Upper gastrointestinal cancers Dr Sue Darby Consultant Medical Oncologist Weston Park Hospital Sheffield

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)

Curing patients Neoadjuvant and adjuvant chemotherapy Aim – to eradicate micrometastatic disease before (neoadjuvant) or after (adjuvant) surgery Chemoradiotherapy – concurrent As effective as surgery (!) in SqCC Has advantages and disadvantages Can be used in some locally advanced (inoperable) tumours Cannot cover all nodal areas (radiotherapy field)

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 HER2 negative +/- 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)

REAL3 EOX +/- panitumumab NO benefit of adding panitumumab to standard chemo

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?