Pharmacology: Chemotherpy For GI Malignancies Flashcards
What are two common colon cancer regimens?
1) FOLFOX
- Folinic acid + 5-flurouracil + Oxaliplatin
2) FOLFIRI
- Folinic acid + 5-Flurouracil + Irinotecan
What is the median age of diagnosis of colorectal cancer?
68 yrs old
- high age since people don’t like to get colonoscopies
Median 5-yr survival age = 90% for local disease only
Median age of death = 74 yrs
Carinogenesis of colon cancer
Multiple mutations are required but usually requires the following 3 mutations:
1) genetic mutation in the adenomatous polyposis coli gene
- formation of the small benign polyp
2) activation of the K-RAS oncogene
- enlargement of the polyp
3) loss of the p53 gene functionality
- transformation to a malignant lesion
Risk factors for colorectal cancers
Age > 50
Genetics/family history
- of cancer
- of hereditary nonpolyposis colorectal cancer (lynch syndrome)
- of familiar adenomatous polyposis (FAP)
- of IBD or IBS
Smoking
Polyps
Diet/obesity/sedentary lifestyle
Eating red meat heavy, high fat, low fiber diets
Chronic alcoholism
Prevention mechanisms for colorectal cancer
1) diet and exercise
- high fiber, low fat
- high fruits/vegetables
- calcium and vitamin D supplementation
2) cyclooxygenase inhibition
- Aspirin/NSAIDs inhibit COX-2 expression which is found in 90% of colorectal cancers
this is why low dose aspirin is started for adults once they hit age 50-59 years old as long as there is no bleeding risk
Stool-based tests for colorectal cancer
Fecal occult blood testing (FOBT)
- low sensitivity and specificity
- inexpensive and non-invasive
- high false positive rates
Fecal immunochemical test (FIT)
- antibody-based to detect hemoglobin in the stool
- more expensive but more sensitive
Carcinoembryonic antigen (CEA)
Marker of choice for monitoring response to treatments for colorectal cancer
High risk factors for recurrence of colo-rectal cancer
Grade 3/4 lesions
Bowel perforation/obstruction
Lymph node involvement
Positive surgical margins
<12 lymph nodes examined
Treatment options for colorectal cancer
1) surgery via partial colectomy
- curative in localized disease (stage 1/2)
- palliative in stage 3/4
2) radiotherapy doesnt work well in colorectal cancers
- usually only used for palliative care for plain and bleeding control in colon cancers
3) chemotherapy
- is primary or adjuvant treatment
- if using surgery first, begin after 4-6 weeks from surgery
- **all regiments have folanic acid and 5-flurouracil
Common colorectal Chemotherapy toxic effects
5-FU and capecitabine
- hand-foot syndrome
- diarrhea
- mucositis
Oxaliplatin
- acute and cumulative neuropathies
Irinotecan
- diarrhea
FOLFOX regiment
- neuropathy
- neutropenia
- thrombocytopenia
FOLFIRI regiment
- fatigue
- diarrhea
- neutropenia
What needs to be checked before beginning EGFR inhibition therapy?
KRAS mutation status
- if (+) = wont respond well to EGFR therapy
if they have the wild-type mutation or no mutation = proceed with anti-EGFR treatment
How to manage acne form rash seen in EGFR- inhibitor users?
Grade 1: topical hydrocortisone/clindamycin
Grade 2: topical hydrocortisone/oral doxycycline
Grade 3/4: modify anti-EGFR dose + hydrocortisone and doxycycline and prednisone
remember the worse the rash looks, the better the drug is working
What indications are present for VEGF inhibition?
Bevacizumab
- added to 5-FU regiments for stage 4 disease
Afilbercept
- used with FOLFIRI regiments only after failing FOLFOX regiments
Ramucirumab
- used only with FOLFIRI
How does BRAF mutations affect therpies for cancer?
Help tumors to bypass inhibition of EGFR-inhibitors
in stage 4 cancers especially, but really any time you want to add anti-EGFR therapies to regiments, you should genotype for BRAF mutations
Advantages and disadvantages of neoadjuvant chemotherapy in metastatic disease
Advantages:
- control of micro-Mets
- helps determine responsiveness to chemotherapy
- avoidance of local therapy
Disadvantages
- potentially miss window of opportunity for resection
- risk of steatohepatitis
- risk hepatotoxicity
neoadjuvant therapy should only be used for 2-3 months
