Whats new in treatment of Neuroendocrinecarcinoid tumours

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Whats new in treatment of Neuroendocrine/carcinoi
d tumours

• Dr John Ramage
• Consultant physician and senior lecturer.
• North Hampshire Hospital and Kings College
  Hospital

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Carcinoid/NET terminology
Pancreatic endocrine tumours
Breast/ SC lung cancer
Neuroendocrine tumours
Carcinoid
Carcinoma with neuroendocrine differentiation
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Multi-specialty disease?

• Belongs to
• Endocrinologists
• Gastroenterologists
• Hepatologists/hepatic surgeons
• Oncologists
• Radiologists
• Nuclear medicine physicians

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Neuroendocrine tumours-therapy

• Octreotide
• Interferon
• Embolisation
• Chemo-embolisation
• Chemotherapy
• Liver resection
• Radio Frequency Ablation
• Radionuclide therapy
• Liver Transplantation

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Radionuclide therapy

• Of use in those with positive radionuclide scans
• Targets tumour and metastases1,2
• 131I-labelled MIBG
• 111In-octreotide
• 90Y-octreotide/DOTATOC
• 177Lu-DOTA Tyr3-octreotate
• 90Y-lanreotide
• Symptomatic and antiproliferative effects

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Indium111

Octreotide
Tumour cell

Cell destroyed
Radioactivity
Not much effect in low dose. Too toxic in high
dose
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Yttrium90

Octreotide
Tumour cell

Cell destroyed
Radioactivity
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Lutetium177

Octreotide
Tumour cell

Cell destroyed
Radioactivity
2 patients treated in UK
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Iodine131

MIBG
Tumour cell

Cell destroyed
Radioactivity
ONLY CURRENT LICENSED NUCLEAR THERAPY
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Radionuclides When to treat maximum dose

• Early? Late?

Course of disease--------- x years
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Nuclear therapy-Side effects

• Bone marrow suppression
• Anaemia, bleeding, infections
• Kidney failure
• Effects of radiation exposure
• Isolation

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Neuroendocrine tumours-therapy

• Octreotide
• Interferon
• Embolisation
• Chemo-embolisation
• Chemotherapy
• Liver resection
• Radio Frequency Ablation
• Radiometabolic therapy
• Liver Transplantation

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Chemotherapy
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Chemotherapy- new drugs

• Temozolamide (oral)
• Attacks dividing cells.
• More useful in progessing pancreatic NET
• New combinations
• NET01 study combination chemotherapy for
  pancreatic NET.

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Chemotherapy- side effects

• Bone marrow suppression
• Anaemia, infection, bleeding
• Nausea/ fatigue
• Reduced appetite/ loss of weight
• Problems with intravenous drip sites
• And many more..

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New drugs- antibodiesabs and ibs

• Growth factor inhibitors
• VEGF inhibitors
• Bevacizumab (Avastin- Roche). Phase 2 trials in
  progress. 10-15 response. iv
• Sorafenib 9 response . oral
• Sunitinib- trials ongoing. oral
• mTOR growth factor inhibitor
• RAD001 (Novartis). Oral.

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Growth factor inhibitors
Inhibitor
TUMOUR CELL
Growth factor
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RADIANT study

• RAD 001 is a drug that inhibits mTOR
• mTOR is a growth factor for some NETs
• Phase 2 studies- 20 partial response
• Trial starting soon- progressive disease only.

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-Abs and -ibsSide effects

• Mouth/ throat ulcers
• Bone marrow suppression minor
• Skin rashes
• Allergic reactions
• In general less than chemotherapy

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SIRT in Carcinoid liver lesions
Pre-yttrium-90 microspheres
3 mo. Post Treatment
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CT portal phase- secreting carcinoid
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Prognostic factors
Risk factors
Liver metastases- therapy
Site of primary- Mid/foregut
Age/ length of time with disease
Fitness for surgery/ RFA
Presence of carcinoid heart disease
Appearances of Biopsy (Histology)
Extent of disease/ resectability/ remaining
liver function
Decision on type of therapy
Hormone secretion type and levels
Patient factors
Utility to the patient/ preferences
QoL- existing and expected
Disease outside liver? (Primary or secondary)
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There are often too many choices
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Possible options for liver NET
Liver transplant
Liver metastases
Liver surgery
New drugs/ RAD001
RFA
Chemotherapy/ STZ5FU
Radionuclide/ MIBG or Yttrium
(Chemo) embolisation/ SIRT
Octreotide/Interferon
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Risk factors
Prognostic factors
Liver metastases- therapy
Site of primary- Mid/foregut
Age/ length of time with disease
Fitness for surgery/ RFA
Presence of carcinoid heart disease
Histology/ proliferative index (Ki67)
Extent of disease/ resectability/ remaining
liver function
Decision on type of therapy
Hormone secretion type and levels
Patient factors
Utility to the patient/ preferences
Extrahepatic disease? (Primary or secondary)
QoL- existing and expected
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Decision Tree
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ExampleSurgical treatment for primary tumour

• Primary sites
• Appendix
• Small bowel ( duodenum or ileum)
• Pancreas
• Lung
• Large bowel (colon)

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Surgery- remove segment of bowel/pancreas if
possible and if no other spread
??surgery to bowel if already spread to liver-
debatable
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RESECTION OF PRIMARY
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Source for probabilistic and outcome data
Peer group views
Analysis of UK data- 350 patients with
liver metastases
Published evidence (All evidence now searched)
Patient details and preferences
Rational choice
Decision aid
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Conclusions

• There are a lot of treatments
• Many are unproven in scientific trials
• Many are very expensive
• Many have serious side effects
• Unclear when to use a treatment
• We need clearer ways to decide which treatment is
  best and when to give it!

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Acknowledgements

• The team at Basingstoke
• Dr Adil Ahmed, research fellow
• Barbara King
• Mr Rees, Ms Welsh, Dr Graham Plant
• The team at Kings
• Dr Simon Aylwin
• Nikie Jervis/ Sally Thomas
• Dr Suzanne Ryan, Professor Heaton, Mr Rela