An open label, single arm, phase II study of combination RAD001 and octreotide LAR in patients with advanced neuroendocrine tumors as first line treatment
Nel gennaio 2009 è stato avviato uno studio sui tumori neuroendocrini
Lo studio (Protocollo N°03/2008) ha l’obiettivo di valutare se RAD001, in associazione a Octreotide LAR, rappresenti un trattamento efficace e ben tollerato in pazienti ai quali è stato diagnosticato un tumore carcinoide in stadio avanzato e quindi se RAD001 può ridurne o rallentarne la crescita.
Lo studio è stato chiuso al reclutamento nel giugno 2010. Sono stati arruolati 50 pazienti. Follow-up terminato nel giugno 2015.
Centri partecipanti :
- Fondazione IRCCS Istituto Nazionale Tumori, MILANO
- IEO Istituto Europeo di Oncologia, MILANO
- Ospedale Oncologico Regionale di RIONERO IN VULTURE (PZ)
- Azienda Ospedaliero-Universitaria di PARMA
- IRCCS Ospedale Casa Sollievo della Sofferenza, S.GIOVANNI ROTONDO (FG)
- Policlinico Universitario, MONSERRATO (CA)
- Istituto Oncologico, BARI
- Ospedale S. Chiara, PISA
- Istituto Oncologico del Mediterraneo, CATANIA
- IFO/IRE Istituto Regina Elena, ROMA
- Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study.
(Bajetta E, Catena L, Fazio N, Pusceddu S, Biondani P, Blanco G, Ricci S, Aieta M, Pucci F, Valente M, Bianco N, Mauri CM, Spada F).
Cancer. 2014 Aug 15;120(16):2457-63. doi: 10.1002/cncr.28726. Epub 2014 Apr 18.
Preclinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors. The activity and safety of everolimus was assessed in combination with octreotide long-acting repeatable (LAR) in patients with neuroendocrine tumors (NETs) of gastroenteropancreatic and lung origin.
This was a phase 2, multicenter trial using a Simon’s 2-stage minimax design. Treatment-naive patients with advanced well-differentiated NETs of gastroenteropancreatic tract and lung origin received everolimus 10 mg daily, in combination with octreotide LAR 30 mg every 28 days. The primary endpoint was objective response rate (ORR).
A total of 50 patients (median age, 60.5 years) were enrolled. Primary tumor sites were: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum and duodenum (2 patients), and unknown (14 patients). Thirteen patients (26%) had carcinoid syndrome. Treatment-related adverse events (AEs) were mostly grade 1 or 2; the only grade 4 AE was mucositis in 1 patient, whereas grade 3 AEs included skin rash in 1 case (2%), stomatitis in 4 cases (8%), and diarrhea in 11 cases (22%). The ORR was 18%; 2% of patients had a complete response (CR), 16% a partial response (PR) and 74% achieved stable disease (SD). All CRs and all PRs as well as 92% of SDs had a duration ≥ 6 months. The clinical benefit (CR+PR+SD) was 92%. At a median follow-up of 277 days, median time to progression and overall survival were not reached.
The everolimus-octreotide LAR combination was active and well tolerated in these previously treated patients with advanced NETs, suggesting a possible role as first-line treatment in patients with NET.
everolimus; neuroendocrine tumor; octreotide long-acting repeatable
PMID: 24752410 [PubMed – indexed for MEDLINE]
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