PMID- 33984725
OWN - NLM
STAT- MEDLINE
DCOM- 20210629
LR  - 20210629
IS  - 1872-7654 (Electronic)
IS  - 0301-2115 (Linking)
VI  - 262
DP  - 2021 Jul
TI  - Postoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance 
      bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: A phase 
      II AGOG/TGOG trial.
PG  - 13-20
LID - S0301-2115(21)00186-X [pii]
LID - 10.1016/j.ejogrb.2021.04.017 [doi]
AB  - OBJECTIVE: The objective of this study is to evaluate the safety and efficacy of 
      adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab 
      maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery 
      (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer. STUDY 
      DESIGN: This phase II clinical trial using Simon's minimax two-stage design was 
      conducted. At the first stage, 13 subjects were enrolled, and the trial would 
      proceed to second stage if </=3 subjects discontinued treatment for study-defined 
      significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and 
      primary peritoneal cancer deemed not feasible for primary cytoreductive surgery 
      were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC 
      could be either weekly paclitaxel (80 mg/m(2)) (dose-dense) plus 3-weekly 
      carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative 
      dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 
      3-weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 
      3-weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles. 
      RESULTS: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. 
      Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE 
      occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median 
      progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 
      13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 
      33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was 
      significant for PFS (>12 vs </= 12: p = 0.003). One of the 22 subjects did not 
      receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs 
      included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. 
      Study-defined significant AEs of bowel perforation, poor-healing wound, and 
      hypertension were found in 1 case each, respectively. CONCLUSION: This phase II 
      trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with 
      bevacizumab maintenance after NAC was feasible with tolerable toxicity and 
      comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase 
      or dose-dense scheduling throughout.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Chou, Hung-Hsueh
AU  - Chou HH
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan.
FAU - Chen, Wei-Chun
AU  - Chen WC
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan; Department of Obstetrics and Gynecology, Chang 
      Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan.
FAU - Yang, Lan-Yan
AU  - Yang LY
AD  - Clinical Trial Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, 
      Taiwan.
FAU - Huang, Huei-Jean
AU  - Huang HJ
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan.
FAU - Chang, Wei-Yang
AU  - Chang WY
AD  - Clinical Trial Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, 
      Taiwan.
FAU - Lin, Hao
AU  - Lin H
AD  - Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, 
      Chang Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Wu, Ren-Chin
AU  - Wu RC
AD  - Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Taoyuan, Taiwan.
FAU - Chen, Min-Yu
AU  - Chen MY
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan.
FAU - Qiu, J Timothy
AU  - Qiu JT
AD  - Department of Obstetrics and Gynecology, Taipei Medical University Hospital, 
      Taipei, Taiwan; International Ph.D. Program for Cell Therapy and Regeneration 
      Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
FAU - Huang, Kuan-Gen
AU  - Huang KG
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan.
FAU - Chao, Angel
AU  - Chao A
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan.
FAU - Chang, Ting-Chang
AU  - Chang TC
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan.
FAU - Lai, Chyong-Huey
AU  - Lai CH
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou 
      and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic 
      Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang 
      Gung University, Taoyuan, Taiwan. Electronic address: sh46erry@ms6.hinet.net.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20210418
PL  - Ireland
TA  - Eur J Obstet Gynecol Reprod Biol
JT  - European journal of obstetrics, gynecology, and reproductive biology
JID - 0375672
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Bevacizumab/therapeutic use
MH  - Carboplatin/therapeutic use
MH  - Carcinoma, Ovarian Epithelial/pathology
MH  - Chemotherapy, Adjuvant
MH  - Female
MH  - Humans
MH  - *Neoadjuvant Therapy
MH  - Neoplasm Staging
MH  - *Ovarian Neoplasms/pathology
MH  - Paclitaxel
OTO - NOTNLM
OT  - Dose-dense chemotherapy
OT  - Interval cytoreduction surgery
OT  - Neoadjuvant chemotherapy
OT  - Ovarian cancer
COIS- Declaration of Competing Interest Lai CH, Lin H and Qiu JT report free 
      bevacizumab supply from Roche for this trial. Lai CH reports honorarium from ACT 
      Genomics.
EDAT- 2021/05/14 06:00
MHDA- 2021/06/30 06:00
CRDT- 2021/05/13 20:25
PHST- 2021/02/12 00:00 [received]
PHST- 2021/04/02 00:00 [revised]
PHST- 2021/04/15 00:00 [accepted]
PHST- 2021/05/14 06:00 [pubmed]
PHST- 2021/06/30 06:00 [medline]
PHST- 2021/05/13 20:25 [entrez]
AID - S0301-2115(21)00186-X [pii]
AID - 10.1016/j.ejogrb.2021.04.017 [doi]
PST - ppublish
SO  - Eur J Obstet Gynecol Reprod Biol. 2021 Jul;262:13-20. doi: 
      10.1016/j.ejogrb.2021.04.017. Epub 2021 Apr 18.