Module 6: Colorectal Cancer

What factors will NOT increase risk of CRC?

* NSAIDs, ASA, COX-2 inhibitors

How fiber supplementation will decrease CRC risk?

* dec. fecal bile acids, transit time
* bind to fecal mutagens
* dilute fecal material

(SIMILAR TO dietary fat reduction)

COX inhibition benefits CRC risk reduction by how?

* dec. COX-2 mediated free radical formation
* @@inhibit GF system in response to tumor promoters@@

can CRC be cured in stage I and II?

Yes, CRC can be curative with surgery at stage I and II (stage III?)

Radiation is highly effective in CRC?

TRUE

which of the following is NOT SEs of 5-FU

* Myelosuppression (DLT bolus), Diarrhea (DLT CI)
* Mucositis
* **Neuropathy (common se of oxaliplatin)**
* Photosensitivity
* Hand Foot (DLT CI): 2-4 weeks of therapy
* Rash.
* Diarrhea: management with Loperamide

What is NOT good advice for pt with HFS?

do exercise

* SHOULD do:
* avoid anything that is heat-stimuli: hot water, constrictive foot wear
* WEAR thick cotton gloves or socks: to keep them lubricated
* apply Vaseline or emollient

Where is thymidine phosphorylase commonly found?

in tumor cells

* catalyze the reaction to activate 5-FU

how Capecitabine is related to 5-FU

* Cap = oral form of 5-FU
* undergoes a 3-step conversion to 5-FU

What are the most common SEs with Capecitabine?

* diarrhea: dosing limit toxicity
* HFS

which medications can increase Cap. concentration?

Phenytoin

Antacid

What is the role of Leucovorin in 5-FU activity?

**synergizes with 5-FU** to increase 5-FU cytotoxicity by acting on CH2THF, which promotes TF inhibition, further leads to DNA damage

What are BBW side effects on Irinotecan?

**Diarrhea** (can give Loperamide 4mg for first loose stool, followed by 2mg q2hr until diarrhea free for 12 hours)

**Severe myelosuppression**

* Other SEs:
* alopecia
* dehydration (might be from diarrhea)
* asthenia
* N/V

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Which are the most significant SEs of Oxaliplatin?

@@Neuropathies (acute and chronic)@@

Hepatotoxicity

Myelosuppression

(other: anaphylaxis, myelosuppression, fatigue, diarrhea, mucositis)

when we should avoid 5-FU administration?

in pts with DPYD poor phenotype

→ try to define the genotypes of DPD through pre-emptive screenings

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Which medication is an antidote for 5-FU’s toxicity?

Vistogard

* works by getting converted to UMP which competitively inhibits cell damage and cell death caused by 5-FU

which phenotype is associated with higher risk of neutropenia and diarrhea with Irinotecan?

UGT1A1\*28

what are cornerstone treatments of CRC stage I to III?

FOLFOX: 5FU, Leucovorin, and Oxaliplatin

CAPEOX: Capecitabine + Oxaliplatin @@(Oral after day 1)@@

5-FU/LV

Do we need to give Adjuvant Che for stage I and low-risk stage II?

No

* only for high-risk stage II: with FOLFOX, CAPEOX or 5-FU
* stage III: 6 mo 6 months with FOLFOX or CapeOx
* (can use **single**-agent Capecitabine or 5FU/LV in **select patients**)

what are the features of stage II high risk?

T4 tumor: penetrate deeper into adjacent organs or structures

Poorly differentiated histology

<12 nodes examined

When should we initiate adjuvant chemo?

as soon as pt is medically able

* each 4 week delay = 14%decrease in OS
* 6-8 weeks post surgery

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what are the standard profiling of **m**CRC?

RAS

RAF

MSI or MMR

Where are the most common metastatic sites of mCRC?

liver, lung, bone

* pt with a resectable primary tumor AND resectable synchronous metastases may be cured

what is the frontline therapy for **stage IV**?

FOLFOX or FOLFIRI

* (**irinotecan replaced oxaliplatin**, same drugs as IFL)

\-+/- biologic agents (Bevacizumab)

* $Remember: NO irinotecan or biologic agents in stage I -III$

Can we use Cetuximab or Panitumumab in mutant KRAS?

NO

* just for wt-KRAS

what are the SEs of Cetuximab?

Hypersensitivities, Electrolyte imbalances, acneiform rash $(rash=survival)$.

* tell pts to use colloidal oatmeal lotion
* take short showers with lukewarm water and unscented soaps, and moisture after bathing
* keep fingernails and toenails clean and trimmed, avoid tight-fitting shoes
* wear gloves to wash dishes

NO benzoyl peroxide

what class of drug Bevacizumab belongs to?

anti-VEGF Mab

→ SEs: arteriothrombotic events: VTE, DV, HTN, proteinuria, wound healing complications (GI perforations), bleeding, HA

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what combination shouldn’t be used in stage IV CRC?

CAPIRI

what important CP of Regorafenib?

take with a low-fat breakfast

what are immunotherapy agents are approved for CRC stage IV?

Pembrolizumab

Nivolumab + Ipilimumab

* can be used either of them as long as MSI-H or dMMR is present