Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms

Abstract

Forty-five patients with metastatic neuroendocrine tumors were treated with a regimen of etoposide 130 mg/m2/d for 3 days plus cisplatin 45 mg/m2/d on days 2 and 3. Both drugs were given by continuous intravenous infusion. Among 27 patients with well-differentiated carcinoid tumors or islet cell carcinomas, only two partial objective tumor regressions were observed (7%). Among 18 patients prospectively classified as having anaplastic neuroendocrine carcinomas, however, there were nine partial regressions and three complete regressions, an overall regression rate of 67%. For anaplastic disease, the median duration of regression was 8 months (range to 21 months). Tumor response was unrelated to primary site, endocrine hyperfunction, or prior therapy experience. The median survival of all patients with anaplastic tumors was 19 months; this seemed favorable when considering the small experiences with these rare tumors reported in the literature. Toxicity, which was severe for most patients, consisted primarily of vomiting, leukopenia, thrombocytopenia, anemia, alopecia, and neuropathy. The anaplastic neuroendocrine tumor is strongly responsive to therapy with combined etoposide and cisplatin. Patients with undifferentiated carcinomas, originating in typical neuroendocrine tumor sites (small and large bowel, pancreas, and stomach) or of unknown origin, who have consistent histologic findings by light microscopy should be evaluated for this possibility with appropriate immune staining or electron microscopy.

Are G3 ENETS neuroendocrine neoplasms heterogeneous?

“…For instance, the absence of midgut primaries and male predominance do not mirror classic metastatic low-grade well-differentiated GEP neoplasms in which ileum is the most frequent primary location and sex ratio is around one. This point is even better illustrated by the median OS of our patients, which is higher than the 8-month median OS usually observed in metastatic poorly differentiated NEC (Moertel et al 1991, Mitry et al 1999, Yamazaki et al 2005, Hainsworth et al 2006 but is still lower than expected for metastatic well-differentiated GEP-NEN, for which the 5-year survival is about 50% (Durante et al 2009.…”

“…In addition, the differentiation status constitutes a predictive factor of response to cisplatin-based chemotherapy (Mitry et al 1999, Pavel et al 2012. Several studies demonstrated that poorly differentiated NEN respond to cisplatin in more than 50% of cases against !15% for well-differentiated ones (Moertel et al 1991, Mitry et al 1999, Yamazaki et al 2005, Hainsworth et al 2006.…”

Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation

“…Several trials have investigated the effects of chemotherapy, SAAs (either octreotide on lanreotide), and biological response modifiers such as a-interferon in the treatment of these tumours, achieving conflicting results in term of response rate, symptom control, and survival (Kvols et al, 1986;Moertel et al, 1991;Di Bartolomeo et al, 1995;Jensen, 1997;Bajetta et al, 1998Bajetta et al, , 2000Bajetta et al, , 2003Bajetta et al, , 2005Rougier and Ducreux, 1999;Jensen and Doherty, 2001;Mitry and Rougier, 2001;Oberg, 2002;Faiss et al, 2003;Hainsworth et al, 2006), mainly due to the very difficult classification of these tumours and pathological analysis. Although equally able to control hormonal symptoms by reducing the secretion of biological amines and various peptides, these analogues exert a poor tumoricidal effect, being able to decrease tumour size in less than 15% of patients.…”

Extrapulmonary neuroendocrine small and large cell carcinomas: a review of controversial diagnostic and therapeutic issues

“…The first report on EPNEC therapy goes back to 1991 when Moertel and coworkers [68] firstly proposed platinum-etoposide regimens in NEC and identified a 67% response rate with a median survival of 19 months. These apparently excellent results were subsequently confirmed in 41 EPNEC patients who displayed a 42% response rate and a 15-month median survival [69].…”