title: A Phase Ib/II Study Evaluating the Combination of Weekly Docetaxel and Cisplatin Together with Capecitabine and Bevacizumab in Patients with Advanced Esophago-Gastric Cancer.
abstract: BACKGROUND
  Current treatment options for advanced esophagogastric cancer (AEGC) are still unsatisfactory. The aim of this prospective phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC.
  
  
  METHODS
  Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25-35 mg/m2, days 1,8, capecitabine 1,600 mg/m2 days 1-14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX (phase Ib part) and to determine the tumor response rate (phase II part).
  
  
  RESULTS
  The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%), usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. The recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). Hence, the objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. For the 17 patients treated at the MTD, the objective response rate was 41% and the disease control rate was 88%. The median overall survival (OS) for these patients was 13.9 months (range, 1.5-52.2 months) and the median progression-free survival was 7.6 months (range, 1.3-26.6 months). The 2-year OS rate reached 23.7%.
  
  
  CONCLUSIONS
  AVDCX was associated with a high rate of regimen related fatal adverse events and is not appropriate for further development in AEGC patients.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00845884.
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Baruch
authors.identifier: http://orcid.org/0000-0002-1596-9362
authors.initials: B
authors.lastname: Brenner
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Sarfaty
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Purim
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kundel
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Limor
authors.initials: L
authors.lastname: Amit
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Abramovich
authors.affiliation: Department of Radiology, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Udi
authors.initials: U
authors.lastname: Sadeh Gonik
authors.affiliation: Institute of Oncology, Kaplan Medical Center, Rehovot, and Hebrew Univerity, Jerusalem, Israel.
authors.forename: Efraim
authors.initials: E
authors.lastname: Idelevich
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Gordon
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Medalia
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petach Tiqva, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Sulkes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D000069287:Capecitabine; D002945:Cisplatin