Predictive factors of antiproliferative activity of octreotide LAR as first-line therapy for advanced neuroendocrine tumours.
BACKGROUND
The antiproliferative activity of octreotide LAR in neuroendocrine tumours (NETs) has been demonstrated by small retrospective studies and confirmed by a prospective phase III trial (PROMID). However, there are limited data about the duration and predictors of response. The aim of our retrospective study was to determine the time to radiological progression (TTRP) of disease and the factors that were associated with better response.


METHODS
A total of 254 treatment naïve patients with advanced NETs and positive somatostatin receptor scintigraphy were included. Mean follow-up period was 42 months.


RESULTS
The location of primary was in the small bowel in 204, pancreas in 22, lungs in 14, rectum in 7 and unknown in 7 patients. Most tumours were well-differentiated, G1 (58%) and G2 (23%). The majority of patients commenced octreotide LAR due to functional symptoms (57%), radiological progression (10%) or in the presence of asymptomatic and stable disease on the basis of data from the PROMID trial (18.5%). Partial response occurred in 5%. For all patients, the median TTRP was 37 months (95% confidence interval, CI: 32-52 months). There was a statistically significant shorter TTRP in patients with pancreatic tumours, liver metastases and intermediate grade tumours. Extremely raised (>10 times the upper limit of normal) baseline chromogranin A levels were associated with an unfavourable outcome. In contrast, male sex, carcinoid heart disease and initiation of treatment in the presence of stable disease were predictive of a better response. Age, extra-hepatic metastases, presence of mesenteric desmoplasia, previous resection and functional status of the primary tumour did not affect response.


CONCLUSIONS
The duration of the antiproliferative effect of octreotide LAR seems to be longer than previously reported. This study has identified several predictors of response in a large cohort of patients with NETs on somatostatin analogue therapy.
Centre for Gastroenterology, Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Faidon-Marios
FM
Laskaratos
Department of Infectious Disease Epidemiology, School of Public Health, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
Martin
M
Walker
Centre for Gastroenterology, Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Keval
K
Naik
Centre for Gastroenterology, Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Emmanouil
E
Maragkoudakis
Centre for Gastroenterology, Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Nikolaos
N
Oikonomopoulos
Department of Radiology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Lee
L
Grant
Centre for Gastroenterology, Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.|UCL Cancer Institute, University College London, London WC1E 6DD, UK.
Tim
T
Meyer
Centre for Gastroenterology, Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Martyn
M
Caplin
Centre for Gastroenterology, Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK.
Christos
C
Toumpanakis
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis
D018931:Antineoplastic Agents, Hormonal; D015282:Octreotide