title: A phase I study of S-1 in combination with nab-paclitaxel in patients with unresectable or recurrent gastric cancer.
abstract: BACKGROUND
  In Japan, S-1, an oral fluoropyrimidine, plus cisplatin is a standard regimen for advanced gastric cancer, whereas nab-paclitaxel is a treatment option. We aimed to evaluate the tolerance, pharmacokinetics, safety, and clinical efficacy of S-1 combined with nab-paclitaxel in patients with advanced gastric cancer in a phase 1 study.
  
  
  METHODS
  The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus nab-paclitaxel. The study was designed in accordance with a standard 3 + 3 method. Patients received 3-week cycles of treatment. S-1 was administered orally at 80 mg/m2twice daily for 14 days, and nab-paclitaxel was administered as an intravenous infusion at 180, 220, or 260 mg/m2on day 1 or 8.
  
  
  RESULTS
  Among the 16 patients enrolled, dose-limiting toxicity was observed in one patient at level 2a (S-1 80 mg/m2twice daily plus nab-paclitaxel 220 mg/m2on day 1). The MTD was not obtained, but the RD was established as level 3a (S-1 80 mg/m2twice daily plus nab-paclitaxel 260 mg/m2on day 1). The most common grade 3-4 toxicity was neutropenia (62.5 %). The overall response rate was 54.5 %. The pharmacokinetic profiles of coadministered S-1 and paclitaxel were comparable to those of nab-paclitaxel or S-1 alone.
  
  
  CONCLUSIONS
  Based on the present results, the RD was determined as level 3a (S-1 80 mg/m2twice daily plus nab-paclitaxel 260 mg/m2on day 1). This combination therapy was well tolerated and showed antitumor efficacy in patients with advanced gastric cancer.
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan. norisuke@kcch.jp.
authors.forename: Norisuke
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishido
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Keisho
authors.initials: K
authors.lastname: Chin
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsusaka
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inokuchi
authors.affiliation: Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kumekawa
authors.affiliation: Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
mesh_terms: D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel
keywords: Gastric cancer; Nab-paclitaxel; S-1