Upper gastrointestinal cancers
Dr Sue Darby
Consultant Medical Oncologist
Weston Park Hospital
Sheffield
Introduction
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What’s UGI?
Terminology
Treatment intent
Treatment options
Clinical trials
What’s upper GI?
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Oesophagus
GOJ
Stomach
(Small bowel)
What sorts of cancers?
• Mainly adenocarcinomas (lower
oesophagus downwards)
• Squamous cell carcinomas (usually upper
or mid oesophagus)
• Gastrointestinal stromal tumours (GIST)
• Lymphoma
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Metastatic tumours (follicular breast, renal)
Treatment intentions
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Neoadjuvant
(Downstaging)
Adjuvant
Curative
Palliative
Treatment types
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Chemotherapy
Radiotherapy
Chemoradiotherapy
Biological therapy
(Brachytherapy)
(Surgery)
Curative treatments
(Neo)adjuvant chemotherapy
• SqCC
– 2 cycles neoadjuvant chemotherapy
– 2 drugs – cisplatin and 5 fluorouracil
– OEO2 trial – increases 2 year survival from
35% to 45% (surgery vs chemo+surgery)
– Surgery 4-6 weeks after chemo
(Neo)adjuvant chemotherapy
• AdenoCa
– 3 cycles neoadjuvant and 3 cycles adjuvant
chemotherapy
– 3 drugs – epirubicin, cisplatin and
capecitabine
– MAGIC trial – increases 5 year survival from
23% to 36.5% (surgery vs chemo+surgery)
– Surgery 4-6 weeks after neoadjuvant
chemotherapy
ST03
• ECX +/- biological therapy
• HER2 positive
– +/- lapatinib
– potentially operable lower oesophageal, GOJ
and gastric adenoca
• HER2 negative
– +/- bevacizumab
– gastric adenoca only
Side effects
• Benefits outweigh risks (in majority)
• GI – nausea, vomiting, diarrhoea, constipation,
mucositis
• Skin – hair loss, hand-foot syndrome
• Neurotoxicity – peripheral, tinnitus/deafness
• Renal toxicity
• Fatigue
• Haematological – thrombocytopenia, anaemia,
neutropenia (neutropenic sepsis)
• Cardiovascular – angina/MI, arrhythmias
Contraindications/Cautions
• Ischaemic heart disease
• Renal disease
• Perfomance status
• Patient choice
Chemoradiotherapy
• SCOPE trial – 2 yr survival >50%
• 2 cycles of neoadjuvant cisplatin and capecitabine
• 5 weeks of daily radiotherapy concomitantly with a
further 2 cycles of capecitabine
• Side effects
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odynophagia
fatigue
severe dysphagia (towards end of radiotherapy)
treatment related stricture (late effect) - may require dilatation or
stenting
• Advantages over surgery – can treat some surgically
untreatable cancers (eg locally invasive)
• Disadvantages – nodal disease/field size
Palliative treatments
Palliative chemotherapy –
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• SqCC
– Cisplatin/5FU
• AdenoCa
– Oesophagus - EOX – epirubicin, oxaliplatin,
capecitabine – adds few months on average
– Gastric/GOJ
• HER2 negative – EOX
• HER2 positive – cisplatin, 5FU, trastuzumab
(Herceptin) + maintenance trastuzumab
• TOGA trial
REAL2
• ECX/ECF/EOX/EOF
• No significant difference in survival
between arms
• Around 9-11 months median survival
• Trend towards best with EOX
• Delivery issues
• Led to change in practice from using ECF
(PICC lines, continuous infusional chemo)
to EOX (oral 5FU, no PICC)
Palliative chemotherapy –
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• SqCC – nothing
• AdenoCa – docetaxel
– COUGAR trial – adds 2 months on average
• Symptomatic benefit/BSC
• Early phase trials (Leeds)
Palliative radiotherapy
• Symptomatic benefit
• If local disease only can offer some local control
• Good for:
– Dysphagia
– Bleeding
– Tumour pain
• Side effects minimal and short-lived –
odynophagia, increased dysphagia, fatigue
Clinical trials
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Only way to improve outcomes
What current treatments are based on
Form basis for future (better) treatments
Importance of introducing idea to patients
at early stage
• Early referral of patients
• Opportunity
– patients
– doctors
Questions?