin
How do we treat advanced colon cancer with MMR or MSI-H
FOLFOX/FOLFIRI
with
pembrolizumab and nivolumab
What drugs do we give with KRAS wild type (WT) and never with KRAS mutation with advanced metastatic colon cancer
cetuximab or panitumumab
What are some accepted chemo regimens if someone can not tolerate intensive chemo
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)
2nd line therapy for advanced colon cancer
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)
What are side effects with 5-FU? What enhances its effects?
diarrhea. mucositis, myelosuppression
leucovorin enhances its effects
side effects of oxaliplatin
cold intolerance, neuropathy
Bevacizumab side effects
bleeding and high blood pressure (elevated BP may cause holding of drug that day), proteinuria
what are colon cancer screening tests
- primarily detect cancer
- fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT)
or
- Detect cancer and advanced lesions
- endoscopic and radiologic exams
cons about FOBT? How to avoid them?
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
What type of tests are FIT and FOBT? Compare them
Test to primarily detect colon cancer ( not advance dlesions)
FIT has no false negative rate
What are tests to primarily detect cancer and advanced lesions
Endoscopy and colonoscopy
screening guidelines for colon cancer for average risk, FH, HNPCC and FAP?
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
Colon cancer prevention
High fiber, low fat diet
calcium rich diet
aspirin/NSAID
colectomy
MOA of 5-FU? What is it metabolized by in body? Common toxicities?
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
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
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
what is capecitabine? Dose limiting toxicity?
dose limiting side effects- Hand foot syndrome and diarrhea
Oral prodrug of 5-FU
Unique toxicity of oxaliplatin
COld intolerance, neuropathy and sensation of not being able to breathe
WHat is cetuxaimab used in? Adverse effects?
Only used in KRAS wildtype patients
advrese events include acne form rash and hypomagnesemia
what does panitumumab bind to? toxicity?
binds to EGFR
dane toxicity as cetuximab (acneform rash and hypomagnesemia)
