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Targeted Therapy for Resistant Cholangiocarcinoma with Bevacizumab or Cetuximab Added to Failed Cytotoxic Drug Cores.

Abstract Addition of bevacizumab/targeted therapy to cores consisting of four to five previously failed cytotoxic drugs employed at low/moderate dosages has produced third- and fourth-line regression of refractory gastric and ovarian cancer. Targeted therapy added to cores of previously failed drugs has similarly produced responses of refractory pancreatic cancer.
PMID
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Authors

Mayor MeshTerms
Keywords

Bevacizumab

cetuximab

cholangiocarcinoma

drug resistance

low-dose cytotoxins

Journal Title anticancer research
Publication Year Start




PMID- 26722072
OWN - NLM
STAT- MEDLINE
DCOM- 20160512
LR  - 20160101
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 36
IP  - 1
DP  - 2016 Jan
TI  - Targeted Therapy for Resistant Cholangiocarcinoma with Bevacizumab or Cetuximab
      Added to Failed Cytotoxic Drug Cores.
PG  - 399-402
AB  - BACKGROUND: Addition of bevacizumab/targeted therapy to cores consisting of four 
      to five previously failed cytotoxic drugs employed at low/moderate dosages has
      produced third- and fourth-line regression of refractory gastric and ovarian
      cancer. Targeted therapy added to cores of previously failed drugs has similarly 
      produced responses of refractory pancreatic cancer. PATIENTS AND METHODS: The aim
      of the present study was to evaluate the addition of targeted therapy to failed
      cores for patients with end-stage disease. Patients all had end-stage measurable 
      cholangiocarcinoma and active progression during treatment with cores. Targeted
      therapy, bevacizumab or cetuximab, at standard dosages and schedule was added to 
      the failed cores, which consisted of: gemcitabine, fluorouracil, leucovorin and
      irinotecan on day 1, and a platin with/without docetaxel on day 2, each at its
      prior dose and schedule. Electronic medical records facilitated identification of
      patients for intent-to-treat analysis. RESULTS: All 13 patients had measurable
      disease; all standard cytotoxins had been used and failed before the start of
      treatment with targeted therapy added to the cores. The response rates according 
      to the Response Evaluation Criteria in Solid Tumors and response duration range
      were: bevacizumab cores: 3/6, 6 to 19 months, and cetuximab cores: 5/7, 10 to 28 
      months. Responses produced clinical benefit and one late neoadjuvant R0
      resection. There were no limiting hematological adverse events due to the cores. 
      Limiting adverse events were hypertension in two patients and an easily
      controlled duodenal ulcer in one. CONCLUSION: Bevacizumab cores and cetuximab
      cores both produced response rates which satisfy phase II criteria for further
      investigation. As cores, failed cytotoxic drugs, many at one-quarter to half of
      their standard doses have been found to produce synergistic benefit in
      combination with targeted therapy for end-stage patients in four diseases.
      Co-treatment with no longer active cytotoxic core drugs can demonstrate efficacy 
      attributable to the targeted therapy. This approach is a worthy, cost-effective
      fast-track registration strategy and distinctly different from trials testing
      primary treatment.
CI  - Copyright(c) 2016 International Institute of Anticancer Research (Dr. John G.
      Delinassios), All rights reserved.
FAU - Bruckner, Howard W
AU  - Bruckner HW
AD  - MZB Foundation for Cancer Research, New York, NY, U.S.A.
      [email protected]
FAU - Hirschfeld, Azriel
AU  - Hirschfeld A
AD  - Bruckner Oncology, Bronx, NY, U.S.A.
FAU - Schwartz, Myron
AU  - Schwartz M
AD  - Department of Surgery, Mount Sinai School of Medicine, New York, NY, U.S.A.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Bevacizumab/administration & dosage/*therapeutic use
MH  - Cetuximab/administration & dosage/*therapeutic use
MH  - Cholangiocarcinoma/*drug therapy
MH  - Humans
OTO - NOTNLM
OT  - Bevacizumab
OT  - cetuximab
OT  - cholangiocarcinoma
OT  - drug resistance
OT  - low-dose cytotoxins
EDAT- 2016/01/02 06:00
MHDA- 2016/05/14 06:00
CRDT- 2016/01/02 06:00
PHST- 2016/01/02 06:00 [entrez]
PHST- 2016/01/02 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
AID - 36/1/399 [pii]
PST - ppublish
SO  - Anticancer Res. 2016 Jan;36(1):399-402.