title: A phase I/II study of combination chemotherapy with gemcitabine and 5-fluorouracil for advanced pancreatic cancer.
abstract: BACKGROUND
  In an effort to improve efficacy of single-agent gemcitabine in pancreatic cancer, several studies have examined the effects of 5-FU combined with gemcitabine. However, no studies to date have been performed in Japanese patients. We thus conducted a phase I/II study of gemcitabine and infusional 5-FU in Japanese patients to determine a recommended dosage for this combination and clarify efficacy and toxicity.
  
  
  METHODS
  Phase I evaluated the frequency of dose limiting toxicity of two 5-FU dosages (400 and 500 mg/m(2)/day) infused continuously over 5 days combined with gemcitabine 1000 mg/m(2) x 3 every 4 weeks. Results from phase I determined the recommended dosage to be examined in phase II for effect on survival period, clinical benefit response (CBR), tumor response and safety.
  
  
  RESULTS
  A total of 34 chemo-naive patients were entered into the study. All had a Karnofsky performance of > or =50 points and distant metastases. Dose limiting toxicities in phase I determined the recommended 5-FU dosage at 400 mg/m(2)/day. Grade 3-4 hematological toxicities (neutropenia, leukopenia and thrombocytopenia) were the most common severe toxicities. For the 28 patients administered the recommended dosage, 1-year survival rate was 14.3%, median survival time 7.1 months and progression free survival 3.2 months. Seven patients achieved a 25% overall response rate and three showed 27.3% improvement in CBR.
  
  
  CONCLUSIONS
  Although a meaningful survival benefit over single-agent gemcitabine was not demonstrated, 5-FU 400 mg/m(2)/day infused continuously over 5 days in combination with gemcitabine 1000 mg/m(2) x 3 every 4 weeks appeared to be a moderately effective palliative treatment with low toxicity in Japanese patients with metastatic pancreatic cancer.
authors.affiliation: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, 104-0045, Japan. tokusaka@ncc.go.jp
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Akihiro
authors.initials: A
authors.lastname: Funakoshi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sumii
mesh_terms: D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine