title: Phase II study of capecitabine and cisplatin in previously untreated advanced biliary tract cancer.
abstract: BACKGROUND
  Biliary tract cancer is one of the most aggressive and chemotherapy-refractory tumors. Although only curative treatment modality is surgery, most patients are not suitable for surgery due to advanced stage of the disease at diagnosis. Thus most patients with biliary tract cancer are possible candidates for palliative chemotherapy. The standard chemotherapeutic regimen is still to be defined, however. We performed a phase II study of combination chemotherapy with capecitabine and cisplatin in these patients to evaluate efficacy and toxicity of the regimen.
  
  
  METHODS
  Patients with previously untreated metastatic, recurrent, or inoperable biliary tract cancer were enrolled. Eligible patients were screened as following: (1) histologically confirmed, (2) age between 18 and 75 years, (3) at least one measurable lesion according to RECIST criteria, (4) ECOG performance status <or=2, (5) a life expectancy of at least 3 months, and (6) adequate laboratory values. Patients received capecitabine (2,500 mg/m2/day, days 1 to 14) and cisplatin (60 mg/m2, day 1) every 3 weeks. Response was assessed for every two cycles of chemotherapy and treatment was stopped when tumor had progressed or stable with no further response.
  
  
  RESULTS
  Thirty-two patients were enrolled, 20 (62.5%) were male and 12 (37.5%) were female and the median age was 54 years (33-71 years). Fifteen patients (46.9%) had gallbladder cancer, 13 (40.6%) had intrahepatic cholangiocarcinoma, and 4 (12.5%) had extrahepatic biliary cancer. The most frequent metastatic sites were lymph nodes (20/32, 62.5%) and liver (28/32, 56.3%). No complete response was observed and partial response was observed in 13/32 patients. By the intent-to-treat analysis, the overall response rate was 40.6% (95% CI, 23.7-59.4) with 0 CR and 13 PRs. Stable disease was observed in 3 patients (9.4%), and 11 patients (34.4%) had progressive disease. The median time to progression was 3.5 months (95% CI, 1.3-5.8), and the median overall survival was 12.4 months (95% CI, 6.3-18.5) after the median follow-up duration of 9.5 months (4.8-26.1 months). A total of 108 cycles of chemotherapy was delivered. Grade 3 hematologic toxicities included neutropenia (5, 15.6%), anemia (1, 3.1%), and thrombocytopenia (1, 3.1%) per patient, and no grade 4 hematologic toxicities were observed. Grade 3 non-hematologic toxicities included hyperbilirubinemia (2, 6.3%), increase of alkaline phosphatase (2, 6.3%), hand-foot syndrome (2, 6.3%), anorexia, and diarrhea (1, 3.1%) per patient, respectively. There was no treatment-related death.
  
  
  CONCLUSIONS
  The combination chemotherapy of capecitabine and cisplatin demonstrated a promising antitumor activity with mild toxicity profile in patients with advanced biliary tract cancer.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, South Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Lee
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Hwang
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Heo
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil