title: Phase I study of 3-weekly docetaxel, capecitabine and oxaliplatin combination chemotherapy in patients with previously untreated advanced gastric cancer.
abstract: OBJECTIVE
  Adding docetaxel to cisplatin and 5-fluorouracil (5-FU) (DCF) significantly improved clinical efficacy in advanced gastric cancer (AGC). To further improve the efficacy and tolerability, we substituted oxaliplatin for cisplatin and capecitabine for 5-FU in the DCF regimen and performed a phase I study to determine the recommended dose (RD) and dose-limiting toxicity (DLT) of docetaxel, capecitabine and oxaliplatin (DXO) combination in patients with AGC.
  
  
  METHODS
  Previously untreated patients with histologically proven metastatic AGC and ECOG performance status 0-2 were enrolled. Docetaxel and oxaliplatin were administered i.v. on day 1. Capecitabine was administered orally bid on days 1-14. Each cycle was repeated every 3 weeks. DLTs were evaluated during the first two cycles of treatment.
  
  
  RESULTS
  Twenty-one patients were enrolled: 15 patients in dose-escalation phase and 6 patients in the extension at the RD. Median age was 50 years (range 21-65 years). At dose level 3 (60 mg/m(2) docetaxel, 1,000 mg/m(2) capecitabine, 100 mg/m(2) oxaliplatin), 1 diarrhea (DLT) was found among 6 patients while at dose level 4 (60 mg/m(2) docetaxel, 800 mg/m(2) capecitabine, 130 mg/m(2) oxaliplatin), 2 DLTs (febrile neutropenia and diarrhea) were observed among 3 patients. Therefore, the dose level 3 was determined as RD. DLTs include grade 3 diarrhea and febrile neutropenia. Cumulative (all cycles) grade 3/4 toxicity included neutropenia (75%), leucopenia (50%), febrile neutropenia (25%), diarrhea (17%), and neuropathy (17%). Of 14 patients with measurable lesions, 11 achieved partial response and 3 showed stable disease.
  
  
  CONCLUSIONS
  The RD of the DXO regimen in patients with AGC is capecitabine 1,000 mg/m(2) twice daily on days 1-14, in combination with docetaxel 60 mg/m(2) (day 1) and oxaliplatin 100 mg/m(2) (day 1) repeated every 3 weeks. The DXO regimen seems to have promising activity and offers an easy alternative to DCF. The toxicities appear to be still substantial, but manageable.
authors: Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2 Dong, Songpa Gu, Seoul, 138-736, Korea.
authors: Sun Jin
authors: SJ
authors: Sym
authors: Min-Hee
authors: MH
authors: Ryu
authors: Hye Jin
authors: HJ
authors: Kang
authors: Sung Sook
authors: SS
authors: Lee
authors: Heung-Moon
authors: HM
authors: Chang
authors: Jae Lyun
authors: JL
authors: Lee
authors: Tae Won
authors: TW
authors: Kim
authors: Jeong Hwan
authors: JH
authors: Yook
authors: Sung Tae
authors: ST
authors: Oh
authors: Byung Sik
authors: BS
authors: Kim
authors: Yoon-Koo
authors: YK
authors: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil