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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?.
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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)
(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 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