PMID- 25300944
OWN - NLM
STAT- MEDLINE
DCOM- 20160412
LR  - 20211203
IS  - 1029-2403 (Electronic)
IS  - 1026-8022 (Linking)
VI  - 56
IP  - 6
DP  - 2015 Jun
TI  - Efficacy, safety, pharmacokinetics and pharmacodynamics of SAR245409 (voxtalisib, 
      XL765), an orally administered phosphoinositide 3-kinase/mammalian target of 
      rapamycin inhibitor: a phase 1 expansion cohort in patients with relapsed or 
      refractory lymphoma.
PG  - 1763-70
LID - 10.3109/10428194.2014.974040 [doi]
AB  - The maximum tolerated dose of SAR245409 (voxtalisib), a pan-class I 
      phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) 
      inhibitor, was determined in a phase 1 dose-escalation study in advanced solid 
      tumors. We report safety, pharmacokinetics (PK), pharmacodynamics and preliminary 
      efficacy of SAR245409 capsules 50 mg twice daily in an expansion cohort of 16 
      patients with relapsed/refractory lymphoma. The most common treatment-related 
      adverse events (AEs) were nausea (31.3%) and diarrhea (25.0%). The most common 
      grade 3/4 treatment-related AE was increased alanine aminotransferase (12.5%). PK 
      results were consistent with solid tumors, confirming a relatively short 
      steady-state half-life (mean 4.61 h). Among 12 evaluable patients, one complete 
      response and two partial responses were achieved in patients with and without 
      PI3K/mTOR pathway alterations. In a patient with mantle cell lymphoma achieving 
      PR, SAR245409 was associated with significant inhibition of PI3K/mTOR and 
      extracellular signal-related kinase (ERK) pathways. Preliminary efficacy warrants 
      further evaluation of SAR245409 in lymphoma.
FAU - Papadopoulos, Kyriakos P
AU  - Papadopoulos KP
AD  - South Texas Accelerated Research Therapeutics , San Antonio, TX , USA.
FAU - Egile, Coumaran
AU  - Egile C
FAU - Ruiz-Soto, Rodrigo
AU  - Ruiz-Soto R
FAU - Jiang, Jason
AU  - Jiang J
FAU - Shi, Weiliang
AU  - Shi W
FAU - Bentzien, Frauke
AU  - Bentzien F
FAU - Rasco, Drew
AU  - Rasco D
FAU - Abrisqueta, Pau
AU  - Abrisqueta P
FAU - Vose, Julie M
AU  - Vose JM
FAU - Tabernero, Josep
AU  - Tabernero J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141119
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Quinoxalines)
RN  - 0 (Sulfonamides)
RN  - 0 (XL765)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia/chemically induced
MH  - Area Under Curve
MH  - Diarrhea/chemically induced
MH  - Drug Resistance, Neoplasm
MH  - Exanthema/chemically induced
MH  - Female
MH  - Humans
MH  - Lymphoma/*drug therapy/pathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Nausea/chemically induced
MH  - Neoplasm Recurrence, Local
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Quinoxalines/adverse effects/pharmacokinetics/*therapeutic use
MH  - Remission Induction
MH  - Sulfonamides/adverse effects/pharmacokinetics/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - PI3K
OT  - lymphoma
OT  - mTOR
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - signaling therapies
EDAT- 2014/10/11 06:00
MHDA- 2016/04/14 06:00
CRDT- 2014/10/11 06:00
PHST- 2014/10/11 06:00 [entrez]
PHST- 2014/10/11 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
AID - 10.3109/10428194.2014.974040 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2015 Jun;56(6):1763-70. doi: 10.3109/10428194.2014.974040. Epub 
      2014 Nov 19.