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62 Cards in this Set

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Where is the incidence of CC most common?
Industrialized nations such as North America, Western Europe, Australia and New Zealand
Colorectal cancer is the ____ leading incidence of cancer and cancer death in the USA.
3rd
Why has there been a decrease in the incidence of colorectal cancer in the past decade?
The decrease of white females
What are general risk factors for Colorectal Cancer?
Age >40, Family history, Diet (Fat, low fiber), obesity, alcohol/tobacco use (nicotine reduces risk)
Heriditary nonpolyposis colon cancer (HNPCC) is also known as ____________.
Lynch syndrome
Describe Lynch Syndrome
Autosomal Dominant, Accounts for 5-10%, early onset <40yo, occurs predominantly in proximal colon with less than 100 polyps.
Describe FAP/Familial adenomatous polyposis
Autosomal dominant trait, 0.5% of cases, Mutation of adenomatous polyposis coli (APC) gene on chromosone 9.
100% of developing malignancy, screening starts at age 12 and surgical colectomy occurs when polyps are detected.
What pre-existing conditions can act as risk factors for Colorectal Cancer?
IBD: Chronic UC, Crohn's disease
Describe 6 Primary Prevention strategies for Colorectal Cancer
1. Dietary Fiber
2. Reduction of dietary fat
3. Calcium rich diet
4. Diet high in antioxidant fruits/vegetables (folic acid)
5. ASA/NSAIDs
6. COX-2 Inhibitors, Celecoxib 400mg BID in FAP reduces polyp number significantly
How do COX-2 inhibitors help prevent colorectal cancer?
COX inhibition decreases COX-2 mediated free radical formation and probably inhibits growth factor synthesis in response to tumor promotors.
Describe Secondary Prevention for Colorectal Cancer
Polypectomy via conoloscopy or total colectomy for FAP or high risk patients.
Describe some techniques for screening/dx of colorectal cancer
1. Fecal occult blood test
2. Digital Rectal Screening
3. Sigmoidoscopy (rigid vs flexible)
4. Colonoscopy
5. Barium Enema
6. Serum markers (CEA, CA19-9)
What are some important points about the Fecal occult blood test?
Has a high false negative rate, decreases mortality by one third and increased sensitivity/specificity when used in combination with other methods.
Describe screening guidelines for average risk patients
1.Annual DRE + FOBT after age 50 years.
2.Sigmoidoscopy q 5 years
3.Colonoscopy q 10 years
4.Barium enema q 5-10years
When does screening begin for patients with a family history of colorectal cancer?
35-40 years
When does screening begin for patients with HNPCC?
30 yo
When does screening begin for patients with FAP?
12 yo
What Signs/Sx would exist for early stage colorectal disease?
Asx, Abdominal pain, Changes in bowel habits, flatulence, blood in stool, anemia
Describe Signs/Sx of Left sided colon (descending) Late stage disease
Constipation, abdominal pain, obstructive Sx (NV)
Describe Sign/Sx of Right sided colon (ascending) late stage disease?
Vague abdominal aching, anemia (Elderly, Fe deficiency), Weakness, Weight loss
Use for surgery for Colorectal cancer
Treatment of choice for primary tumor removal and for debulking in metastatic disease
Describe surgery for colorectal cancer
Complete resection of tumor and regional lymphadenectomy. <1/3 require permanent colostomy but temporary may be used.
What are some complications of colorectal cancer surgery?
Infection, bowel obstruction, anastmotic leakage, incontinence, impotence, locoregional recurrence.
For what type of colorectal cancer is radiation predominantly used?
Rectal, not colon
What are the acute effects of radiation?
Bone marrow suppression, dysuria, diarrhea, abdominal cramping and proctitis
What are the acute effects of rectal irradiation?
Bone marrow suppression, dysuria, diarrhea, abdominal cramping and proctitis
What are the chronic effects of rectal irradiation?
Persistent diarrhea, proctitis, enteritis, small bowel obstruction, perineal tenderness and impaired wound healing
What enzyme affects metabolism and toxicity of 5-FU?
Dihydropyrimidine dehydrogenase. Deficiency will result in severe toxicity
Describe the impact a person with Dihydropyrimidine dehydrogenase will have on their chemo therapy for cholorectal cancer?
It will result in severe 5-FU toxicity since this enzyme is responsible for its metabolism.
IV Bolus/Push 5-FU is associated with __________.
Neutropenia (Jen, this doesn't contradict Stockwell's notes)
IV Infusion of 5-FU is associated with _______________.
Hand-foot syndrome and stomatitis.
What is another name for hand-foot syndrome?
Palmar-plantar erythrodysthesia
Why is leucovorin used with 5-FU?
to stabilize the fdUMP and TS complex resulting in greater cytotoxicity of 5-FU
What are the 1st line agent for Colorectal cancer chemo-wise?
5-FU and leucovorin + Irinotecan
Describe the overall dosing pattern of 5-FU/Leucovorin in terms of Colorectal cancer
5-FU bolus x 5 days every four weeks with low or high dose leucovorin
Describe the Mayo Clinic regimen for 5-FU/Leucovorin for colorectal cancer.
5-FU 425mg/m2 IVP + Leucovorin 20mg/m2 IVP weekly
Describe the Roswell Park regimen for 5-FU/Leucovorin for colorectal cancer.
Leucovorin 500mg/m2 over 2 hours + 5-FU 500mg/m2 IVP given at midpoint of infusion weekly.
Describe how Capecitabine/Xeloda is similar to 5-FU
It is an oral prodrug that requires three enzymatic steps for activation.
Describe Capecitabine dosing
1250mg/m2 BID for 14 days then 1 week rest for 8 cycles.
Predominant toxicity associated with Capecitabine/Xeloda
Hand-foot syndrome/Stomatitis
IFL
Irinotecan, 5-FU, Leucovorin (Bolus)
1st line regimen
FOLFIRI
Irino, infusion of 5-fu/Leucovorin
1st line regimen
FOLFOX
Oxaliplat, infusion FU/LEUC
1st/2nd line regimen
IV FU/Bevacizumab, regimen line?
Also a 1 st line regimen
Indication for Irinotecan/Cetuximab
Refractory disease
How (regimen-wise) is Oxaliplatin used for colorectal cancer?
It is used incombinations such as FOLFOX and sequentially in metastatic disease
What is the dose limiting side effect of Oxaliplatin
Peripheral neuropathy. Temperature sensitive dysethesia occurs, usually with cold
Describe what test must be done before administering Irinotecan and its ramifications.
Must detect UGT1A1 deficiency. To do this give rifampin 900mg, measure bilirubin 4 hours later, if >1.8--> deficiency.
Those with UGT1A1 deficiency will experience what toxicities from Irinotecan
Diarrhea, mucositis, hemat. tox
Can you still use Irinotecan in patients with UGT1A1 deficiency?
Yes, simply reduce the dose by 20%
What are the dose limiting side effects associated with Irinotecan?
Diarrhea/Stomatitis. Remember the acute/delayed Tx for Diarrhea... early would be atropine later will be loperamide.
Irinotecan is typically used in the ___________ regimen or the ___________ regimen.
FOLFIRI --> FU/Leuc Infusion + Irinotecan
IFL can use as well, Bolus FU/Leuc + Irinotecan
Two major treatment categories for METASTATIC colorectal cancer
Surgery + Chemotherapy
What organ is typically affected by metastatic colorectal disease. Hint: Not the colon or rectum...
Liver, thus resection of isolated hepatic metastases can improve survival but no cure.
2 Major Chemotherapy agents used for Metastatic colorectal cancer.
Bevacizumab/Avastin or Cetxuimab
Describe MOA of Bevacizumab
MAB directed at VEGF. Can be combined with FOLFOX or FOLFIRI
Regimens containing which agent are bumped to second line?
Oxaliplatin
ADR associated with Bevacizumab
Gastric perforation, hemorrhage, arterial thromboembolic disease, HTN, asthenia, pain and proteinuria.
What regimens can bevacizumab be used with?
FOLFIRI or FOLFOX
Of all those wonderful regimen abbreviations, which one is the only BOLUS one...?
IFL, the shorter name!
Cetuximab MOA
MAB directed at EGFR.
According to Shane Scott, what do you need to premedicate cetuximab patients with?
Diphenhydramine