PMID- 26490655
OWN - NLM
STAT- MEDLINE
DCOM- 20160912
LR  - 20191210
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 33
IP  - 6
DP  - 2015 Dec
TI  - A phase I trial of mFOLFOX6 combined with the oral PI3K inhibitor BKM120 in 
      patients with advanced refractory solid tumors.
PG  - 1225-31
LID - 10.1007/s10637-015-0298-3 [doi]
AB  - PURPOSE: The oral PI3K inhibitor BKM120 has been reported as safe and well 
      tolerated in early phase clinical trials of advanced cancer patients. We 
      performed a phase I trial of BKM120 plus mFOLFOX6 (5-FU/LV + oxaliplatin), a 
      common chemotherapeutic backbone in GI malignancies, to establish the maximum 
      tolerated dose (MTD) and characterize the safety and tolerability of the 
      combination. METHODS: Patients with advanced solid tumors received oral BKM120 
      daily combined with standard doses of mFOLFOX6 every 2 weeks of a 28 day cycle. 
      The study utilized a standard 3 + 3 dose escalation schema. RESULTS: A total of 
      17 patients received treatment with BKM120, 13 of which were evaluate for dose 
      limited toxicity (DLT). The most common tumor types were colorectal cancer, 
      cholangiocarcinoma, pancreatic cancer and hepatocellular carcinoma. DLT included 
      grade 3 hyperglycemia, grade 3 AST/ALT elevation, grade 4 neutropenia and grade 4 
      thrombocytopenia. A total of 76 % of patients experienced treatment related grade 
      3/4 adverse events (AEs), the most common of which were neutropenia, fatigue, 
      leukopenia, hyperglycemia and thrombocytopenia. One patient demonstrated an 
      unconfirmed partial response and three patients had stable disease. DISCUSSION: 
      The MTD of BKM120 in combination with standard doses of mFOLFOX6 was 40 mg daily, 
      which is well below the 100 mg daily dose proven effective and tolerable both as 
      a single agent and in combination with other chemotherapeutics. In addition, the 
      regimen of BKM120 with mFOLFOX6 in patients with refractory solid tumors resulted 
      in increased toxicity than would be expected from either the PI3K inhibitor or 
      the chemotherapy backbone alone.
FAU - McRee, Autumn J
AU  - McRee AJ
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599, USA. 
      autumn_mcree@med.unc.edu.
FAU - Sanoff, Hanna K
AU  - Sanoff HK
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599, USA.
FAU - Carlson, Cheryl
AU  - Carlson C
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599, USA.
FAU - Ivanova, Anastasia
AU  - Ivanova A
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel 
      Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599, USA.
FAU - O'Neil, Bert H
AU  - O'Neil BH
AD  - Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
LA  - eng
GR  - K07 CA160722/CA/NCI NIH HHS/United States
GR  - K12 CA120780/CA/NCI NIH HHS/United States
GR  - 2K12CA120780-06/CA/NCI NIH HHS/United States
GR  - K07CA160722/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151021
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Aminopyridines)
RN  - 0 (Morpholines)
RN  - 0 (NVP-BKM120)
RN  - 0 (Organoplatinum Compounds)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - Folfox protocol
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aminopyridines/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Disease Progression
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Humans
MH  - Leucovorin/administration & dosage/adverse effects
MH  - Leukopenia/chemically induced
MH  - Male
MH  - Middle Aged
MH  - Morpholines/*administration & dosage/adverse effects
MH  - Nausea/chemically induced
MH  - Neoplasms/diagnosis/*drug therapy
MH  - Organoplatinum Compounds/administration & dosage/adverse effects
MH  - *Phosphoinositide-3 Kinase Inhibitors
PMC - PMC5907495
MID - NIHMS953656
OTO - NOTNLM
OT  - 5-fluorouracil
OT  - BKM120
OT  - Gastrointestinal malignancies
OT  - Oxaliplatin
OT  - PI3K pathway
COIS- Conflict of interest The remaining authors declare that they have no conflict of 
      interest.
EDAT- 2015/10/23 06:00
MHDA- 2016/09/13 06:00
PMCR- 2018/04/19
CRDT- 2015/10/23 06:00
PHST- 2015/09/22 00:00 [received]
PHST- 2015/10/15 00:00 [accepted]
PHST- 2015/10/23 06:00 [entrez]
PHST- 2015/10/23 06:00 [pubmed]
PHST- 2016/09/13 06:00 [medline]
PHST- 2018/04/19 00:00 [pmc-release]
AID - 10.1007/s10637-015-0298-3 [pii]
AID - 10.1007/s10637-015-0298-3 [doi]
PST - ppublish
SO  - Invest New Drugs. 2015 Dec;33(6):1225-31. doi: 10.1007/s10637-015-0298-3. Epub 
      2015 Oct 21.