question

--What is the 2nd leading cause of cancer death in the US?

answer

Colorectal cancer

question

--What are the risk factors of colorectal cancer?

answer

Age - >50 y/o; Genetic factors - Familial adenomatous polyposis (FAP) and Hereditary nonpolyposis colorectal cancer (HNPCC); Pre-existing conditions - IBD, neoplastic colorectal polyps; Family hx; Diet - low fiber, excess fat, excess calories, EtOH, smoking

question

--What components of a diet can decrease risk of colorectal cancer?

answer

High fiber intake, calcium and vitamin D, NSAIDs, ASA, COX-2 inhibitors

question

--What is the proposed mechanism for fiber supplementation in colorectal cancer prevention?

answer

Decrease fecal bile acids, decrease transit time, binds to fecal mutagens, dilutes fecal material

question

--What is the proposed mechanism for dietary fat reduction in colorectal cancer prevention?

answer

Decreases fecal bile acids, reduces consumption of heterocyclic amines & other carcinogens produced through meal preparation and processing

question

--What is the proposed mechanism for calcium supplementation in colorectal cancer prevention?

answer

Direct binding to bile & fatty acids, inhibits epithelial cell proliferation

question

--What is the proposed mechanism for COX inhibition in colorectal cancer prevention?

answer

Decreases COX-2 mediated free radical formation, may inhibit growth factor synthesis in response to tumor promoters

question

--What are our screening options for colorectal cancer?

answer

Fecal occult blood test (FOBT), Fecal immunochemical test (FIT), Flex sigmoidoscopy (FSIG, q5 years) *Colonoscopy* (q10 years)

question

--When should we begin screening for colorectal cancer in someone with family history?

answer

At age 35-40

question

--When should we begin screening for colorectal cancer in someone with familial adenomatous polyposis (FAP)?

answer

At age 10-12

question

--When should we begin screening for colorectal cancer in someone with hereditary nonpolyposis colorectal cancer (HNPCC)?

answer

At age 30

question

--At what age do we typically begin screening for colorectal cancer?

answer

At age 50

question

--What is the most important independent prognostic factor for survival and disease recurrence?

answer

Stage of cancer at diagnosis

question

--What are the s/sx a/w colorectal cancer in addition to hx & PE?

answer

Change in bowel habits, blood in stool, weight loss unplanned, anorexia/GI pain

question

--In general, what are our tx options for colorectal cancer?

answer

Surgery, radiation, chemotx, targeted molecular tx

question

--In general, what can influence our treatment modality for colorectal cancer?

answer

Age, co-morbidities, performance status

question

--When are we using surgery during colorectal cancer?

answer

Stage I & II, localized dz - for curative intent Stage III & IV - generally palliative/debulking to dec bleeding, obstruction, improve quality of life

question

--When are we using radiation during colorectal cancer?**

answer

*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

question

--Overall, what is tx for local dz, stage I and II colorectal CA?

answer

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

question

--What is one of the backbones for treatment of colorectal cancer?

answer

A 5-FU (fluoropyrimidine) based regimen is the std of care

question

--Overall, what is tx for locally advanced, Stage III colorectal cancer?

answer

Surgery Adjuvant chemotherapy - 5-fluorouracil (5-FU) based regimens in standard of care

question

--Overall, what is tx for advanced dz, stage IV colorectal cancer?

answer

Chemotherapy Perhaps add'l radiation or surgery to improve palliative care

question

--What are our chemotherapy regimens in colorectal CA?

answer

FOLFOX, FOLFIRI, CapeOx, bevacizumab, cetuximab, panitumumab

question

--What are our options for neoadjuvant chemotherapy in colorectal CA?

answer

FOLFOX +/- bevacizumab FOLFIRI CapeOx

question

--What agents are part of FOLFOX regimen?

answer

5-FU, leucovorin, and oxaliplatin

question

--What is the scheduling and administration of our mFOLFOX-6 regimen?

answer

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.

question

--FOLFOX is generally given outpatient or inpatient?

answer

Outpatient after day 1 as these patients can go home with a pump

question

--5-FU should be avoided if T.bili is:

answer

>5 mg/dL

question

--What parameters would warrant contacting a provider regarding use of a FOLFOX regimen for colorectal cancer?

answer

If ANC <1.5, PLT 5, CrCl <30

question

--How should we admin hematopoietic growth factor support for FOLFOX or FOLFIRI pts?

answer

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

question

--What are the toxicities a/w FOLFOX regimen?

answer

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)

question

--When are we usually seeing hypersens rxn w/ oxaliplatin as part of FOLFOX admin?

answer

Around 6th dose; May rechallenge with low dose and direct observation

question

--What level of ematogenicity is a/w the FOLFOX regimen? Regimen for premedication?

answer

Moderate ematogenicity Day 1 = 5-HT3 antagonist + dexamethasone +/- lorazepam PRN Day 2-3 = +/- 5-HT3 antagonist and +/- lorazepam PRN

question

--How can we manage diarrhea d/2 5-FU in FOLFOX admin?

answer

Reduce dose or delay, give loperamide, IV hydrate and electrolyte replacement

question

--How can we manage mucositis d/2 5-FU in FOLFOX regimen admin?

answer

Opioids, IV hydration, nutritional support; may remove bolus 5-FU and keep the infusion

question

--Oxaliplatin is only compatible with what administration fluid?

answer

D5W

question

--What component of FOLFOX has had shortages and how can we handle?

answer

leucovorin Use levo-leucovorin or use lower doses +/- 5-FU increases

question

--What two regimens are interchangeable for colorectal cancer?

answer

FOLFOX and CapeOx

question

--What drugs are part of CapeOx regimen for colorectal cancer?

answer

oxaliplatin and capecitabine

question

--How is CapeOx admin?

answer

Day 1: oxaliplatin Day 1-14: capecitabine PO BID

question

--Patient was an IVDA and now being tx for colorectal cancer with chemotherapy, would you use FOLFOX or CapeOx?

answer

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.

question

--How are we renally adjusting for CapeOx regimen?

answer

CrCl 30-50 ml/min: 25% dose reduction CrCl <30 ml/min: use is contraindicated

question

--What kind of antiemetic tx are we using with CapeOx regimen?

answer

Day 1: 5-HT3 antagonist + dexamethasone +/- lorazepam PRN prior to oxaliplatin Day 1-14: Prochlorperazine or promethazine PO PRN

question

--What are the ADRs of CapeOx regimen?

answer

Hand-foot syndrome (d/2 capecitabine, varying grades of regional pain/blistering) Diarrhea (dose-limiting tox, ~55% of pts)

question

--What are some drug interactions with CapeOx regimen?

answer

D/2 capecitabine being a strong 2C9 inhibitor we affect *warfarin* (monitor INR) and *phenytoin* (monitor levels)

question

--What pt instructions should be given about admin of CapeOx?

answer

Take with water within 30 minutes after a meal Take approximately 12 hours apart

question

--What is the scheduling and administration of our FOLFIRI regimen?

answer

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.

question

--What agents are part of FOLFIRI regimen?

answer

5-FU, leucovorin, and irinotecan

question

--Which agent in FOLFIRI req hepatic monitoring and concerns? Why?

answer

irinotecan Irinotecan and metabolite (SN-38) higher in patients with liver metastases and hepatic dysfunction

question

--What antiemetic regimen would we use for FOLFIRI?

answer

Moderately emetogenic regimen Day 1 = 5-HT3 antagonist + dexamethasone +/- aprepitant +/- lorazepam PRN Day 2-3 = +/- 5-HT3 antagonist +/- dexamethasone +/-lorazepam PRN

question

--What are the ADRs of FOLFIRI regimen?

answer

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)

question

--What agent are we usually giving for late diarrhea (>24 h after dose)?

answer

loperamide

question

--What agent are we usually giving for early diarrhea?

answer

atropine

question

--How can we admin bevacizumab?

answer

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

question

--What are some black box warnings with bevacizumab?

answer

GI perforation, hemorrhage, wound dehiscence (can affect healing w/in 28 days of surgery or an invasive line placement, etc)

question

--What toxicities can we see w/ bevacizumab?

answer

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

question

--Which drug is most appropriate when pt has KRAS *wild-type* colorectal CA?**

answer

cetuximab (must be wild-type!!)

question

--What is the MoA of cetuximab?

answer

Chimeric monoclonal antibody Directed against EGFR & inhibits downstream signaling pathways

question

--What are the toxicities/black box with cetuximab?

answer

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)

question

--What is the MoA of panitumumab?

answer

Fully human monoclonal antibody Directed against EGFR & inhibits downstream signaling pathways

question

--How often are we admin panitumumab?

answer

q2weeks

question

--What genetic factors would indicate use of panitumumab?

answer

KRAS & NRAS *wild-type* gene only!!

question

--What are the toxicities/black box of panitumumab?

answer

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)

question

--What is the significance of BRAF mutation in colorectal cancer?

answer

Data indicates it is a strong prognostic indicator - those with this mutation do worse

question

--When are we using bevacizumab?

answer

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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