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PHM 703: Crit Care/Heme/Onc > Onco 2: cancer in the poo tube > Flashcards

Onco 2: cancer in the poo tube Flashcards

1
Q

risk factors for colorectla cancer

A
  • Hx of polyps
  • IBD
    • UC
    • Chron’s
    • Chronic inflammation
  • Family hx and genetics
    • FAP : much much adenomatous polyps
    • HNPCC/Lynch syndrome): mutations in DNA msmatch repair genes
  • Smoking
  • Heavy EtOH use
  • Physical inactiivty
  • Low socioeconomic status
  • Diabetes
  • Increasing age
  • Race
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1
Q

presentation of colorectal cacner

A

usually no symptoms early on in disease progression

  • Bright red or dark blood in stool, anemia
  • Change in frequency of bowel movements
  • Constipation or feeling that bowel doesn’t empty completely
  • Stool narrow than usualy
  • General abdominal discomfort (frequent gas pains, bloating, and/or cramps)
  • Wt loss with no known reason
  • Constant fatigue
  • N/V
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2
Q

gold sstandard for screening

A

colonoscopy
- start at age 45 for most people
- earlie in high risk
- Decision to screen in older pts should be individualized

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3
Q

colorectal chemo consdierations

A

we want good performing pts for chemo otherwise we might be doing more harm than good

  • stage of disease
  • performance status
  • co-morbidities
  • genomics
  • if metastatic: previous agents used
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4
Q

favorable pronostic factors for colorectal cancer

A
  • early disease: stage I-II
  • grade 1-2 lesions
  • no angiolymphatic invasion
  • nevative margins
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5
Q

unfavorable prognositc factors for colorectal cncer

A
  • advanced disease : stage III-IV
  • grade 3-4 lesioins
  • signet-ring cell or mucnous
  • lyphovascular invasion
  • positive margins
  • bowel obstruction/perforation
  • T4 disease
  • performance status
  • lymph node involvement > 4
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6
Q

stage I colocrectal treament

A

surgery alone, no adjuvant chemo

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7
Q

stage II colocrectal treament

A

Surgery +/- adjuvent cehmo (high risk stage II may benefit but no real data atm)
- if giving chemo, capecitabine preferred (can also do FOLFOX or CapeOx)

high risk
- < 12 lymph nodes examined
- Poorly differentiated histology (grade 3-4)
- Lymphovascular invasion
- Bowel obstruction
- Localized perforation
- Positive margins

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8
Q

5-FU metabolism

A

metabolized by DPD (rate limiting)
- some pts can be deficient in DPD (2 nonfunctional copies) -> life threatening tox -> avoid

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8
Q

5-FU MOA

A

breaks down into fDUMP -> inhibit thymidylate synthase -> inhibit DNA synthess

give with leucovrin (folinic acid) -> stabilies fDUMP

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9
Q

5-FU ADR

A

slow infusion -> ADR more tolerable and reduced myelosuppression
- still some hand-foot syndrome, diarrhea, and mucositis though

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10
Q

FOLFOX

A
  • folinic acid
  • 5-FU
  • oxaliplatin
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11
Q

FOLFIRI

A
  • folinic acid
  • 5-FU
  • irinotecan

neoadjuvant only, not adjuvant

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12
Q

FOLFOXIRI

FOLFIRINOX

A
  • folinic acid
  • 5-FU
  • oxaliplatin
  • irinotecan

the differene (per NiH i guess?) is that FOLFIRINOX has a higher dose of irinotecan and a bolus 5-FU

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13
Q

CapeOx

A
  • capecitabine
  • oxaliplatin
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14
Q

capecitabine MOA

A

it’s a 5-FU prodrug

can also be used as a radio-sensitizer (makes people more sensitive to raidation)

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15
Q

capecitabine admn

A
  • renally dose adjusted
  • BID wihtin 30 min of end of meal
16
Q

dose limiting tox of capecitabine

A
  • hyper ibli
  • diarrhea
  • hand-foot sydrome
  • mucositis

CI in DPD deficiency

DDI with warfarin and phenytoin (CYP2C9)

17
Q

oxaliplatin MOA

A
  • platinum analog, alkyalting agent (creates cross links in DNA)
  • not cell-cycle specific
18
Q

oxaliplatin ADR

A
  • peripheral neuroapthy (dose dependent)
    • dt accumulation of platinum in dorsal root gannglia
    • duloxetine may help
  • cold intolerancesensitivity (type of neuro tox)
    • happens right away
    • dt drug being metabolized to oxalate (chelates Ca) → Na voltage gates remain open - hyperexcitability
  • myelosupppresion
19
Q

Irinotecan MOA

A
  • topoisomerase-1 inhibitor
  • SN-38 is the active drug
20
Q

irinnotecan ADR

A
  • diarrhea
    • acute: dt cholinergic symptoms (diarrhea, watery eyes, flusshing, sweating) → give atropine in infusion center
    • chronic: general gut tox dt cytotixc action of drug → loperamide
  • fatigue
  • alopecia
  • myelosuppresion, neutropena
21
Q

Bevacizumab use in colorectal cancer

A
  • Given with chemo for synergistic effect (cuts off blood flow to tumor)
  • Used for metastatic colorectal cancer with infusional 5-FU based regimens as 1st or 2nd line

can alternatively use Ziv-aflibercept, but bevacizumab is preferred

22
Q

ramucirumab use in colorectal cancer

A

FDA approved for use in combo with FOLFIRI in pts who have progressed while being treated with 1st line bevacizumab, oxaplatin, and 5-FU/capecitabine regimen

  • Admin 60 min prior to FOLFIRI inf
  • Continue until disease progression or unacceptable tox
23
Q

EGFR inhibitors MOA

A
  • Inhibit epidermal growth factor receptor → skin ADR
  • pt must be KRAS wild type (no mutation)

If KRAS wt → qualify EGFR inhibitor
Cetuximab
Panitumumab

24
Q

EGFR use in colorectal cancer

A

used in metastatic colorectal cancer

colorectal gents
- cetuximab
- panitumumab

25
Q

regorafenib MOA

A
  • multikinase inhibitor: nhibit VEGFR 2 and 3, RET, KIT, PDGFR, and Raf kinase
26
Q

regorafenib use in colorectal cancer

A

FDA approved for later line treatment in metastatic colorectal cancer as monotherapy (salvage therapy)

27
Q

regorafenib DDI

A

CYP3A4

28
Q

regorafenib admi

A
  • PO QD with low fat meal 3W on, 1W off
  • Sotre in original container, 28D expiration date after opening
29
Q

regorafib ADR

A
  • hepatoox (BBW): check LFTs prior to starting
  • hemorrhage, delayed wound healing
  • cardiac issues
  • GI perforation
  • hand foot syndrome
  • diarrhea
  • mucositits
  • ifection
  • much much much more (try ot match adr to what the drug targets)

very hard for pts to tolerate, many adr

30
Q

HER2 therapy in colorectal cancers

A

Only indicated in HER2 amplifed tumors that are also RAS and BRAF wild type
- HER2 amplication rare in colorectal cancer
- recommenedd as subequent therapy options in pts who meet the above criteria

Agents
- trastuzumab + (pertuzumab or lapatinib): initial or subsequent
- fam-trastuzumab deruxtecan: subsequent

31
Q

Trifluridine + tipiracil (Lonsurf) use in colorectal cancer

A

metastatic colorectal cancer if pt has previously received 5-FU/capecitabie-, oxaplatin-, and irinotecan- based chemo, an anti-VEGF biotherapy
- Additionally, if pt KRAS wild type, they need to have tried anti-EGFR therapy
- this bitch very last line

32
Q

Trifluridine + tipiracil MOA

A
  • PO chemo
  • interefere iwth DNA syntehsis and inhibit cell proliferation by incorporation in DNA

  • trifluridine: thymidine based nucleoside analog (main cytotoxic agent)
  • tipiracil: thymidine phophorylase inhibitor → increases trifluridine exposure and has modest cytotoxic activity
33
Q

Trifluridine + tipiracil admin

A
  • PO BID on days 1-5 and 8-12 of a 28 day cycle
    • take within 1 hr of the end of breakfast and dinner
    • no need to dose adjust for hepatic or renal impairment
    • could potentially do a regimen of this + bevacizumab
34
Q

Trifluridine + tipiracil ADR

A
  • severe myelosuppression: monitor blood coutns prior to and on day 1 and 15 of each cycle
    • dose reduce and/or hold admin as clincally indicated
  • anemia
  • neutropenia
  • thrombocytopenia
  • fatigue
  • N/V/D
  • decreased appetite
  • abdominal pain
35
Q

immunotherapy use in colorectal cancer

A

only for MSI-H tumors (typically in stage 4)

agets:
- pembrolizumab
- nivolizumab

36
Q

BRAF inhibitor use in colorectal cacner

A
  • Only for BRAF genotyped tumor tissue (BRAF V600E mutation postiive) - aggressive tumor with poor prognosis
    **- Doublet therapy (Cetuximab + Encorafenib)
  • not first line (typically second or third)**
  • Resistance to BRAF inhibitors by feedback re-activaation of EGFR and downstream MEK and ERK pathways
37
Q

stage III colorectal cancer tratment

A
  • surgery + adjuvat chemo in most pts (5-Fu is our standard of care here - FOLFOX or CapeOx)
  • start chemo 4-8 weeks after surgery (can go up to 12 but not great), and do it for 6 months
    - If pt was low risk, could consider only 3 months (best evidence for 3 months is pts with low risk and on CapeOx)
38
Q

stage IV colorectal cancer treatment: resectable liver only or lung only metases

A

can consider sugery
- Give neoadjuvant first
- FOLFIRI, CapeOx, or FOLFOX +/- bevacizumab (remeber to dc bevacizumab 4 weeks prior
- FOLFIRI or FOLFOX +/- panitumumab or cetuximab if KRAS wildype
- Surgery, and then 2-3 months of chemo followed by staged resection of metastataic disease

39
Q

stage IV colorectal cancer treatment: unresectable liver only or lung only metases

or resecctable not doing surgery

A
  • chemo, targeted therapy, immunotherapy and evaluate disease Q2mo to determine resectability of live and/or lung mestases
  • Consider coloc resection if risk of obstruction or significant bleeding
40
Q

EGFR MAb ADR

A
  • infusion related reactions (pre-medicate before cetuximab admin)
  • hypoMg
  • paronchyia: infection of folds of tissue surrounding nails
  • acneiform rash

PHM 703: Crit Care/Heme/Onc (16 decks)

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