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
How does the side of the primary tumor side affect possible treatment?
Right sided tumor = give anti-VEGF treatment vs anti-EGFR
- VEGF > EGFR
Left sided tumor = give anti-EGFR treatment vs anti-VEGF treatment
- EGFR > VEGF
What sided of primary tumors should patients be offered cetuximab or panitumumab for first line treatment?
Left-sided
What is the treatment for relapsed stage 4 colorectal cancer?
Regorafenib 160mg PO daily
Is a multikinase inhibtor
Is second line and in only in patients who have failed chemotherapies
has really bad side effects (hand-foot reaction, hepatotoxicity, extreme HTN)
What do you do if hypersensitivity with oxaliplatin occurs?
STOP treatment and give diphenhydramine, steroids, IV fluids, epi and albuterol
how does oxaliplatin cause neurotoxicity?
Chelates magnesium and calcium ions which casues hyper-excitable sodium channels in neurons
How do you manage irinotecan-induced diarrhea?
Acute = atropine
Delayed = IV fluids and electrolytes w/ possible loperamide
