VP L2 Colorectal cancer Flashcards
Colorectal caner is the …. most common cancer in the UK
3rd
Colorectal cancer affects more men/woman?
What age?
Men
Over 60
Risk factors (3)
Famillial
dietary/lifestyle
other colorectal conditions
2 Familial risk factors
FAP (familial adenomatous polyposis)
and
HNPCC (hereditary non-polyposis colorectal cancer)
Dietary/lifestyle risks (6)
high intake of meat/animal fat Low fiber intake Regular consumption of aspirin/NSAIDS (REDUCES RISK) Inactive lifestyle Obesity
3 other colorectal conditions that predispose to CC
Ulcerative colitis
Previsous colorectual cancer
Crohn’s disease
Pathology of CC
polyp to benign adenoma to malignant tumour
vast majority are adenocarcenomas that arise from pre-existing polyps that develop in normal mucosa
How long does it take a polyp to become cancer
10 years
symptoms (6)
change in bowel habit abdo pain rectal bleeding/mucus weight loss anorexia
Anaemia (chronic bleeding from tumour site)
20% of resenting complaints are
acute large bowel obstruction (surgical emergency)
Differential diagnosis
IBS
and
Inflammatory bowel disease
4 diagnostic investigations
colonoscopy
felxible sigmoidoscopy
Ba enema
CT preop to check for metastases
How do we stage CC
Duke’s system traditionally
or
TNM more recent
How do we stage CC
Duke’s system traditionally
or
TNM more recent
what is first line treat for 80% of patients
Surgery
Segment of the large bowel resected
What percentage of patients suffer recurring disease
50%
When is radiotherapy indicated
rectal cancers only
and
post op to reduce incidence
aim of adjuvant chemo
post surgery to eradicate micrometastases
for what dukes score is chemo recommended
dukes C
NOT
A
What is the mainstay of chemo treatment for CC
5FU
How does 5FU work
converted intracellularly to metabolites that bind thymidylate synthase
thus
inhibiting synthesis of thymidine, DNA and RNA
What is given to increase the efficacy of 5FU
How does it work
folinic acid
prolongs inhibition of thymidylate synthase
side/effects of 5FU (6)
diarrhoea stomatisis nausea and vom bone marrow supression hand and foot syndrome excessive tear shedding
What adjuvant is given for DUKES C
oxaliplatin
5FU
folinic acid
How does oxaliplatin work
Cross links DNA, prevents replication and cell devision
Oxaliplatin s/e (4)
peripheral neruopathy
acute pharyngolaryngeal dysasthesia
bone marrow suppression
mild alopecia
What is a hickman line
central venous catheter coming out of your chest
Why Oxaliplatin de Gramont regime?
Infusion is important as tumour cells have low growth fraction
Also 5FU has t1/2=10mins and is s phase specific
What is the problem with de gramont regime?
increased incidence of hand and foot syndrome from 5FU
3 Issues with infusional devices
anxiety for patients
disposal of cytotoxic waste in patients homes
time consuming to fill for pharma
What is capecitabine
oral chemotherapy
how is capecitabine used
in combo with oxaliplatin in XELOX regime (instead of the de gramont component)
Advantages of oral capecitabine therapy
less invasive
no issues with sterility/short exp
reduces pharmacy cost and time
pt can administer medicines themselves
What is Capecitabine?
the prodrug of 5FU - three step acivation process, two steps occur preferentially in tumours
What is the capecitabine regieme
bd 14 days out or 21
de gramont regieme details
Chemo given every 2 weeks for 12 cycles as outpatient
Oxaliplatin 85mg/m2 over 2hrs IV infusion
Calcium folinate 350mg over 2hrs IV infusion
Fluorouracil 400mg/m2 IV stat
Fluorouracil 2400mg/m2 IV infusion over 46hrs in portable infusion device
Need Hickman (central) line or PICC line
de gramont regieme details
Chemo given every 2 weeks for 12 cycles as outpatient
Oxaliplatin 85mg/m2 over 2hrs IV infusion
Calcium folinate 350mg over 2hrs IV infusion
Fluorouracil 400mg/m2 IV stat
Fluorouracil 2400mg/m2 IV infusion over 46hrs in portable infusion device
Need Hickman (central) line or PICC line
How to treat metastatic disease
Surgery to relieve obstruction/symptoms
resection of liver metastases
5FU based regimes
plus other drugs (e.g. irinotecan)
What is irinotecan?
topoisomerase I inihibtor (enzyme invilved in unwinding of DNA during DNA repair)
Treatment summery: Duke’s A
Duke’s A: surgery only
Treatment summery: Duke’s B
Duke’s B: surgery + adjuvant chemotherapy in some cases (patients with risk factors such as vascular invasion of tumour, poorly differentiated tumour)
Treatment summery: Duke’s C
Duke’s C: surgery + adjuvant chemotherapy
Treatment summery: Duke’s C
Duke’s D (metastatic): surgery to relieve obstruction if needed, palliative chemotherapy +/- monoclonal antibodies to relieve symptoms & prolong survival
e.g. of a new mab therapy
Bevacizumab (avastin)
How does avastin work
VEGF inbitor - inhibits VEGF binding to receptor on tumour cell surface
VEGF usually stimulates angiogenisis
What is avastin licensed for?
Combination therapy with 5FU therapies
How is avastin given
IV infusion every 2/3 weeks
s/e avastin
GI perforation
haemorrhage
hypertension
arterial thromboembolism
What is cetuximab (erbitux)
mab that blocks EGFR
Cetuximab is licenced for
treatments of patients with EGFR expressing KRAS wild type
- in combo with chemo
or
-as a single agent in pt who have fails oxaliplatin and irinotecan based therapies
Cetuximab is now first line for
metastatic CC
in combo with oxaliplatin de gramont
Cetuximab is now first line for
metastatic CC
in combo with oxaliplatin de gramont
cetuximab s/e
rash
itching
infusion reactios (fever, chills, nausea, vomitting)
cetuximab s/e
rash
itching
infusion reactions (fever, chills, nausea, vomitting)
