Colorectal Cancer Flashcards

1
Q

Epidemiology

  • ___ leading cancer in incidence and death in men and women
  • incidence is increased in industrialized nations with males having a slightly increased incidence
  • 5-year survival is ~ 91% in early disease
A
  • 3rd
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2
Q

Risk Factors

Age
- increases starting after age of __ and is greater after 50 years of age

Family history of colon cancer

Hereditary syndromes
- Familial Adenomatous Polyposis (FAP)
- Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Dietary Factors:
* High fat, Low ___ , Reduced folate, Reduced calcium

Polyps: A small % of these will develop
into cancer

lifestyle

Ulcerative coitis/Crohn’s disease
- Chronic ___ may be predisposing factor

A
  • 40
  • fiber
  • inflammation
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3
Q

Pathophysiology

Malignant polyps tend to grow from the
inner basement membrane of the ___outward into the mucosa,
submucosa, muscularis, and serosa

Metastatic spread
- Via lymphatic and hematogenous routes to the lymph nodes, lungs, liver, and bone

> 95% of colorectal cancers are
___

A

bowel wall $
adenocarcinomas

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4
Q

Presentation

  • May be asymptomatic
  • Often presents with rectal ___ ,
    possibly associated with anemia
  • Change in bowel habits
  • Nausea/vomiting
  • 20 – 25% will present with ___
    disease
    – Jaundice, hepatomegaly, weight ___
A

bleeding
metastatic
loss

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5
Q

TNM Staging - Definition of T

A

basically how deep it goes

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6
Q

Additional Testing-Work Up

___ DNA ___ repair (dMMR)
- 19% of colorectal cancer

Test for microsatellite instability (MSI) or loss of genes involved in DNA MMR
* MSS = Microsatellite stable tumor
* MSI-L = Low level microsatellite instability
* MSI-H = High level microsatellite instability
* pMMR = Proficient mismatch repair
* dMMR = Defective mismatch repair

A
  • Defective, mismatch
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7
Q

Early-Stage Disease and MMR

  • dMMR or MSI-H tumor predicts a
    decreased benefit from adjuvant 5-FU based therapy for stage __ disease
  • Stage ___ patients with dMMR or MSI-H disease **can benefit **from adjuvant 5-FU
A
  • II
  • III
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8
Q

T or F: All patients with a colon cancer diagnosis should be tested for mismatch repair or microsatellite instability

A

T

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9
Q

Treatment Goals

Stage I, II, III
– Considered potentially ___
– Intent of eradicating known and
micrometastatic tumor sites
– Achieve ___ and avoid disease recurrence

Stage IV
– Incurable/ ___
– Decrease symptoms, avoid disease-related complications

A
  • curable
  • remission
  • palliation
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10
Q

Localized Therapy (Stage I and II)

___ alone is definitive therapy
- Partial or total colectomy + lymph nodes

No proven benefit with chemotherapy in stage ___ disease

  • Patients receiving chemotherapy with no adverse prognostic features showed no difference in survival
  • Can recommend adjuvant chemotherapy in Stage II disease if the patients are considered ___ risk
  • Remember MSI and/or MMR status: If ___ or ___ , then will not benefit from chemotherapy
    for stage II disease
A

Surgery
II
high risk
dMMR, MSI-H

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11
Q

Stage II Disease (Chemotherapy)

  • ___ is reasonable for high risk or
    intermediate risk stage II patients and is not indicated for good or average risk stage II patients
  • ___ can also be an option
A
  • FOLFOX
  • CapeOX
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12
Q

FOLFOX

A

5-Fluorouracil, leucovorin, and oxaliplatib

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13
Q

CapeOX

A

Capecitabine, oxaliplatin

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14
Q

FOLFIRI

A
  • irinotecan
  • leucovorin
  • fluorouracil
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15
Q

Stage III Disease

  • Surgery including regional lymph node
    removal + Chemotherapy are indicated for this stage of disease
  • ___ appears to be = to bolus
    5-FU/leucovorin in Stage III patients
A

Capecitabine

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16
Q

Stage II Chemo

  • mFOLFOX6
  • CapeOX
A
17
Q

IDEA Conclusions

With CapeOx : 3 months as effective as 6 months
- Especially in low-risk patients

With FOLFOX : 6 months was ___ effective than 3
months
- Especially in high-risk patients

Results suggest risk-based approach to determiningduration of adjuvant therapy

A
  • more
18
Q

Regimen Considerations

FOLFOX
* Requires ___
* 2-day pump
* More infusions overall
* increased myelosuppression
and ___ sores

A

pump
mouth

19
Q

Regimen Considerations

Port not required
* ___ infusions overall
* increased ___ syndrome and ___

Capecitabine
– ___ dose adjustments
– Adherence
– Copay
– Drug/drug interactions

A
  • less
  • hand-foot, diarrhea
  • renal
20
Q

Metastatic Disease

~ 50-60% of patients diagnosed with colon cancer will develop metastatic disease
- Chemotherapy is mainstay of therapy
- Survival has increased from 12 months with 5-FU monotherapy to ~ 2 years with the addition of
___ , ___ , and newer biologics

Surgery can play a role in isolated
disease
- Could achieve OS benefits of 20-50%

Radiation therapy
- Role for ___ of symptoms

A
  • irinotecan, oxaliplatin
  • palliation
21
Q

Which Chemo Regimen To Use?

Other co-morbidities that may determine therapy:
- ___
– ___ deficiency
– 1 versus 2 versus 3 drugs

A

Neuropathy
UGT1A1

22
Q

Advanced Disease and MMR

Predict benefit to PD-L1 inhibitors
- ___ and ___ shown benefit in metastatic setting
- Both drugs are approved for patients
unresectable or metastatic, with dMMR or MSI-H tumors ___ FOLFOX and FOLFIRI
- As stated previously, all patients should be tested for dMMR/MSI status regardless of stage

A
  • Pembrolizumab, nivolumab
  • after
23
Q

Predictive Biomarkers

K-RAS
- Mutations predict lack of response to ___ monoclonal antibodies
- Do not use Cetuximab and panitumumab
- Recommend testing in all metastatic disease

BRAF
- 5-15% of patient will have this mutation
- Test all patients in metastatic setting

A
  • anti-EGFR
24
Q

metastatic chemo options (6)

A
  • mFOLFOX6
  • CapeOX
  • FOLFIRI
  • bevacizumab
  • cetuximab
  • FOLFIRINOX
25
Q

1st Line Metastatic Disease

Accepted chemotherapy regimens if
someone can not tolerate intensive
chemotherapy include:

A
26
Q

Second Line Therapy

Disease progression with prior oxaliplatin based regimens

A
27
Q

Second Line Therapy

Disease progression with prior irinotecan-based regimens

A
28
Q

Third Line Therapy

A
29
Q

Colon Cancer Screening Tests

  1. Primarily detect cancer
    Fecal occult blood test ( ___ )
    - High false- ___ rate

Fecal immunohistochemical test (FIT), or FIT DNA
- Detects ___

OR

  1. Detect cancer and advanced lesions
    - Endoscopic and radiologic exams
    - colonoscopy

Screening guidelines applies to men and women > __ years old

A
  • FOBT
  • negative
  • hemoglobin
  • 45
30
Q

Colon Cancer Prevention

Diet
- ___ fiber, ___ fat
- ___ -rich diet: ↓’s proliferative response to fatty acids and bile acid

NSAIDs, ASA
Colectomy

A
  • high, low
  • calcium
31
Q

5-FU

  • FUTP incorporates into RNA and impairs protein synthesis
    – FdUMP binds thymidylate synthase (TS) and reduces rate of DNA synthesis, replication, and repair
  • Extensively metabolized by dihydropyrimidine dehydrogenase (DPD) in the liver
  • Patients with DPD deficiency have exaggerated toxicities
  • ___ stabilizes the binding of FdUMP to TS resulting in enhancement of the toxicity of FdUMP
A
  • Leucovorin
32
Q

Common Agents: Irinotecan

Irinotecan
- Inhibits topoisomerase __
- Dose-limiting toxicities are ___ and ___
- Early onset diarrhea – Can be while the patient is getting the drug - Cholinergic syndrome: treated with ___
- Late-onset diarrhea –Starts more than 24 hours after irinotecan administration
– May last 3-5 days and can be fatal (use high dose lopiramide)

A
  • I
  • neutropenia, diarrhea
  • atropine
33
Q

Oxaliplatin and Capecitabine

Oxaliplatin - 3rd generation platinum compound
- Cross-links DNA, inhibiting DNA replication
* Inactive as a single agent
* Given with 5-fluorouracil and leucovorin to make FOLFOX
* Unique toxicities: ___ , ___ intolerances, sensation of not being able to breathe

Capecitabine
- Three-step activation process
- Oral prodrug of ___
- Dose-limiting toxicity is ___ syndrome and diarrhea

A
  • neuropathy
  • cold
  • 5-FU
  • hand-foot
34
Q

Cetuximab

Monoclonal antibody (human/mouse
chimeric)
- Binds to the extracellular domain of ___
- Used only in ___ wild type patients

Adverse events
* infusional reaction - Rapid onset of airway obstruction (bronchospasm, stridor, hoarseness) urticaria, or
hypotension; usually occurs with first infusion
* Acneform ___, asthenia/malaise, fever, nausea
* Hypo ___
– Premedicate with an ___ antagonist is recommended

Panitumumab has same AEs

A
  • EGFR
  • KRAS
  • rash
  • hypomagnesemia
  • H1
35
Q

Bevacizumab

Monoclonal antibody (recombinant humanized) which binds to ___ potentially decreasing angiogenesis
- Given in combination with 5-FU, leucovorin and irinotecan
- Significant toxicity: Bleeding, hypertension, proteinuria, thromoboembolism, gastrointestinal perforations, decreased wound healing
- many black box warnings

A

VEGF

36
Q

Regorafenib

Multi-kinase inhibitor targeting angiogenesis ( ___ 1-3, KIT, PDGFR-alpha, PDGFR-beta, BRAF,
BRAFV600E, and others
- Can use in patients with ___ mutations
- Toxicities: Hypertension, mucositis, fatigue, hand
foot syndrome, hemorrhage, rash, metabolic disorders, diarrhea, myelosuppression, increased liver
function tests, proteinuria
- (Rare): Squamous cell carcinoma of the skin
- High fat meals increase drug concentrations
- Drug interactions to worry about: CYP3A4

A

VEGF
KRAS

37
Q

TAS-102 (Trifluridine / Tipiracil)

Used after patients fail: 5-FU, oxaliplatin- and irinotecan-based chemo, an anti-VEGF therapy,
and if RAS wild-type, an anti-EGFR therapy
- pretty much after they faily everything

Adverse reactions:
–Fatigue, nausea/vomiting, decreased appetite, diarrhea, abdominal pain, anemia, neutropenia, thrombocytopenia, weakness
In general, better tolerated than ___

A

regorafenib