PMID- 23942080
OWN - NLM
STAT- MEDLINE
DCOM- 20131115
LR  - 20211021
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 109
IP  - 5
DP  - 2013 Sep 3
TI  - A multicenter phase 1 study of PX-866 in combination with docetaxel in patients 
      with advanced solid tumours.
PG  - 1085-92
LID - 10.1038/bjc.2013.474 [doi]
AB  - BACKGROUND: This phase I, dose-finding study determined the safety, maximum 
      tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics, and 
      antitumour activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, 
      combined with docetaxel in patients with incurable solid tumours. METHODS: PX-866 
      was administered at escalating doses (4-8 mg daily) with docetaxel 75 mg m(-)(2) 
      intravenously every 21 days. Archived tumour tissue was assessed for potential 
      predictive biomarkers. RESULTS: Forty-three patients were enrolled. Most adverse 
      events (AEs) were grade 1 or 2. The most frequent study drug-related AE was 
      diarrhoea (76.7%), with gastrointestinal disorders occurring in 79.1% 
      (docetaxel-related) and 83.7% (PX-866-related). No dose-limiting toxicities were 
      observed. The RP2D was 8 mg, the same as the single-agent MTD. Co-administration 
      of PX-866 and docetaxel did not affect either drug's PKs. Best responses in 35 
      evaluable patients were: 2 partial responses (6%), 22 stable disease (63%), and 
      11 disease progression (31%). Eleven patients remained on study for >180 days, 
      including 8 who maintained disease control on single-agent PX-866. Overall median 
      progression-free survival (PFS) was 73.5 days (range: 1-569). A non-significant 
      association between longer PFS for PIK3CA-MUT/KRAS-WT vs PIK3CA-WT/KRAS-WT was 
      observed. CONCLUSION: Treatment with PX-866 and docetaxel was well tolerated, 
      without evidence of overlapping/cumulative toxicity. Further investigation with 
      this combination is justified.
FAU - Bowles, D W
AU  - Bowles DW
AD  - Division of Medical Oncology, School of Medicine, Universitiy of Colorado, 12801 
      E. 17th Avenue, MS 8117, Aurora, CO 80045, USA.
FAU - Ma, W W
AU  - Ma WW
FAU - Senzer, N
AU  - Senzer N
FAU - Brahmer, J R
AU  - Brahmer JR
FAU - Adjei, A A
AU  - Adjei AA
FAU - Davies, M
AU  - Davies M
FAU - Lazar, A J
AU  - Lazar AJ
FAU - Vo, A
AU  - Vo A
FAU - Peterson, S
AU  - Peterson S
FAU - Walker, L
AU  - Walker L
FAU - Hausman, D
AU  - Hausman D
FAU - Rudin, C M
AU  - Rudin CM
FAU - Jimeno, A
AU  - Jimeno A
LA  - eng
GR  - P30 CA046934/CA/NCI NIH HHS/United States
GR  - UL1 TR000128/TR/NCATS NIH HHS/United States
GR  - P30CA046934/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130813
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Gonanes)
RN  - 0 (PX-866)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
SB  - IM
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Biomarkers, Tumor/blood
MH  - Disease-Free Survival
MH  - Docetaxel
MH  - Female
MH  - Gonanes/adverse effects/*therapeutic use
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Taxoids/adverse effects/*therapeutic use
MH  - Treatment Outcome
PMC - PMC3778312
EDAT- 2013/08/15 06:00
MHDA- 2013/11/16 06:00
PMCR- 2014/09/03
CRDT- 2013/08/15 06:00
PHST- 2013/04/30 00:00 [received]
PHST- 2013/06/23 00:00 [revised]
PHST- 2013/07/23 00:00 [accepted]
PHST- 2013/08/15 06:00 [entrez]
PHST- 2013/08/15 06:00 [pubmed]
PHST- 2013/11/16 06:00 [medline]
PHST- 2014/09/03 00:00 [pmc-release]
AID - bjc2013474 [pii]
AID - 10.1038/bjc.2013.474 [doi]
PST - ppublish
SO  - Br J Cancer. 2013 Sep 3;109(5):1085-92. doi: 10.1038/bjc.2013.474. Epub 2013 Aug 
      13.