PMID- 24752410
OWN - NLM
STAT- MEDLINE
DCOM- 20141209
LR  - 20151119
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 120
IP  - 16
DP  - 2014 Aug 15
TI  - Everolimus in combination with octreotide long-acting repeatable in a first-line 
      setting for patients with neuroendocrine tumors: an ITMO group study.
PG  - 2457-63
LID - 10.1002/cncr.28726 [doi]
AB  - BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
CI  - (c) 2014 American Cancer Society.
FAU - Bajetta, Emilio
AU  - Bajetta E
AD  - Institute of Oncology, Polyclinic Hospital, Monza, Italy.
FAU - Catena, Laura
AU  - Catena L
FAU - Fazio, Nicola
AU  - Fazio N
FAU - Pusceddu, Sara
AU  - Pusceddu S
FAU - Biondani, Pamela
AU  - Biondani P
FAU - Blanco, Giusi
AU  - Blanco G
FAU - Ricci, Sergio
AU  - Ricci S
FAU - Aieta, Michele
AU  - Aieta M
FAU - Pucci, Francesca
AU  - Pucci F
FAU - Valente, Monica
AU  - Valente M
FAU - Bianco, Nadia
AU  - Bianco N
FAU - Mauri, Chiara Maria
AU  - Mauri CM
FAU - Spada, Francesca
AU  - Spada F
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20140418
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 9HW64Q8G6G (Everolimus)
RN  - RWM8CCW8GP (Octreotide)
RN  - W36ZG6FT64 (Sirolimus)
RN  - Gastro-enteropancreatic neuroendocrine tumor
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Intestinal Neoplasms/*drug therapy/pathology
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Neuroendocrine Tumors/*drug therapy/pathology
MH  - Octreotide/administration & dosage
MH  - Pancreatic Neoplasms/*drug therapy/pathology
MH  - Sirolimus/administration & dosage/analogs & derivatives
MH  - Stomach Neoplasms/*drug therapy/pathology
OTO - NOTNLM
OT  - everolimus
OT  - neuroendocrine tumor
OT  - octreotide long-acting repeatable
EDAT- 2014/04/23 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/04/23 06:00
PHST- 2014/01/21 00:00 [received]
PHST- 2014/02/27 00:00 [revised]
PHST- 2014/02/28 00:00 [accepted]
PHST- 2014/04/23 06:00 [entrez]
PHST- 2014/04/23 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1002/cncr.28726 [doi]
PST - ppublish
SO  - Cancer. 2014 Aug 15;120(16):2457-63. doi: 10.1002/cncr.28726. Epub 2014 Apr 18.