Pharmacotherapy 6- Colorectal Cancer – Flashcards
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--What is the proposed mechanism for dietary fat reduction in colorectal cancer prevention?
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Decreases fecal bile acids, reduces consumption of heterocyclic amines & other carcinogens produced through meal preparation and processing
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--What is the proposed mechanism for calcium supplementation in colorectal cancer prevention?
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Direct binding to bile & fatty acids, inhibits epithelial cell proliferation
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--What is the proposed mechanism for COX inhibition in colorectal cancer prevention?
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Decreases COX-2 mediated free radical formation, may inhibit growth factor synthesis in response to tumor promoters
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--What are our screening options for colorectal cancer?
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Fecal occult blood test (FOBT), Fecal immunochemical test (FIT), Flex sigmoidoscopy (FSIG, q5 years) *Colonoscopy* (q10 years)
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--When should we begin screening for colorectal cancer in someone with family history?
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At age 35-40
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--When should we begin screening for colorectal cancer in someone with familial adenomatous polyposis (FAP)?
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At age 10-12
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--When should we begin screening for colorectal cancer in someone with hereditary nonpolyposis colorectal cancer (HNPCC)?
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At age 30
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--At what age do we typically begin screening for colorectal cancer?
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At age 50
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--What is the most important independent prognostic factor for survival and disease recurrence?
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Stage of cancer at diagnosis
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--What are the s/sx a/w colorectal cancer in addition to hx & PE?
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Change in bowel habits, blood in stool, weight loss unplanned, anorexia/GI pain
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--In general, what are our tx options for colorectal cancer?
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Surgery, radiation, chemotx, targeted molecular tx
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--In general, what can influence our treatment modality for colorectal cancer?
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Age, co-morbidities, performance status
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--When are we using surgery during colorectal cancer?
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Stage I & II, localized dz - for curative intent Stage III & IV - generally palliative/debulking to dec bleeding, obstruction, improve quality of life
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--When are we using radiation during colorectal cancer?**
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*Well established for rectal cancer, no definitive role in colon cancer*; Neoadjuvant use in rectal CA improves regional control of dz; Radiation is best with chemotx in rectal cancer; Used for palliation for pain & control of bleeding in colon cancer
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--Overall, what is tx for local dz, stage I and II colorectal CA?
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Generally surgery alone, careful surveillance w/ discretionary freq screening; Question about the role of adjuvant chemotherapy in stage II --High risk patients/more aggressive cases
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--What is one of the backbones for treatment of colorectal cancer?
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A 5-FU (fluoropyrimidine) based regimen is the std of care
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--Overall, what is tx for locally advanced, Stage III colorectal cancer?
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Surgery Adjuvant chemotherapy - 5-fluorouracil (5-FU) based regimens in standard of care
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--Overall, what is tx for advanced dz, stage IV colorectal cancer?
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Chemotherapy Perhaps add'l radiation or surgery to improve palliative care
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--What are our chemotherapy regimens in colorectal CA?
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FOLFOX, FOLFIRI, CapeOx, bevacizumab, cetuximab, panitumumab
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--What are our options for neoadjuvant chemotherapy in colorectal CA?
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FOLFOX +/- bevacizumab FOLFIRI CapeOx
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--What agents are part of FOLFOX regimen?
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5-FU, leucovorin, and oxaliplatin
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--What is the scheduling and administration of our mFOLFOX-6 regimen?
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On Day 1: 5-FU bolus, leucovorin, and oxaliplatin Then, after bolus of 5-FU we hang a bag of 5-FU and infuse over 46 hours.
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--FOLFOX is generally given outpatient or inpatient?
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Outpatient after day 1 as these patients can go home with a pump
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--5-FU should be avoided if T.bili is:
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>5 mg/dL
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--What parameters would warrant contacting a provider regarding use of a FOLFOX regimen for colorectal cancer?
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If ANC <1.5, PLT 5, CrCl <30
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--How should we admin hematopoietic growth factor support for FOLFOX or FOLFIRI pts?
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If pts counts are continually dropping and interfering with admin of regimen, but we aren't giving these factors upfront like we would with something like an AC regimen
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--What are the toxicities a/w FOLFOX regimen?
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Peripheral neuropathy (d/2 oxaliplatin, avoid cold exposure/objects during & ~48 hrs s/p admin); Hypersensitivity (d/2 oxaliplatin, won't premedicate); Diarrhea (d/2 5-FU); Mucositis (d/2 5-FU)
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--When are we usually seeing hypersens rxn w/ oxaliplatin as part of FOLFOX admin?
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Around 6th dose; May rechallenge with low dose and direct observation
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--What level of ematogenicity is a/w the FOLFOX regimen? Regimen for premedication?
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Moderate ematogenicity Day 1 = 5-HT3 antagonist + dexamethasone +/- lorazepam PRN Day 2-3 = +/- 5-HT3 antagonist and +/- lorazepam PRN
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--How can we manage diarrhea d/2 5-FU in FOLFOX admin?
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Reduce dose or delay, give loperamide, IV hydrate and electrolyte replacement
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--How can we manage mucositis d/2 5-FU in FOLFOX regimen admin?
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Opioids, IV hydration, nutritional support; may remove bolus 5-FU and keep the infusion
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--Oxaliplatin is only compatible with what administration fluid?
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D5W
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--What component of FOLFOX has had shortages and how can we handle?
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leucovorin Use levo-leucovorin or use lower doses +/- 5-FU increases
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--What two regimens are interchangeable for colorectal cancer?
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FOLFOX and CapeOx
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--What drugs are part of CapeOx regimen for colorectal cancer?
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oxaliplatin and capecitabine
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--How is CapeOx admin?
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Day 1: oxaliplatin Day 1-14: capecitabine PO BID
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--Patient was an IVDA and now being tx for colorectal cancer with chemotherapy, would you use FOLFOX or CapeOx?
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Don't want to send them home with that IV port that will be available if we choose FOLFOX, so CapeOx would be the better option and protect patient's safety.
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--How are we renally adjusting for CapeOx regimen?
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CrCl 30-50 ml/min: 25% dose reduction CrCl <30 ml/min: use is contraindicated
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--What kind of antiemetic tx are we using with CapeOx regimen?
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Day 1: 5-HT3 antagonist + dexamethasone +/- lorazepam PRN prior to oxaliplatin Day 1-14: Prochlorperazine or promethazine PO PRN
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--What are the ADRs of CapeOx regimen?
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Hand-foot syndrome (d/2 capecitabine, varying grades of regional pain/blistering) Diarrhea (dose-limiting tox, ~55% of pts)
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--What are some drug interactions with CapeOx regimen?
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D/2 capecitabine being a strong 2C9 inhibitor we affect *warfarin* (monitor INR) and *phenytoin* (monitor levels)
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--What pt instructions should be given about admin of CapeOx?
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Take with water within 30 minutes after a meal Take approximately 12 hours apart
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--What is the scheduling and administration of our FOLFIRI regimen?
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On Day 1: 5-FU bolus, leucovorin, and irinotecan Then, after bolus of 5-FU we hang a bag of 5-FU and infuse over 46 hours.
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--What agents are part of FOLFIRI regimen?
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5-FU, leucovorin, and irinotecan
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--Which agent in FOLFIRI req hepatic monitoring and concerns? Why?
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irinotecan Irinotecan and metabolite (SN-38) higher in patients with liver metastases and hepatic dysfunction
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--What antiemetic regimen would we use for FOLFIRI?
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Moderately emetogenic regimen Day 1 = 5-HT3 antagonist + dexamethasone +/- aprepitant +/- lorazepam PRN Day 2-3 = +/- 5-HT3 antagonist +/- dexamethasone +/-lorazepam PRN
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--What are the ADRs of FOLFIRI regimen?
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Mucositis (d/2 5-FU, removal of bolus with high grades); Diarrhea (d/2 5-FU and irinotecan, usually giving atropine for early onset/prevention)
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--What agent are we usually giving for late diarrhea (>24 h after dose)?
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loperamide
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--What agent are we usually giving for early diarrhea?
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atropine
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--How can we admin bevacizumab?
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Usually give with 5-FU Standard administration --1st dose over 90 minutes, 2nd dose over 60 minutes, subsequent doses over 30 minutes Rapid infusion bevacizumab --5 mg/kg IV over 10 minutes; 10 mg/kg IV over 20 minutes; 15 mg/kg IV over 30 minutes
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--What are some black box warnings with bevacizumab?
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GI perforation, hemorrhage, wound dehiscence (can affect healing w/in 28 days of surgery or an invasive line placement, etc)
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--What toxicities can we see w/ bevacizumab?
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HTN (max 140/90 to admin, if uncontrolled then temp d/c, in crisis d/c); Proteinuria/nephrotic syndrome (req urine protein eval every admin); Thromboembolism
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--Which drug is most appropriate when pt has KRAS *wild-type* colorectal CA?**
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cetuximab (must be wild-type!!)
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--What is the MoA of cetuximab?
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Chimeric monoclonal antibody Directed against EGFR & inhibits downstream signaling pathways
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--What are the toxicities/black box with cetuximab?
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Infusion-related hypersensitivity (pre-med with diphenhydramine/etc); Cardiopulm arrest (very rare, but serious); Acneform rash (↑ correlates with survival/response however, tx w/ Abx/CSs); Hypomagnesemia (common)
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--What is the MoA of panitumumab?
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Fully human monoclonal antibody Directed against EGFR & inhibits downstream signaling pathways
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--How often are we admin panitumumab?
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q2weeks
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--What genetic factors would indicate use of panitumumab?
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KRAS & NRAS *wild-type* gene only!!
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--What are the toxicities/black box of panitumumab?
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Infusion-related hypersensitivity; Dermatologic toxicity (reported in majority of pts, severe in ~12%); Diarrhea (incidence dec w/ combo tx); Electrolyte depletion (calcium and magnesium); Pulmonary fibrosis (rare, perm d/c if lung abnormalities develop)
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--What is the significance of BRAF mutation in colorectal cancer?
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Data indicates it is a strong prognostic indicator - those with this mutation do worse
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--When are we using bevacizumab?
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With fluoropyrimidine-based chemotherapy as initial therapy for metastatic disease. It is considered standard of care and provides a survival benefit as compared with combination chemotherapy alone
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