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

3. Introduction What’s UGI? Terminology Treatment intent
Treatment options
Clinical trials

4. What’s upper GI?
Oesophagus
GOJ
Stomach
(Small bowel)

5. 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)

6. Treatment intentions Neoadjuvant (Downstaging) Adjuvant Curative
Palliative

7. Treatment types Chemotherapy Radiotherapy Chemoradiotherapy
Biological therapy
(Brachytherapy)
(Surgery)

8. 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)

9. Curative treatments

10. (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

11. (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

12. ST03 ECX +/- biological therapy HER2 positive HER2 negative
+/- lapatinib
potentially operable lower oesophageal, GOJ and gastric adenoca
HER2 negative
+/- bevacizumab
gastric adenoca only

13. 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

14. Contraindications/Cautions
Ischaemic heart disease
Renal disease
Perfomance status
Patient choice

15. 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

16. Palliative treatments

17. 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

18. 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)

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

20. Palliative chemotherapy – 2nd line
SqCC – nothing
AdenoCa – docetaxel
COUGAR trial – adds 2 months on average
Symptomatic benefit/BSC
Early phase trials (Leeds)

21. 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

22. 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

23. Questions?