Systemic therapy for neuroendocrine tumours of gastroenteropancreatic origin

Abstract

Systemic therapy is one of a number of treatment options routinely used in the management of advanced, unresectable neuroendocrine tumours (NETs). In contrast to many of the other NET treatment modalities, there is at least some evidence base to justify its use. Even so, welldesigned clinical trials are limited, since conducting clinical research in this complex group of rare cancers is challenging. The remit of this review article is to summarise the oncology literature and explain the role of systemic therapy in treating NETs of gastroenteropancreatic origin, identifying benefits and limitations. The molecular biology of NETs is now being unravelled, which affords new opportunities for development of mechanism-driven therapies. The rationale for some of the newer systemic targeted therapies that are showing promise in the clinic is discussed.

Predictors of Long-Term Outcome in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors After Peptide Receptor Radionuclide Therapy with 177Lu-Octreotate

“…The median PFS was 25 mo (95% CI, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], and the median OS was 57 mo (95% CI, 48-66). These outcomes were notable and compared well with those achieved with other current treatment modalities (14,18,27,30,40). For nonpancreatic GEP NET, the regression rate (partial response plus minor response) was 39.1%.…”

“…However, even this "impaired" survival of patients with NET in the "upper" G2 range is encouraging (median PFS and OS of 19 and 34 mo, respectively). It appears to be at least equal to that achieved with other treatment modalities (14), with reported OS of 11-24 mo (well-differentiated metastatic GEP NET) and 7-27 mo (well-differentiated metastatic pancreatic NET). We are aware that we should be cautious when making comparisons with historic control groups; nevertheless, it is fair to state that even the presented outcome for the subgroup with an unfavorable prognosis (Ki-67 of .10%) still indicates effective treatment and clearly does not provide an argument against performing PRRT in this subgroup.…”

“…The overall response rates of 36.5% (partial response) and 54.1% (regression rate; partial response plus minor response) and the median PFS and OS (26 and 55 mo, respectively) are highly promising and compare favorably with those achieved with other treatment modalities (14)(15)(16)(17)(18). The data were analyzed in accordance with the new World Health Organization criteria (2010) and should help with comparisons of outcome data from different patient cohorts in various treatment studies.…”

“…Subsequent studies reported similar response rates after treatment with a temozolomide-based regimen (26)(27)(28)(29), with a median PFS of up to 18 mo. Recent trials evaluated a variety of novel targeted agents (14,17,18,(30)(31)(32)(33) with disappointing low response rates (,20%) for gastrointestinal NET. The outcomes proved significantly better than those of placebo-treated control groups with pancreatic NET; the median PFS in patients treated with sunitinib or everolimus was up to 12 mo (30,34).…”

A Case Report of a Poorly Differentiated Neuroendocrine Carcinoma Diagnosed in the Bone Marrow

“…Poorly differentiated neuroendocrine tumors show sensitivity to platinum and etoposide regimens, but overall their prognosis remains poor [7]. A phase II trial investigated the activity of combination chemotherapy with paclitaxel, carboplatin, and etoposide in patients with poorly differentiated or small cell neuroendocrine carcinoma of unknown primary site.…”