Colorectal Cancer Flashcards by Kim Nguyen

Treatment considerations for CRC

Stage of disease
Age of patient
Comorbidities
Pharmacogenomics: KRAS wild-type, MSI status
Metastatic setting: previous treatments used, toxicity profiles of various chemo regimens

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General principles of CRC treatment: chemo in adjuvant setting

5-FU-based regimens are the standard of care

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General principles of CRC treatment: surgery

Treatment of choice in patients with potentially curable disease

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How many lymph nodes must be samples to determine node positive or negative disease?

At least 12

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CRC treatment based on stage: Stage I

no adjuvant chemo; surgery and monitoring

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CRC treatment based on stage: Stage II

no treatment OR adjuvant chemo based on risk factors

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CRC treatment: Stage IIA, no high-risk factors

consider adjuvant chemo, clinical trial, or observation

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CRC treatment: Stage IIB or C

adjuvant chemo or observation

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Adjuvant chemo options in CRC

single-agent capecitabine or 5-FU/leucovorin for low risk; FOLFOX or CAPEOx for high risk

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FOLFOX components

5-FU, leucovorin, oxaliplatin

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CAPEOx components

Capecitabine, oxaplatin

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CRC treatment: Stage III

adjuvant chemo

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What shouldn’t be used in the adjuvant setting in CRC?

Targeted therapies, irinotecan

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Stage III CRC adjuvant regimens

FOLFOX q2w x12 cycles
CapeOx: 6 months for high-risk; 3 months for low-risk
RT and capecitabine/5-FU used pre-op for rectal cancer
FOLFOX and CapeOx are superior to 5-FU/leucovorin in Stage III
If oxaliplatin toxicity is intolerable, dose-adjust or remove from the regimen after 3-4 months of therapy or sooner if neurotoxicity is grade 2 or higher

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CRC treatment: Stage IV

Chemo, targeted therapy, immunotherapy

Surgery is NOT primary treatment

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Stage IV CRC: resectable liver only or lung-only metastases

Surgical excision along with synchronous resection of liver or lung metastases, followed by adjuvant chemo with FOLFOX or CapeOx (preferred)

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Stage IV CRC: regimen options

FOLFIRI, CapeOx, or FOLFOX +/- bevacizumab
(D/C bevacizumab at least 4 weeks prior to surgery)

FOLFIRI or FOLFOX +/- panitumumab or cetuximab if KRAS wildtype

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Stage IV CRC: unresectable liver or lung-only lesions

Chemo, evaluate disease q2months to determine respectability and/or lung metastases

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CRC: Anti-HER2 therapy

Now recommended as subsequent therapy options in patients with tumors that are RAS/BRAF wild-type and have HER2 overexpression

Anti-HER2 regimens

Trastuzumab + [pertuzumab or lapatinib] (initial or subsequent line)
Fam-trastuzumab deruxtecan (subsequent line)

CRC: BRAF mutation treatment

Doublet therapy: second or third-line treatment
Cetuximab 250 mg/m2 IV qweek + Encorafenib 300mg PO QD

5-FU and leucovorin AEs

Bolus: myelosuppression
Continuous infusion: hand-foot syndrome, diarrhea, mucositis

Capecitabine is the prodrug for what?

5-FU

Capecitabine AEs

Dose-limiting

Hyperbilirubinemia
Diarrhea
Hand-foot syndrome
Mucositis

Capecitabine is CI'ed in what?

DPD deficiency

Capecitabine dose adjustments

CrCl 30-50ml/min: 25% reduction <30: CI'ed

Capecitabine DDI

2C9 inhibitor; watch out with warfarin and phenytoin

Oxaliplatin AEs

Peripheral neuropathy **Cold intolerance/sensitivity** Myelosuppression

Oxaliplatin cold sensitivity management

Eating/drinking at room temperature GABA analogues, but poor efficacy SNRIs like duloxetine

Irinotecan AEs

DIARRHEA Fatigue Alopecia Myelosuppression/neutropenia

Irinotecan-induced diarrhea management

Acute: atropine or diphenoxylate atropine Delayed: loperamide

Bevacizumab, Ziv-aflibercept, ramucirumab AEs

HTN Delayed wound healing → D/C 4 weeks before surgery, restart 4 weeks after Proteinuria Hemorrhage Arterial thrombosis Diarrhea Neutropenia

Cetuximab, panitumumab AEs

Infusion reactions: premedicate! Hypomagnesemia Paronychia **Acneiform rash**

EGFR inhibitor acneiform rash management

Limit sun exposure, wear sunscreen Avoid overdrying the skin, avoid hot baths Moisturize! Avoid OTC acne products

Criteria to use EGFR inhibitor

KRAS wild-type

Regorafenib BBW

hepatotoxicity

Regorafenib AEs (common)

fatigue, anorexia/weight loss, hand-foot syndrome, diarrhea, mucositis, infection, HTN

Regorafenib DDI

3A4 inhibitors and inducers

Trifluridine and tipiracil AEs (Lonsurf)

Anemia Neutropenia Fatigue N/V Thrombocytopenia Decreased appetite Diarrhea Abdominal pain

Lonsurf dose adjustments

Reduce dose and/or hold doses as clinically indicated if there is severe myelosuppression

Lonsurf administration

Take within 1 hour of the end of breakfast and dinner

Pembrolizumab, nivolumab AEs

Colitis Rash Hepatitis Nephritis Pneumonitis Thyroid disorders

Pembrolizumab, nivolumab indication

MSI-H tumors only in Stage IV disease

EGFRi acneiform rash: grade 1

No dose changes General precautions/nonpharm care Topical clindamycin 2% +/- hydrocortisone 1%

EGFR acneiform rash: grade 2

Topical clindamycin 2% +/- hydrocortisone 1% Minocycline BID or doxycycline BID

EGFR inhibitor rash: grade 3

Hold treatment until grade 2 Dose reduce if 2nd or 3rd incident; D/C if 4th occurrence

EGFR inhibitor rash: grade 4

D/C drug, systemic treatment with PO retinoids, IV steroids, ABX, and hydration