Feasibility and efficacy of combined cisplatin plus irinotecan chemotherapy for gastroenteropancreatic neuroendocrine carcinomas

Abstract

No standard treatment is currently available for gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC). Therefore, we conducted this study to evaluate the effect of the combination of irinotecan and cisplatin in the treatment of GEP-NECs. Clinical data of 16 locally advanced or metastatic GEP-NEC patients treated with irinotecan plus cisplatin regimen in our center from September 2009 to August 2011 were reviewed. The regimen included 2-week cycles of 180 mg/m(2) irinotecan and 50 mg/m(2) cisplatin on day 1. Median age was 57 years. The overall response rate was 57.1%, with a disease control rate of 78.6%. One patient achieved pathologic complete response and underwent esophagectomy after chemotherapy. Two patients who had gotten progressive disease were given sequential octreotide long-acting release (LAR) treatment and got disease progression again within 1 month. Six patients who achieved disease control received octreotide LAR as maintenance treatment. The total number of cycles of octreotide was 41, with a median of 4.5 (3-20 cycles). The progression-free survival was 5.5 months, with overall survival of 10.6 months. Grades 3-4 hematological adverse events (AEs) occurred in 10 patients (62.5%) and 3 patients (18.7%) suffered grades 3-4 non-hematological AEs; no patient died of AEs. The irinotecan plus cisplatin chemotherapy is moderately effective and tolerable well tolerated in advanced or metastatic GEP-NEC patients; octreotide LAR may be a good maintenance treatment and should be considered as a treatment option for these patients in the future.

ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas

“…Alternative regimens substituting carboplatin for cisplatin, or irinotecan for EP, have been validated in SCLC and seem at least equivalent in terms of efficacy in limited series of GEP NEC (table 1) [13,30,31,32,33,34,35], with different toxicity profiles. In the context of advanced stage SCLC, a randomized study conducted in Japan demonstrated that the combination of irinotecan and cisplatin (IP) was associated with improved overall survival as compared to the standard cisplatin and EP combination [36].…”

Irinotecan plus cisplatin followed by octreotide long-acting release maintenance treatment in advanced gastroenteropancreatic neuroendocrine carcinoma: IPO-NEC study

“…In our retrospective analysis of 16 advanced GEP-NEC patients treated with IP, the median PFS and OS were 5.5 and 10.6 months, respectively [17]. Recently, a retrospective Japanese multicenter analysis [25] showed that for patients with advanced NEC of the digestive system including gastrointestinal tract and hepato-biliary-pancreatic system treated with IP/EP ( n = 160/46), the ORR were 50%/28% and the median OS times were 13.0/7.3 months.…”

“…Our retrospective study has also revealed that the ORR of IP chemotherapy was 57.1 %, with a disease control rate of 78.6 % in advanced GEP-NEC patients [17]. Although quite chemo-sensitive, advanced GEP-NECs are always aggressive with short progression-free survival (PFS) and overall survival (OS) times.…”

“…In our retrospective study [17], octreotide long-acting release (LAR) was administered as maintenance treatment for patients in which the disease was controlled after an irinotecan/cisplatin regimen. All patients tolerated the octreotide LAR treatment well.…”

Review of recents advances in medical treatment for neuroendocrine neoplasms: somatostatin analogs and chemotherapy

“…The response rate was 51%, median PFS 5.5 months, and OS 10.6 months. [59] A further subgroup of patients with GEP NENs G3 (WHO 2010) is represented by morphologically well-differentiated neuroendocrine neoplasms while having Ki67 > 20% and/ or mitosis > 20/10 HPF. Recent reports suggest that these tumors have a better prognosis than other GEP NECs and are less responsive to conventional chemotherapies.…”