PMID- 24827133
OWN - NLM
STAT- MEDLINE
DCOM- 20151116
LR  - 20200206
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 25
IP  - 8
DP  - 2014 Aug
TI  - Activity and safety of RAD001 (everolimus) in patients affected by biliary tract 
      cancer progressing after prior chemotherapy: a phase II ITMO study.
PG  - 1597-603
LID - 10.1093/annonc/mdu175 [doi]
AB  - BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the 
      best available therapy remains undetermined. The mammalian target of rapamycin 
      (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical 
      evidence indicates that mTOR inhibition may be effective in the treatment of BTC. 
      We sought to evaluate the activity and tolerability of the mTOR inhibitor 
      RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. 
      PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 
      2008-007152-94) conducted in eight sites in Italy. Patients with locally 
      advanced, metastatic or recurrent BTC progressing despite previous chemotherapy 
      received a daily oral dose of everolimus 10 mg administered continuously in 
      28-day cycles. The two primary end points were disease control rate (DCR) and 
      objective response rate (ORR). Secondary end points were progression-free 
      survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: 
      Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One 
      patient showed a partial response at 2 months and one patient showed a complete 
      response sustained up to 8 months. The median (95% confidence interval) PFS was 
      3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP 
      was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), 
      thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of 
      mild-to-moderate severity. Two patients required dose reduction due to adverse 
      events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and 
      encouraging anti-tumour activity. Further trials are needed to establish the role 
      of everolimus in the treatment of BTC. EUDRACT 2008-007152-94.
CI  - (c) The Author 2014. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Buzzoni, R
AU  - Buzzoni R
AD  - Day Hospital/Outpatient Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 
      Milan.
FAU - Pusceddu, S
AU  - Pusceddu S
AD  - Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 
      sara.pusceddu@istitutotumori.mi.it.
FAU - Bajetta, E
AU  - Bajetta E
AD  - Medical Oncology Unit, Policlinico of Monza, Monza.
FAU - De Braud, F
AU  - De Braud F
AD  - Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
FAU - Platania, M
AU  - Platania M
AD  - Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
FAU - Iannacone, C
AU  - Iannacone C
AD  - Biostatistician LB Research srl, Cantu.
FAU - Cantore, M
AU  - Cantore M
AD  - Medical Oncology Unit, Asl 1, Massa Carrara.
FAU - Mambrini, A
AU  - Mambrini A
AD  - Medical Oncology Unit, Asl 1, Massa Carrara.
FAU - Bertolini, A
AU  - Bertolini A
AD  - Medical Oncology Unit, Presidio Ospedaliero Sondrio, Sondrio.
FAU - Alabiso, O
AU  - Alabiso O
AD  - Medical Oncology Unit, A.U.O. Maggiore della Carita, Novara.
FAU - Ciarlo, A
AU  - Ciarlo A
AD  - Medical Oncology Unit, Usl 4, Presidio Ospedaliero, Prato.
FAU - Turco, C
AU  - Turco C
AD  - Medical Oncology Unit, Italian Trials in Medical Oncology (ITMO) Group, 
      Fondazione IRCCS Istituto Nazionale Tumori, Milan.
FAU - Mazzaferro, V
AU  - Mazzaferro V
AD  - Gastro-Intestinal Surgery, Liver Transplantation and Hepatology Unit, Fondazione 
      IRCCS Istituto Nazionale Tumori, Milan, Italy.
LA  - eng
SI  - EudraCT/2008-007152-94
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20140514
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Organoplatinum Compounds)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
RN  - gemcitabine-oxaliplatin regimen
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biliary Tract Neoplasms/*drug therapy/mortality/pathology
MH  - Chemotherapy, Adjuvant
MH  - Deoxycytidine/analogs & derivatives/therapeutic use
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Organoplatinum Compounds/therapeutic use
MH  - Quality of Life
MH  - Sirolimus/*analogs & derivatives/therapeutic use
MH  - Survival Analysis
OTO - NOTNLM
OT  - advanced biliary tract cancer
OT  - everolimus
OT  - mTOR
EDAT- 2014/05/16 06:00
MHDA- 2015/11/17 06:00
CRDT- 2014/05/16 06:00
PHST- 2014/05/16 06:00 [entrez]
PHST- 2014/05/16 06:00 [pubmed]
PHST- 2015/11/17 06:00 [medline]
AID - S0923-7534(19)34815-X [pii]
AID - 10.1093/annonc/mdu175 [doi]
PST - ppublish
SO  - Ann Oncol. 2014 Aug;25(8):1597-603. doi: 10.1093/annonc/mdu175. Epub 2014 May 14.