title: A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer.
abstract: OBJECTIVE
  The purpose of this phase I study was to determine the safety, toxicity, maximum tolerated dose, and pharmacokinetics of capecitabine when administered concurrently with radiotherapy in patients with localised, inoperable pancreatic adenocarcinoma.
  
  
  METHODS
  Eligible patients, with adequate performance status and organ function, were treated in escalating dose cohorts with capecitabine, administered 7 days a week, twice daily, and radiotherapy (50.4 Gy in 28 fractions over 38 days). Cohorts of six patients were treated at four planned dose levels. Pharmacokinetic (PK) studies were undertaken on day 1 of treatment.
  
  
  RESULTS
  Twenty-five patients, performance status ECOG ≤2, were recruited to the study. Dose-limiting toxicities were grade 3 vomiting (1 patient) and grade 3 fatigue (1 patient), both at 1,000 mg/m². The recommended phase II dose was 825 mg/m². No grade 3/4 haematological toxicities were observed. PK studies did not suggest any effect of pancreatic malignancy or concurrent radiotherapy on the PK parameters of capecitabine and its metabolites.
  
  
  CONCLUSIONS
  Capecitabine-based chemo-radiotherapy, using a twice daily dosing schedule of 825 mg/m² given 7 days per week concurrently with 50.4 Gy external beam radiotherapy, is well tolerated in patients with locally advanced pancreatic cancer.
authors.affiliation: Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow, G12 OYN, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Roxburgh
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Lumsden
authors.forename: James
authors.initials: J
authors.lastname: Paul
authors.forename: Sharon
authors.initials: S
authors.lastname: Harden
authors.forename: Lorna
authors.initials: L
authors.lastname: Sweeting
authors.forename: Allan
authors.initials: A
authors.lastname: James
authors.forename: Adrian
authors.initials: A
authors.lastname: Crellin
authors.forename: Rosemary
authors.initials: R
authors.lastname: Morrison
authors.forename: T R Jeffry
authors.initials: TR
authors.lastname: Evans
authors.forename: Alexander C
authors.initials: AC
authors.lastname: McDonald
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000009:adverse effects*; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005221:Fatigue / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil