Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma.
About 40% of nonfunctioning pancreatic endocrine carcinomas (NF-PEC) cannot be cured by surgery due to advanced stage disease. Somatostatin analogues have been proposed as first line therapy in these cases. We performed a prospective phase IV study to assess the efficacy of octreotide in advanced NF-PEC and identify factors predictive of response to therapy. Twenty-one consecutive patients with octreoscan-positive advanced-stage well-differentiated NF-PEC were treated with long-acting release octreotide 20 mg i.m. at diagnosis. The immunohistochemical expression of somatostatin receptor 2 (SSTR2) and the quantitative mRNA analysis of SSTR2 and SSTR5 were assessed in 12 tumours. The tumour proliferative fraction was assessed by immunohistochemistry for Ki-67. Eight patients (38%) had stable disease (SD) after a median follow-up of 49.5 months. Thirteen patients (62%) developed progression after a median of 18 months. Tumour progression correlated with a proliferative index>or=5% (P=0.016), weight loss (P=0.006) and absence of abdominal pain (P=0.003) at diagnosis. Other clinical (age, gender and primary tumour resection) or pathological parameters (site, size and liver metastasis) lacked significant correlation with tumour progression. No difference in the amount of SSTR2 mRNA and protein or SSTR5 mRNA was found between tumours that were stable (n=5) and seven tumours that progressed (n=7). Treatment with long-acting release octreotide was associated with stabilization of disease and a good quality of life in 38% of patients. A Ki-67 index>or=5% and/or the presence of weight loss may justify more aggressive therapy without waiting for radiologically proven progression of disease.
Butturini
G
G
Department of Surgical and Gastroenterological Sciences, University of Verona, Chirurgia B, Policlinico GB Rossi, Piazzale LA Scuro, 37134 Verona, Italy.
Bettini
R
R
Missiaglia
E
E
Mantovani
W
W
Dalai
I
I
Capelli
P
P
Ferdeghini
M
M
Pederzoli
P
P
Scarpa
A
A
Falconi
M
M
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018273:Carcinoma, Islet Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D015282:Octreotide