Module 6: Colorectal Cancer

What factors will NOT increase risk of CRC?

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

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

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

what are the standard profiling of mCRC?

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

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