GEP–NETs UPDATE: Radionuclide therapy in neuroendocrine tumors

Abstract

Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs) patients. Most studies report objective response rates in 15-35% of patients. Also, outcome in terms of progression free survival (PFS) and overall survival compares very favorably with that for somatostatin analogs, chemotherapy, or new, 'targeted' therapies. They also compare favorably to PFS data for liverdirected therapies. Two decades after the introduction of PRRT, there is a growing need for randomized controlled trials comparing PRRT to 'standard' treatment, that is treatment with agents that have proven benefit when tested in randomized trials. Combining PRRT with liver-directed therapies or with targeted therapies could improve treatment results. The question to be answered, however, is whether a combination of therapies performed within a limited time-span from one another results in a better PFS than a strategy in which other therapies are reserved until after (renewed) tumor progression. Randomized clinical trials comparing PRRT with other treatment modalities should be undertaken to determine the best treatment options and treatment sequelae for patients with GEPNETs. European Journal of Endocrinology (2015) 172, R1-R8Invited Authors' profiles: Dik Kwekkeboom, MD works for the Department of Nuclear Medicine at the University Hospital, Erasmus MC, Rotterdam, The Netherlands. His major research interest is peptide receptor imaging and he coordinates the studies on therapy with the radiolabelled somatin analog 177 Lu-octreotate in patients with neuroendocrine tumors. He has numerous publications in international journals and textbooks, mainly in the field of endocrinology and peptide receptor scintigraphy and therapy.Wouter A van der Zwan currently works as research physician within the peptide receptor radionuclide therapy (PRRT) team at the Department of Nuclear Medicine of the Erasmus MC, Rotterdam and is directly involved in the treatment of patients affected by a Neuroendocrine Tumor with PRRT. Besides the clinical care of patients undergoing PRRT, his work includes conducting scientific research on the early and late effects, and optimization of PRRT. European Journal of EndocrinologyReview W A van der Zwan and others PRRT in neuroendocrine tumors 172:1 R1-R8

The efficacy of 177Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis

“…The indications for PRRT are relatively universal: unresectable NETs or distant metastatic disease [24]. High radiotracer uptake of tumour lesions on 111 In-octreotide scintigraphy or 68 Ga-somatostatin analogue positron emission tomography (PET) is a prerequisite for PRRT [21].…”

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas

“…However, given that these tumors frequently overexpress SSTR2, they often clinically respond to synthetic somatostatin analogs such as octreotide and lanreotide (16)(17)(18)(19). Indeed, diagnostic imaging studies of SSTR targets are standard for so-called "octreotide-avid" tumors (20), and peptidebased receptor radionuclide therapy also has been used to clinical effect (21). Thus, we reasoned that octreotide-targeted cellular transduction would enable the expression of tumor necrosis factor (TNF) within the SSTR2-expressing tumor cells after systemic administration through the vulnerable tumor-associated blood vessels of pancreatic NETs without off-target vascular or parenchymal toxicity to normal organs.…”

Tratamento de Tumores Neuroendócrinos Gastroenteropancreáticos com 177Lu-DOTA-TATE: Experiência do Instituto Português de Oncologia do Porto

“…[6][7][8][9] Num grande estudo retrospetivo que incluiu 504 doentes, Kwekkeboom et al descreveram casos graves de toxicidade hepática e síndrome mielodisplásico em < 1% dos doentes. 6 No presente estudo, registaram-se quatro casos de toxicidade hepática significativa (grau 3 CTCAE V.4) (13,3%).…”

“…9,10 Estes resultados são bastante promissores e superiores aos obtidos com outras terapêuticas médicas (Tabela 5). Na nossa análise os resultados em termos de tempo livre de progressão global de doença são concordantes com a literatura (25,6 meses) e superiores aos da literatura no grupo de doentes que apresentava lesões com elevada expressão de recetores da somatostatina (35,7 meses).…”