title: S-1 in combination with docetaxel and oxaliplatin in patients with advanced gastro-esophageal adenocarcinoma: two parallel phase 1/2a studies.
abstract: Docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) is one of several standard chemotherapy regimens for patients with advanced gastro-esophageal adenocarcinoma (aGEA) in Europe. To enable outpatient treatment, we evaluated the maximum tolerated dose (MTD), recommended dose (RD), dose limiting toxicity (DLT) and safety of docetaxel in combination with oxaliplatin (O) and S-1 (DOS) in Caucasian patients with aGEA.
  
  
  
  We present final results of two parallel phase 1/2a studies (3 + 3 design). Escalating doses of docetaxel and S-1 with fixed dose O were given for 18 weeks every second week (DOS2w) or every third week (DOS3w) followed by S-1 maintenance therapy.
  
  
  
  Thirty-four patients (18 in DOS2w and 16 in DOS3w) were enrolled between October 2013 and June 2015. Median age was 65 years (range 49-78). DLT was most often febrile neutropenia. Most common severe non-hematological adverse events were diarrhea (9%) and fatigue (6%). The RD of DOS3w was: docetaxel 50 mg/m2, O 100 mg/m2and S-1 25 mg/m2twice daily and of DOS2w was: docetaxel 40 mg/m2, O 70 mg/m2and S-1 35 mg/m2twice daily. Overall, response rate was 56%; median progression-free survival was 9.1 months; and median overall survival was 13.2 months in 34 patients.
  
  
  
  At the RD, DOS2w and DOS3w showed an acceptable safety profile in patients with aGEA. Clinical trials ID: NCT-01928524 and EudraCT 2012-005187-10.
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.|b Institute of Clinical Research, University of Southern Denmark , Odense , Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Qvortrup
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Krogh
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Schoennemann
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.
authors.forename: Lene W
authors.initials: LW
authors.lastname: Vestermark
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.
authors.forename: Helle A
authors.initials: HA
authors.lastname: Jensen
authors.affiliation: a Department of Oncology , Odense University Hospital , Odense , Denmark.
authors.forename: Jon K
authors.initials: JK
authors.lastname: Bjerregaard
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid