1. Oesophageal Cancer
Asma, Bhumi, Faith, Gold, Kunal and Rebecca
Group D1 and H1
UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE

2. Poster Title
Names of Authors
Addresses
UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE
Oesophageal cancer is a cancer of the oesophagus which carries ingested food to the stomach. 13th most common cancer in the UK.
Main risk factors are Smoking and consumption of Alcohol
There are two main types of oesophageal cancer:
Prevalence
1 Year Prevalence 5 Year Prevalence 10 Year Prevalence
Male
2,864 5,727 6,978
Female 1,418 2,868 3,674
Persons 4,282 8,595 10,652
Squamous Cell Carcinoma (SCC)
Present in the upper region of the oesophagus
Occurs due to rapid, uncontrolled proliferation of
squamous cells lining the upper region of the
oesophagus.
Incidence
Symptoms
Persistent Indigestion Difficulty Swallowing
Bleeding into the
oesophagus
Hoarseness, or
persistent cough
Chest pain Weight loss
Adenocarcinoma
Present in the lower region of the oesophagus.
Occurs when glandular cells which secrete mucus
into the oesophagus proliferate rapidly and
uncontrollably.
[2]Cancer Research UK Pie Chart stating
statistics about oesophageal cancer
[1] Cancer Research UK - Incidence of Oesophageal cancer in
males and females between different age ranges
[3] Graph from Medscape showing incidence of
Adenocarcinoma and SCC
[4] Figures released by Cancer Research UK of people still alive at the end of 2006
Introduction

3. Poster Title
Names of Authors
Addresses
UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE
Staging
There are 2 main ways of staging oesophageal cancer known as the:
TNM System
• Stage T (subdivided into T1-T4b) stands for
‘Tumour’ and it describes its’ progression.
• Same principle applies for Stage N (subdivided into
NO-N3) which stands for ‘Nodes’.
• Stage M (subdivided into MO-M1) stands for
“Metastasis”. It refers to whether the cancer has
spread to another part of the body or not.
Number System
Stage TNM Equivalent Description
T N M
0 - Abnormal cells present in
oesophagus lining
1A 1 0 0 Cancer only in oesophagus lining
1B 2 0 0 Cancer spreads into muscle layer
2A 3 0 0 Cancer spreads through oesophagus
wall
2B 1 1 0 Cancer spreads into top 2 layers of
oesophagus
3A 1/2 2 0 Same as 2B as well as spreading to
3-6 lymph nodes
3B 3 2 0 Cancer spreads to outer layer of
oesophagus and 3-6 nodes
3C 4b Any 0 Cancer spreads to nearby structures
(e.g. spine) and nodes
4 Any Any 1 Cancer spreads to nearby nodes and
other parts of the body (e.g. liver)
[5] T and N stages of oesophageal cancer
[6]Visual representation of different stages of oesophageal cancer
using the number system

4. Poster Title
Names of Authors
An anthracycline that intercalates
into DNA and inhibits
topoisomerase II.
[7]– Epirubicin mechanism of
action
[8]– Epirubicin free radical production
Cisplatin works by binding to DNA and non-
DNA targets which subsequently, induces cell
death through necrosis, apoptosis or both.
A pyrimidine analogue antimetabolite that
inhibits the action of the enzyme thymidylate
synthase.
[11]- 5-fluorouracil mechanism of action
ECF Drug Mechanisms
CisplatinEpirubicin 5-Fluorouracil (5-FU)
ECF Combination therapy
Why combination therapy?
• Combining drugs that act in
different phases of the cell cycle
increases the number of cells
exposed to cytotoxic effects,
leading to a more complete kill
• To reduce resistance
ECF effect on cell cycle
5-FU
Epirubicin
Cisplatin is non cell cycle specific
[12]
Regimen Details
Drug Dose Administration Duration
Epirubicin 50mg/m2 IV D1
Cisplatin 60mg/m2 IV D1
5-FU 200mg/m2/24hrs IV Continous infusion D1-21
You have ECF in 3 week cycles. You may have 6
to 8 cycles lasting up to 6 months in total.
[13]
[10] -DNA distortions
caused by cisplatin binding
[9] - Mechanism of cisplatin
induced cell death

5. Administration
• Epirubicin as an
injection directly into
central line or cannula
with a drip (infusion) of
fluids to flush it through
• Cisplatin, in 1 litre
Sodium Chloride 0.9% IV
over 2 hours 1litre
Sodium Chloride 0.9% +
40mmol KCl + 1g
MgSO4 IV infusion over
2 hours
• Then 500ml Sodium
Chloride 0.9% IV
infusion over 60 minutes
• 5-FU infusion, via central
venous catheter and
ambulatory infusion
device [14]
0% 5% 10%15%20%25%30%35%
Complete disappearance of the
oseophageal tumour
Partial response
No improvement
Treatment Outcome, determined
endoscopically
Study
Conclusion:
“This regimen appeared particularly
useful in inducing response in the
primary tumour and in liver and lymph
node metastases. This brief period of
response may allow a window for re-
assessment with view to surgery” [15]
Side Effects and Dose-limiting toxicity
Delayed Late
 Alopecia
 Cardiotoxicity (Dose limiting)
 Ototoxicity
 Amenorrhoea
 Skin changes e.g rashes and flare
 Loss of fertility
 Nephrotoxicity
Immediate
 Acute Emesis
 Allergy
 Burning sensation at site (due to
extravasation)
 Urine Discoloration
 Delayed Emesis
 Fatigue
 Diarrhoea (Dose limiting)
 Myelosupression (Dose limiting)
 Reduced appetite
 Metallic taste
 Peripheral neuropathy
 Numbness/Tingling of fingers
 Mucositosis
[17]- Supportive therapy regimes to be given when side-effects or toxicity do occur.
• Study showing that oeseopahageal cancer can be
downgraded using ECF, allowing possibility of surgery,
carried out at the Royal Marsden Hospital
• The patients in this study had irresectable, locally
advanced or metastatic squamous oesophageal carcinomas
• After ECF treatment, 5 patients were able to undergo
treatment [16]Graph
showing people’s
response to ECF
treatment

6. Addresses
Supportive therapy
Resistance
• ABC Efflux transporters increased
• Decreased topoisomerase II inhibition
• Increases levels of glutathione or
glutathione peroxidase activity
• Overcome resistance by treatment with
verapamil and BSO
Epirubicin
• Increased thymidylate synthase
• Decreased affinity of enzyme for active drug
• Reduced availability due to reduced folate
cofactor (FH4)
• Increased drug inactivation
• Decreased conversion to active form
• Altered amount of target enzyme or receptor
• LEUCOVORIN to overcome resistance
5-Fluorouracil
• Up regulation of metabolizing
enzymes
• Increased capacity to repair intrastrand
adducts
• Methallothionein induction
• P-glycoprotein (Efflux transporter)
• Thymidylate synthase
• Cellular thiols
• Glutathione S transferase
• Mellathionein
• Inhibiting the above to overcome MDR
• Less likely because combination therapy used
Multidrug Resistance MDR (Biomarkers)
Cisplatin
[18]-Diagram showing different resistance mechanisms
The goal of
supportive care is
to prevent,
control, or relieve
complications
and adverse
effects associated
with the
treatment
Cardiac
monitoring,
Dexrazoxane
Blood
transfusion
Antiemetics –
5-HT3 receptor
antagonist,
dexamethasone,
NK -1 receptor
antagonist
Antimicrobial
prophylaxis,
G-CSF
Laxatives
and
Antimotilit
y drugs
Nephrotoxicity:
Hydration with
saline +
administration
of Mannitol Analgesics and
anaesthetics e.g.
xylocaine
and saline
mouthwash

7. Poster Title
Names of Authors
Addresses
UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE
Conclusion
References
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[3] Medscape (2014). http://www.medscape.com/viewarticle/557839 . Last accessed 23rd November 2014.
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[11] Schwarzenbach H. (2010). Predictive diagnostics in colorectal cancer: impact of genetic polymorphisms on individual outcomes and treatment with fluoropyrimidine-based chemotherapy. Available:
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therapeutic-approaches
[19] Cunningham D, Allum W, Stenning S, et al. Perioperative Chemotherapy Versus Surgery Alone for Resectable Gastroesohpageal Cancer. New England Journal of Medicine. 2006 ; 355:11-20.
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ECF Therapy is recommended for treatment of Adenocarcinomas, especially prior to or following surgery.
European Trial on ECF therapy concludes:
• Both progression-free survival and overall survival were significantly improved with the use of ECF.
• Rates of complications during surgery were nearly identical: 46% for those treated with ECF and 45% for the group who underwent
surgery only.
• At 5 years, overall survival was 36% for those treated with ECF compared with only 23% for those treated with surgery only.
• Progression-free survival was reduced by 34% among patients treated with chemotherapy compared to those treated with surgery only.
• Treatment with ECF was generally well tolerated. [19]