Upper gastrointestinal cancers

Dr Sue DarbyConsultant Medical Oncologist

Weston Park HospitalSheffield

Introduction

• What’s UGI?

• Terminology

• Treatment intent

• Treatment options

• Clinical trials

What’s upper GI?

• 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

• Metastatic tumours (follicular breast, renal)

Treatment intentions

• Neoadjuvant

• (Downstaging)

• Adjuvant

• Curative

• Palliative

Treatment types

• 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

– 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 – 1st line

• 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 – 2nd line

• 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

• 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?