PMID- 31852811
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 25
IP  - 5
DP  - 2020 May
TI  - Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 
      5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, 
      and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving 
      Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204).
PG  - e798-e807
LID - 10.1634/theoncologist.2019-0437 [doi]
AB  - BACKGROUND: The addition of bevacizumab to chemotherapy improved outcomes for 
      patients with metastatic colon cancer. E5204 was designed to test whether the 
      addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and 
      definitive surgery, could improve overall survival (OS) in patients with stage 
      II/III adenocarcinoma of the rectum. SUBJECTS, MATERIALS, AND METHODS: Patients 
      with stage II/III rectal cancer who had completed neoadjuvant 
      5-fluorouracil-based chemoradiation and had undergone complete resection were 
      enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with 
      bevacizumab (Arm B) administered every 2 weeks for 12 cycles. RESULTS: E5204 
      registered only 355 patients (17% of planned accrual goal) as it was terminated 
      prematurely owing to poor accrual. At a median follow-up of 72 months, there was 
      no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free 
      survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related 
      grade >/= 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a 
      higher proportion of patients who discontinued therapy early as a result of AEs 
      and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common 
      grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, 
      diarrhea (without prior colostomy), and fatigue. CONCLUSION: At 17% of its 
      planned accrual, E5204 did not meet its primary endpoint. The addition of 
      bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS 
      in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE: At 17% of 
      its planned accrual, E5204 was terminated early owing to poor accrual. At a 
      median follow-up of 72 months, there was no significant difference in 5-year 
      overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 
      76.5%) between the two arms. Despite significant advances in the treatment of 
      rectal cancer, especially in improving local control rates, the risk of distant 
      metastases and the need to further improve quality of life remain a challenge. 
      Strategies combining novel agents with chemoradiation to improve both distant and 
      local control are needed.
CI  - (c) AlphaMed Press 2019.
FAU - Chakravarthy, A Bapsi
AU  - Chakravarthy AB
AUID- ORCID: 0000-0003-2824-2514
AD  - Vanderbilt University Medical Center, Nashville, Tennessee, USA.
FAU - Zhao, Fengmin
AU  - Zhao F
AD  - ECOG-ACRIN Biostatistics Center, Boston, Massachusetts, USA.
FAU - Meropol, Neal J
AU  - Meropol NJ
AD  - Flatiron Health, New York, New York, USA.
AD  - Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, 
      Ohio, USA.
FAU - Flynn, Patrick J
AU  - Flynn PJ
AD  - Abbott-Northwestern Hospital, Minneapolis, Minnesota, USA.
FAU - Wagner, Lynne I
AU  - Wagner LI
AD  - Wake Forest University Health Sciences, Winston Salem, North Carolina, USA.
FAU - Sloan, Jeffrey
AU  - Sloan J
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Diasio, Robert B
AU  - Diasio RB
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Mitchell, Edith P
AU  - Mitchell EP
AD  - Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
FAU - Catalano, Paul
AU  - Catalano P
AD  - ECOG-ACRIN Biostatistics Center, Boston, Massachusetts, USA.
FAU - Giantonio, Bruce J
AU  - Giantonio BJ
AD  - Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
FAU - Catalano, Robert B
AU  - Catalano RB
AD  - Drexel University, Philadelphia, Pennsylvania, USA.
FAU - Haller, Daniel G
AU  - Haller DG
AD  - University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Awan, Rashid A
AU  - Awan RA
AD  - University of Pittsburgh Cancer Institute (UPCI), Johnstown, Pennsylvania, USA.
FAU - Mulcahy, Mary F
AU  - Mulcahy MF
AD  - Northwestern University, Chicago, Illinois, USA.
FAU - O'Brien, Timothy E
AU  - O'Brien TE
AD  - Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, 
      Ohio, USA.
FAU - Santala, Roger
AU  - Santala R
AD  - Montana Cancer Consortium, Billings, Montana, USA.
FAU - Cripps, Christine
AU  - Cripps C
AD  - Ottawa Health Research Institute-General Division, Ottawa, Ontario, Canada.
FAU - Weis, John R
AU  - Weis JR
AD  - Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah, USA.
FAU - Atkins, James N
AU  - Atkins JN
AD  - Southeast Cancer Control Consortium, Winston-Salem, North Carolina, USA.
FAU - Leichman, Cynthia G
AU  - Leichman CG
AD  - Laura and Issac Perlmutter Cancer Center at NYU Langone, New York, New York, USA.
FAU - Petrelli, Nicholas J
AU  - Petrelli NJ
AD  - Delaware/Christiana Care NCORP, Newark, Delaware, USA.
FAU - Sinicrope, Frank A
AU  - Sinicrope FA
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Brierley, James D
AU  - Brierley JD
AD  - University Health Network-Princess Margaret Hospital, Toronto, Ontario, Canada.
FAU - Tepper, Joel E
AU  - Tepper JE
AD  - University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
FAU - O'Dwyer, Peter J
AU  - O'Dwyer PJ
AD  - University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Sigurdson, Elin R
AU  - Sigurdson ER
AD  - Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
FAU - Hamilton, Stanley R
AU  - Hamilton SR
AD  - MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Cella, David
AU  - Cella D
AD  - Northwestern University, Chicago, Illinois, USA.
FAU - Benson, Al B 3rd
AU  - Benson AB 3rd
AD  - Northwestern University, Chicago, Illinois, USA.
LA  - eng
GR  - U10 CA180868/CA/NCI NIH HHS/United States
GR  - UG1 CA189867/CA/NCI NIH HHS/United States
GR  - U10 CA180821/CA/NCI NIH HHS/United States
GR  - UG1 CA189858/CA/NCI NIH HHS/United States
GR  - U10 CA180847/CA/NCI NIH HHS/United States
GR  - UG1 CA189863/CA/NCI NIH HHS/United States
GR  - U10 CA180818/CA/NCI NIH HHS/United States
GR  - UG1 CA189819/CA/NCI NIH HHS/United States
GR  - U10 CA180820/CA/NCI NIH HHS/United States
GR  - U10 CA180794/CA/NCI NIH HHS/United States
GR  - U10 CA180888/CA/NCI NIH HHS/United States
GR  - U10 CA180858/CA/NCI NIH HHS/United States
GR  - UG1 CA189872/CA/NCI NIH HHS/United States
GR  - UG1 CA189828/CA/NCI NIH HHS/United States
GR  - UG1 CA233373/CA/NCI NIH HHS/United States
GR  - U10 CA180863/CA/NCI NIH HHS/United States
GR  - U10 CA180790/CA/NCI NIH HHS/United States
GR  - U10 CA180867/CA/NCI NIH HHS/United States
GR  - U10 CA180838/CA/NCI NIH HHS/United States
GR  - U10 CA180853/CA/NCI NIH HHS/United States
GR  - U10 CA180844/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191218
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Organoplatinum Compounds)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Bevacizumab/therapeutic use
MH  - Chemotherapy, Adjuvant
MH  - Disease-Free Survival
MH  - *Fluorouracil/therapeutic use
MH  - Humans
MH  - Leucovorin/therapeutic use
MH  - Neoplasm Staging
MH  - Organoplatinum Compounds/therapeutic use
MH  - Oxaliplatin/therapeutic use
MH  - Quality of Life
MH  - *Rectal Neoplasms/drug therapy/radiotherapy
PMC - PMC7216434
OTO - NOTNLM
OT  - Adjuvant therapy
OT  - Antiangiogenesis
OT  - Avastin
OT  - Bevacizumab
OT  - Rectal cancer
COIS- Disclosures of potential conflicts of interest may be found at the end of this 
      article.
EDAT- 2019/12/20 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/05/01
CRDT- 2019/12/20 06:00
PHST- 2019/06/10 00:00 [received]
PHST- 2019/09/06 00:00 [accepted]
PHST- 2019/12/20 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2019/12/20 06:00 [entrez]
PHST- 2020/05/01 00:00 [pmc-release]
AID - theoncologist.2019-0437 [pii]
AID - ONCO13207 [pii]
AID - 10.1634/theoncologist.2019-0437 [doi]
PST - ppublish
SO  - Oncologist. 2020 May;25(5):e798-e807. doi: 10.1634/theoncologist.2019-0437. Epub 
      2019 Dec 18.