A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer

Purpose 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/m 2 . The recommended phase II dose was 825 mg/m 2 . 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. Conclusion Capecitabine-based chemo-radiotherapy, using a twice daily dosing schedule of 825 mg/m 2 given 7 days per week concurrently with 50.4 Gy external beam radiotherapy, is well tolerated in patients with locally advanced pancreatic cancer.