Phase I study of 3-weekly docetaxel, capecitabine and oxaliplatin combination chemotherapy in patients with previously untreated advanced gastric cancer.
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.
Sym
Sun Jin
SJ
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.
Ryu
Min-Hee
MH
Kang
Hye Jin
HJ
Lee
Sung Sook
SS
Chang
Heung-Moon
HM
Lee
Jae Lyun
JL
Kim
Tae Won
TW
Yook
Jeong Hwan
JH
Oh
Sung Tae
ST
Kim
Byung Sik
BS
Kang
Yoon-Koo
YK
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
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