PMID- 26335608
OWN - NLM
STAT- MEDLINE
DCOM- 20151203
LR  - 20240323
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 113
IP  - 6
DP  - 2015 Sep 15
TI  - Upfront FOLFOXIRI+bevacizumab followed by fluoropyrimidin and bevacizumab 
      maintenance in patients with molecularly unselected metastatic colorectal cancer.
PG  - 872-7
LID - 10.1038/bjc.2015.299 [doi]
AB  - BACKGROUND: The addition of bevacizumab (BEV) to standard doublet chemotherapy 
      improves outcomes compared with chemotherapy alone in patients with metastatic 
      colorectal cancer (mCRC). The OPAL study examined the effect of BEV+FOLFOXIRI 
      followed by 5FU/LV and BEV maintenance on progression-free survival (PFS) in 
      patients with previously untreated unresectable mCRC. METHODS: Eligible patients 
      had histologically confirmed mCRC, ECOG performance status ⩽1 and were 18-70 
      years old. Patients received up to 12 cycles of FOLFOXIRI+BEV q2w (induction 
      phase) followed by up to ⩽40 cycles of 5FU/LV+BEV q2w (maintenance phase). Median 
      PFS was the primary end point; secondary end points included response, OS, 
      secondary resection rate, safety and prognostic value of pharmacogenetic 
      profiling. RESULTS: Ninety-seven patients were enrolled. Of these, 90 received 
      study medication and formed the safety population: 64 males; median age 58 (range 
      28-71) years; ECOG performance status 0/1 in 54%/46% patients; and liver only 
      disease in 35 patients. Relative dose intensities were 79-85% for all four drugs. 
      The incidence of adverse events (AEs) was as previously reported and there were 
      no new safety signals. In total, 87 serious AEs occurred in 39 patients (43%). 
      Median PFS was 11.1 months (95% CI 9.4-12.0) and did thus not meet the primary 
      objective of 12 months. Median OS was 32.2 months (95% CI 22.6-36.9). Fifty-two 
      patients were pharmacogenetically profiled. CONCLUSIONS: FOLFOXIRI+BEV was 
      feasible in this molecularly unselected mCRC patient population, showing a high 
      efficacy in terms of survival, overall response and secondary resection rate. 
      Pharmacogenomic profiling revealed no clinically relevant marker.
FAU - Stein, Alexander
AU  - Stein A
AD  - University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, 
      Germany.
FAU - Atanackovic, Djordje
AU  - Atanackovic D
AD  - University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, 
      Germany.
FAU - Hildebrandt, Bert
AU  - Hildebrandt B
AD  - Charite Universitatsmedizin Berlin, Campus Charite Mitte, Chariteplatz 1, Berlin 
      10117, Germany.
FAU - Stubs, Patrick
AU  - Stubs P
AD  - University Hospital Magdeburg, Leipziger Strasse 44, Magdeburg 39120, Germany.
FAU - Brugger, Wolfram
AU  - Brugger W
AD  - Schwarzwald-Baar Klinikum, Klinikstrasse 11, Villingen-Schwenningen 78052, 
      Germany.
FAU - Hapke, Gunnar
AU  - Hapke G
AD  - Marienkrankenhaus, Alfredstrasse 9, Hamburg 22087, Germany.
FAU - Steffens, Claus-Christoph
AU  - Steffens CC
AD  - MVZ Hamatologie/Onkologie Klinik Dr Hancken, Harsefelder Str. 8, Stade 21680, 
      Germany.
FAU - Illerhaus, Gerald
AU  - Illerhaus G
AD  - Klinikum Stuttgart, Kriegsbergstrasse 60, Stuttgart 70174, Germany.
FAU - Bluemner, Ernst
AU  - Bluemner E
AD  - Ecron Acunova GmbH, Hahnstrasse 70, Frankfurt 60528, Germany.
FAU - Stohlmacher, Jan
AU  - Stohlmacher J
AD  - Tumorgenetik Bonn, Maximilianstrasse 28d, Bonn 53111, Germany.
FAU - Bokemeyer, Carsten
AU  - Bokemeyer C
AD  - University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, 
      Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT00940303
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150903
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Organoplatinum Compounds)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 7673326042 (Irinotecan)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - XT3Z54Z28A (Camptothecin)
RN  - FOLFOXIRI protocol
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Bevacizumab/*administration & dosage/adverse effects
MH  - Camptothecin/administration & dosage/adverse effects/analogs & derivatives
MH  - Colorectal Neoplasms/*drug therapy/genetics/mortality
MH  - Disease-Free Survival
MH  - Feasibility Studies
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Genes, ras
MH  - Humans
MH  - Induction Chemotherapy/methods
MH  - Irinotecan
MH  - Leucovorin/administration & dosage/adverse effects
MH  - Maintenance Chemotherapy/methods
MH  - Male
MH  - Middle Aged
MH  - Organoplatinum Compounds/administration & dosage/adverse effects
MH  - Oxaliplatin
MH  - Severity of Illness Index
PMC - PMC4578090
EDAT- 2015/09/04 06:00
MHDA- 2015/12/15 06:00
PMCR- 2016/09/15
CRDT- 2015/09/04 06:00
PHST- 2015/04/12 00:00 [received]
PHST- 2015/07/02 00:00 [revised]
PHST- 2015/07/27 00:00 [accepted]
PHST- 2015/09/04 06:00 [entrez]
PHST- 2015/09/04 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2016/09/15 00:00 [pmc-release]
AID - bjc2015299 [pii]
AID - 10.1038/bjc.2015.299 [doi]
PST - ppublish
SO  - Br J Cancer. 2015 Sep 15;113(6):872-7. doi: 10.1038/bjc.2015.299. Epub 2015 Sep 
      3.