30 - Colon & Rectal Cancer Flashcards
1
Q
Colorectal cancer risk factors
A
- Risk of developing colorectal cancers usually begins at age 40 and increases w/ age (mean age at presentation = 70 y/o)
- Risk factors = age, family hx, alcohol intake, diet (high in red meats and processed meats, low in fresh fruits and vegetables), smoking, obesity, IBD
2
Q
Pathophysiology of colon and rectal cancer
A
- More than 95% of primary colorectal cancers are adenocarcinomas (tend to be more responsive to chemotherapy and radiation)
- Colon cancer 3x as common as rectal cancer
- Rectal cancer defined as arising below the peritoneal reflection or < 12 cm from the anal verge
- Colorectal adenocarcinomas tend to remain superficial for a long time, slowly invading the deeper layers of the intestinal wall
- As lesion progresses, there is extension through the bowel wall into the pericolonic fat
3
Q
Signs and sx of colon and rectal cancer
A
- Change in bowel habits
- Tenesmus (continual or recurrent urge to vacate the bowels)
- Diarrhea or constipation
- Blood in stool
- Narrow stools
- Abdominal discomfort and gas pains
- Weight loss
4
Q
Screening and staging of colon and rectal cancer
A
- Recommend continuous screening b/c if the cancer is caught at the early stages there is a much greater chance of survival and lower risk of recurrence
- Stool-blood guaiac test detects presence of blood in the stools
- Sigmoidoscopy (useful visualizing sigmoid colon as well as for taking a biopsy specimen)
- Barium enema (high false negatives possible, thus should be reserved as complement to a scope)
- Colonoscopy
- Carcinoembryonic antigen (CEA) -> not 100% specific, so elevation can be present w/ no colorectal cancer; useful as a marker to find out if therapy is working in diagnosed cancer; should normalize after surgery once cancer is removed
5
Q
Benefits of screening for colorectal cancer
A
- Effective to detect pre-cancerous, early stage or small cancers among people who don’t show signs or sx of cancer
- Decreases the px risk from dying of cancer
- Canadian guidelines call for all people age 50 and older to be evaluated annually or biennially w/ fecal occult blood testing (FOBT) unless pt is at high risk for colorectal cancer
6
Q
Tx options for colorectal cancer
A
- Surgery -> primary curative procedure for px w/ stage 1-3 disease; surgical resection of the bowel (ex: hemicolectomy or abdominoperineal resection)
- Resection of isolated liver and/or lung metastases
- Radiation
- Rectal carcinomas are associated w/ a local recurrence rate much higher than colon cancers
- Adjuvant radiation to the tumour 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 sx
7
Q
Staging of colorectal cancer
A
- Stage 1 = local disease, no invasion of muscular mucosa
- Stage 2 = invasion of muscular mucosa, no extracolonic spread
- Stage 3 = lymph node involvement
- Stage 4 = metastatic disease
- Sites of metastases = liver, lung, bone
8
Q
When is chemotherapy used for colorectal cancer?
A
- Used in adjuvant setting after surgical resection of stage 2 and 3 cancer
- Despite the high rate of resectability, almost ½ of all px w/ colorectal cancer will recur b/c of residual disease not apparent at the time of surgery (primary reason for adjuvant therapy)
- Primary therapy of metastatic colon and rectal cancers
9
Q
Fluorouracil for colorectal cancer
A
- Most extensively studied and used agent in colorectal cancer
- Used in both adjuvant and metastatic setting
- Pattern of toxicity differs between bolus administration and continuous infusion
- Grade 3 & 4 hematological toxicity is more common w/ the bolus regimens, whereas the infusion regimens are more likely to show “hand-foot” syndrome (palmar-plantar erythrodysethesia)
- Essential component of selected irinotecan or oxaliplatin regimens
10
Q
Hand-foot syndrome
A
- Painful reddening of the skin that can proceed to desquamation
- Px should be counselled to report any changes to palms and soles ASAP
- Prevention measures include moisturizing liberally and avoiding sources of heat and friction
- Tx measures can include topical anesthetics, application of cold, oral analgesics
11
Q
Irinotecan for colorectal cancer tx
A
- Topoisomerase 1 inhibitor
- Used in metastatic setting
- Has activity as a single agent in px w/ fluorouracil-resistant disease
- Currently first line agent for tx of metastatic colorectal cancer in combo w/ fluorouracil and leucovorin
- Real problem w/ diarrhea (early onset, < 24 h, & late onset, 3-5 days after tx)
- Give a dose of atropine just before starting irinotecan to prevent early onset diarrhea (early onset is muscarinic in nature, late onset isn’t)
- Can use loperamide for late onset
12
Q
Describe the dosing for loperamide for irinotecan-induced diarrhea
A
- Take 4 mg at first onset of water stools, then 2-4 mg every 2 h until 12 h w/ no bowel movement, up to 32 mg/day
- Most px don’t reach max daily dose but it is safe from them to take max daily dose for 2-3 days, then they should contact their oncologist
13
Q
Oxaliplatin for colorectal cancer tx
A
- Currently approved in both adjuvant and metastatic setting
- Better response rates when combined w/ fluorouracil and leucovorin; most regimens have fluorouracil delivered as a continuous IV infusion
- Major AE = peripheral neuropathy, laryngeal spasm, and cold intolerance
14
Q
Raltitrexed for colorectal cancer tx
A
- Thymidilate synthetase inhibitor
- Currently approved in metastatic setting
- Deaths in Europe secondary to lack of dose reductions in px w/ renal dysfunction (so hardly used now)
15
Q
Capecitabine for colorectal cancer tx
A
- First oral fluoropyrimidine that allows therapy to be delivered at home similar to IV fluorouracil
- Metabolized to fluorouracil (greater metabolism in cancer cells than normal cells)
- Used in both adjuvant and metastatic setting
- Designed to take BID for 2 weeks w/ 1-week break (cycle = 3 weeks)
- If pt doesn’t take a break, can get serious diarrhea and hand-foot syndrome
16
Q
Bevacizumab for colorectal cancer tx
A
- MAb directed against vascular endothelial growth factor
- Shown to be efficacious in metastatic colorectal cancer; not shown to be effective in adjuvant therapy
- Toxicities -> increases risk of HTN, thromboembolism
17
Q
Cetuximab for colorectal cancer tx
A
- Chimeric MAb directed at cancer cells overexpressing the EGF receptor (EGFR), which is frequently seen in colorectal cancers
- Has been studied as monotherapy in metastatic colorectal cancer, as well as in combo w/ irinotecan
- Most common AE = weakness, malaise, fever, headache, rash
18
Q
Principles of adjuvant tx for colorectal cancer
A
- Recurrence generally can’t be cured
- Goal of adjuvant = eliminate micro-metastases
- Ideally given shortly after surgery when tumour burden is low
- For someone to be well enough to receive chemotherapy, must have neutrophils above 1-1.5 * 10^9/L, must have platelets above 100 * 10^9, and must have normal Hgb
19
Q
Adjuvant therapy for stage 3 colon cancer
A
6 months of oxaliplatin based therapy (FOLFOX-4) -> but apparently FOLFOX-4 isn’t used anymore so just use FOLFOX-6?; FOLFOX-6 = simplified version of FOLFOX-4
20
Q
Which px w/ stage 2 colon cancer should receive adjuvant therapy? Which regimen is recommended?
A
- No molecular low-risk features
- Age < 60 y/o
- < 9 nodes removed
- T4 tumours
- Perforation
- Should use 6 months of capecitabine
- Can also use fluorouracil therapy, based on pt preference?
21
Q
Adjuvant therapy for rectal cancer
A
- During radiation, fluorouracil 200 mg/m2/day
- Plus 4 months post-op oxaliplatin based therapy
- FOLFOX-6
22
Q
Adjuvant therapy in stage 3 and high-risk stage 2 colon and rectal cancer
A
- *FOLFOX-4 protocol
- Oxaliplatin IV over 2 h (day 1) + concurrent w/ leucovorin IV (day 1 and 2)
- Followed by fluorouracil IV bolus (day 1 and 2) followed by fluorouracil continuous IV infusion over 22 h (day 1 and 2)
- Repeated every 14 days x 12 cycles
- Alternate = capecitabine 2000-2500 mg/m2/day orally divided into 2 doses daily x 14 days -> repeated every 21 days for 8 cycles
- Degramont protocol -> leucovorin IV (day 1 and 2), followed by fluorouracil IV bolus (day 1 and 2), followed by fluorouracil continuous IV infusion over 22 h (day 1 and 2) -> repeated every 14 days x 12 cycle (same as FOLFOX-4 but no oxaliplatin)
23
Q
First line chemotherapy choice – irinotecan vs. oxaliplatin
A
- Choice of therapy depends on toxicity, as no single regimen is clearly superior
- Irinotecan-based -> not associated w/ neuropathy; must reduce dose for hepatic dysfunction
- Oxaliplatin-based -> less alopecia, mucositis, N; safer in setting of hepatic dysfunction
- In MB, irinotecan is first line (FOLFIRI), then oxaliplatin (FOLFOX-6) is used if refractory b/c oxaliplatin has severe neurotoxicity
24
Q
FOLFIRI regimen for metastatic colon/ rectal cancer
A
- Irinotecan IV over 2 h (day 1) concurrent w/ leucovorin IV (day 1), followed by fluorouracil IV bolus (day 1) followed by fluorouracil continuous IV infusion over 46 h -> repeated every 14 days
- Px can also get bevacizumab added to this regimen at least 4-8 weeks after surgery (generally given before irinotecan)
- Bevacizumab AE = hypertension, proteinuria, perforation
25
Q
FOLFOX-6 regimen for metastatic colon/ rectal cancer
A
Oxaliplatin IV over 2 h (day 1) concurrent w/ leucovorin IV (day 1), followed by fluorouracil IV bolus (day 1), followed by fluorouracil continuous IV infusion over 46 h -> repeated every 14 days
26
Q
Describe acute oxaliplatin neurotoxicity
A
- Precipitated by cold exposure
- Paresthesia, dysesthesia, muscle cramping
- Rare = pharyngolaryngeal dysesthesia (throat discomfort and tightness, sensation of inability to breathe or swallow)
- Onset = 2-48 h (can last longer w/ more tx)
- Rapid and complete recovery
27
Q
Describe persistent oxaliplatin neurotoxicity
A
- Paresthesia, dysesthesia, hypoesthesia
- Affects fingertips and toes then hands and feet
- More common as px have more cycles of therapy
- Interferes w/ daily activities; increases in duration and intensity
- Onset = > 14 days
28
Q
What is the most important risk factor for oxaliplatin neurotoxicity?
A
Total cumulative dose (100% of px experience some sensory neuropathy after 4 cycles)
29
Q
Fluorouracil SE
A
- Dependent on how the agent is being administered
- SE = decreases in blood cells, N/V/D, mouth sores, hand-foot syndrome
- Can get them to suck on ice chips/popsicle to reduce mouth sores (thought is that the cold will cause vasoconstriction; can’t do this w/ oxaliplatin b/c of intolerance to cold)
30
Q
Irinotecan SE
A
- More favourable toxicity profile w/ regimens that contain protracted infusional regimens of fluorouracil vs. bolus fluorouracil
- Real problem w/ diarrhea (early and late onset)
- Generally, a prophylactic dose of atropine will almost eliminate occurrence of early onset diarrhea
- Other SE = N/V, inability to fight off infections, hair loss, mouth sores, fatigue
