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Bevacizumab Added to Moderate-dose Chemotherapy for Refractory Uterine Cancer.

Abstract Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs.
PMID
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Authors

Mayor MeshTerms
Keywords

Targeted therapy

bevacizumab

chemotherapy safety

endometrial cancer

resistance

Journal Title anticancer research
Publication Year Start




PMID- 29277822
OWN - NLM
STAT- In-Process
LR  - 20171226
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 38
IP  - 1
DP  - 2018 Jan
TI  - Bevacizumab Added to Moderate-dose Chemotherapy for Refractory Uterine Cancer.
PG  - 547-552
AB  - BACKGROUND/AIM: Bevacizumab (bev), when added to a moderate dose combination of
      previously failed cytotoxins, as a third- and fourth-line therapy for refractory 
      gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality
      responses. The regimen was based on preclinical models designed in order to
      simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic
      drugs. PATIENTS AND METHODS: Eligible patients (n=9) had high-grade endometrial
      tumors and had failed standard chemotherapy. Bev (10 mg/kg every 2 weeks) and
      cyclophosphamide (150-250 mg/m(2)), were added to a combination of gemcitabine,
      fluorouracil, leucovorin, irinotecan and a platinum analogue -first without and
      then with docetaxel- each at approximately 1/2 to 1/3 of their standard dosage.
      Dose modification aimed at a repeated absolute neutrophil count (ANC) of
      750-1,500 mul or platelets of 125,000-75,000 mul. Safety measures included
      stop-go use (intermittent, as needed, brief withholding of bev with resumption
      when again tolerated), of bev, and both prospective and ongoing dose modification
      in order to protect the bowels. RESULTS: Induction treatment was free of
      life-threatening complications. Nine consecutive patients, 3 under second- and 6 
      under multi-line treatment, had 9 objective responses and 8 produced long
      clinical benefits, 2 of which were complete responses. Seven responses created
      opportunities for personalized added treatment and research. Absolute median
      survival was 21.5 months for the 8 patients with platinum-resistant tumors. One
      patient was unable to tolerate a first standard adjuvant dose of paclitaxel.
      After rapid peritoneal progression of disease, treatment has produced 52+ months 
      of unmaintained complete remission. CONCLUSION: Bev, in the combination that was 
      used in this study, meets response, survival, and toxicity criteria for further
      testing against second- or multi-line chemotherapy-resistant tumors and also when
      a standard treatment is not safe.
CI  - Copyright(c) 2018, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Bruckner, Howard W
AU  - Bruckner HW
AD  - MZB Foundation for Cancer Research, New York, NY, U.S.A.
      [email protected]
AD  - Bruckner Oncology, New York, NY, U.S.A.
FAU - Gurell, Daniel
AU  - Gurell D
AD  - Department of Radiology, University Diagnostic Medical Imaging, New York, U.S.A.
FAU - Hirschfeld, Azriel
AU  - Hirschfeld A
AD  - MZB Foundation for Cancer Research, New York, NY, U.S.A.
AD  - Bruckner Oncology, New York, NY, U.S.A.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
OTO - NOTNLM
OT  - Targeted therapy
OT  - bevacizumab
OT  - chemotherapy safety
OT  - endometrial cancer
OT  - resistance
EDAT- 2017/12/27 06:00
MHDA- 2017/12/27 06:00
CRDT- 2017/12/27 06:00
PHST- 2017/08/03 00:00 [received]
PHST- 2017/10/23 00:00 [revised]
PHST- 2017/10/30 00:00 [accepted]
PHST- 2017/12/27 06:00 [entrez]
PHST- 2017/12/27 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
AID - 38/1/547 [pii]
PST - ppublish
SO  - Anticancer Res. 2018 Jan;38(1):547-552.