21 - Colorectal Cancer Flashcards
__% curable if detected early
90
Without effective screening, it will remain the most common cause of cancer death in ___-_____
non-smokers
Describe the colon
- Large intestine
- From ileum to rectum
- Functions to absorb water and electrolytes
Describe the rectum
- From sigmoid colon to anus
- Functions to store stool
Describe the risk of age for colorectal cancer
-begins at age 40, and increases with age, with the mean age at presentation being 70 years
Risks for colorectal cancer
- Age
- Family history
- Alcohol intake
- Diet (high in red meats and processed meats, low in fresh fruits and vegetables)
- Smoking
- Obesity
- Inflammatory bowel disease
More than 95% of primary colorectal cancers are _________
adenocarcinomas
*this is good bc these types are sensitive to chemo and radiation
When doing surgery, what do we want to remove?
- want at least 1 cm of healthy tissue around tumor removed
- need lymph nodes to be removed so pathologist can evaluate them
- at least 14 lymph nodes
What are some signs and symptoms of colorectal cancer?
- Change in bowel habits
- Tenesmus
- Diarrhea or constipation
- Blood in the stool
- Narrow stools
- Abdominal discomfort and gas pains
- Weight loss
What is FOBT
fecal occult blood test
What sorts of treatment do we have for colorectal cancer?
1) Surgery
- The primary curative procedure for patients with stages 1, 2, and 3 disease is surgical resection of the bowel (ex. hemicolectomy or abdominoperineal section
- Resection of isolated liver and/or lung metastases
2) Radiation:
- Rectal carcinomas are associated with a local recurrence rate much higher than colon cancers. Approximately 25% of stage 2 rectal cancers and 50% of stage 3 rectal cancers may recur after surgery with no further therapy. Adjuvant radiation to the tumor bed, as well as the surgically inaccessible areas of tissue has been shown to decrease local recurrence
- Additionally, radiation can be used for palliation of symptoms
Is radiation done in colon cancer or rectal cancer ?
Only done in rectal surgery
Colon:
- surgery
- chemo
Rectum:
- surgery
- chemo
- radiation
What are metastatic sites common in colorectal cancer?
- liver
- lung
- bone
When is chemotherapy used?
In the adjuvant setting after surgical resection of Stage 2 and Stage 3 cancers.
Despite the high rate of respectability, almost half of all patients with colorectal cancer will recur because of residual disease not apparent at the time of surgery. This is the primary reason for adjuvant therapy
Describe Fluorouracil (FU)
- Most used agent in colorectal cancer
- Similar to the pyrimidine, uracil (RNA base)
- Used in both the adjuvant and metastatic setting.
- Until recently, the drug of first choice in the adjuvant setting, in combination with leucovorin
- Pattern of FU toxicity differs between bolus administration and continuous infusion
Fluorouracil (FU):
Grade 3 and 4 ______ toxicity is more common with bolus regimens
hematological
*bolus injection will also cause a lot more neutropenia and diarrhea
Fluorouracil (FU)
infusion regimens are more likely to show ______ syndrome
hand-foot
Fluorouracil (FU)
Essential component of which regimens ?
of selected irinotecan or oxaliplatin regimens
What is hand-foot syndrome?
How do you prevent and treat it?
- Painful reddening of the skin that can proceed to desquamation
- Patients should be counselled to report any changes to palms and soles ASAP when taking FU
- Prevention measures include moisturizing liberally and avoiding sources of heat and friction
- Treatment measures include topical anaesthetics, application of cold, & oral analgesics
Describe Irinotecan
- Analogue of camptothecin
- Top 1 inhibitor
- Used in the metastatic setting
- Activity in patients with FU-resistant disease as a single agent
- Currently the first line agent for Tx of metastatic colorectal cancer in combination with FU and leucovorin
- More favorable toxicity profile with regimens that contain protracted infusion regimens of FU versus bolus FU
SE of Irinotecan
diarrhea!
early onset and late onset
*can give with loperamide
Irinotecan:
used for adjuvant or metastatic
- metastatic
- results have been disappointing in the adjuvant setting
What is the 1st line Tx for colorectal cancer?
- Irinotecan
- FU
- Leucovorin
What is the max dose of Loperamide a person can take if on Irinotecan?
32 mg/day
Describe Oxaliplatin
- third generation platinum analog
- approved for both adjuvant and metastatic setting in MB
- only 15% effective as monotherapy
- up to 55% response rates when combined with FU and Leucovorin
*most regimens have FU delivered as a continuous intravenous infusion
Major side effects with Oxaliplatin
- Peripheral neuropathy
- Laryngeal spasm
- Cold intolerance
Oxaliplatin:
How do we manage peripheral neuropathy?
- no cold drinks or ice, wrap themselves up in winter (gloves)
- can be acute or long-term
Oxaliplatin:
How do you differentiate laryngeal spasm from anaphylaxis?
-no change in HR, BP, flushing, just strictly laryngeal spasm
Describe Raltitrexed
- thymidilate synthetase inhibitor
- metastatic setting
- equal as monotherapy or with FU/leucovorin
Raltitrexed needs to be adjusted for ____ dysfunction
renal
Describe Capecitabine
- first oral fluoropyrimdine that allows therapy to be delivered at HOME similar to infusion fluorouracil
- metabolized to FU
- adjuvant and metastatic setting
SE of Capecitabine
- hand food syndrome
- diarrhea
- stomatitis
Describe Bevacizumab
A monoclonal antibody directed against vascular endothelial growth factor (VEGF), so you don’t get blood vessels forming that feed the tumor.
Bevacizumab good for ____ colorectal cancer
metastatic
Bevacizumab effective in adjuvant therapy or neoadjuvant therapy?
neoadjuvant!
What does VEGF do?
- has been shown to promote the growth of vascular endothelial cells derived from arteries, veins, and lymphatics
- also promotes endothelial cell survival, as shown by its ability to prevent apoptosis under conditions of serum starvation
- binds to two known TK; VEGFR1 and VEGF2
List some Bevacizumab-Related Toxicities
- Grade 3/4 bleeding
- Any thromboembolism
- Grade 3 proteinuria
- Grade 3 hypertension
- Perforation
Describe Cetuximab
- A chimeric monoclonal antibody directed at cancer cells over expressing the epidermal growth factor receptor (EGFR), which is seen frequently in colorectal cancers
- monotherapy or in combo with irinotecan
SE of Cetuximab
the most common adverse effects are weakness, malaise, fever, headache and an acneiform rash
Describe Panitumumab
- Fully human EGFR antibody but with less anaphylaxis
- Multiple trials in multiple lines, with and without chemotherapy
What is the purpose of adjuvant chemotherapy?
- eliminate micro-metastases
- ideally, shortly after surgery when tumor burden is low
FUFA
Fluorouracil and Leucovorin
MAYO?
How did it compare to observation?
- fluouracil and leucovorin
- It was better than observation for overall survival
What is better: capecitabine or bolus 5-FU/LV ?
capecitabine
Describe DFS
Disease-Free Survival:
- DFS allows to make more quickly a decision regarding the efficacy of a new Tx
- Clinical trials can be completed more quickly
- Drug development time can be shortened
- Better therapy can be made available to patients more quickly
- DFS can be considered as an endpoint of its own merit in decreasing the high cost, quality of life impact and debilitating consequence of recurrent disease
What is standard adjuvant therapy for stage 3 colon cancer ?
6 months of Oxaliplatin based therapy (FOLFOX-4)
Should we give adjuvant therapy for stage 2 colon cancer?
- remains a contentious issue
- no study done so far has had enough patients to answer the question; by one estimate would need 5000-8000 patients to convincingly answer the question given current absolute risk reduction
Who should get adjuvant therapy in stage 2 colon cancer?
- no molecular low-risk features
- age < 60
- less than 9 nodes removed
- T4 tumors
- perforation
What adjuvant therapy should we use in stage 2 colon cancer if it’s indicated?
6 months of capecitabine
Adjuvant therapy for rectal cancer contains _____
radiation
Describe the adjuvant therapy for rectal cancer
-During radiation, fluorouracil with radiation + 4 months of post-op Oxaliplatin based therapy
What is the adjuvant therapy for colon and rectal cancer
1st line: FOLFOX
2nd line: Capecitabine with FU/Lev
is FOLFIRI or FOLFOX better
looks like FOLFIRI is a little better
For first line chemotherapy choice, we can either choose ______ or ______
irinotecan or oxaliplatin
Benefits of an irinotecan-based therapy
- Not associated with neuropathy
- Must be dose-reduced for hepatic dysfunction
Benefits of an oxaliplatin-based therapy
- Less alopecia, mucositis, nausea
- Safer in setting of hepatic dysfunction
What is in FOLFIRI ?
- irinotecan
- leucovorin
- fluouracil
What is in FOLFOX ?
- oxaliplatin
- leucovorin
- flourouracil
- raltitrexed
What are FOLFIRI and FOLFOX used for?
metastatic colon/rectal cancer
Side effects of oxaliplatin
neurotoxicity
- paresthesias
- cold intolerance, etc
What is the most important risk factor for persistent neurotoxicity caused by oxaliplatin ?
total cumulative dose
100% of patients experience some sensory neuropathy after 4 cycles
SE of FU
- decreases in blood cells
- n/v/d
- mouth sources
- hand food syndrome (they need to moisturize lol)
Irinotecan is less toxic with what type of administration ?
regimens that contain protracted infusion regimens of FU vs bolus FU
SE of irinotecan
DIARRHEA
Also:
- n/v
- inability to fight off infections
- hair loss
- mouth sores
- fatigue
Irinotican for metastatic or adjuvant?
metastatic
