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

Roxburgh, P. , Lumsden, G. R., Paul, J. , Harden, S., Sweeting, L., James, A., Crellin, A., Morrison, R., Evans, T. R. J. and McDonald, A. C. (2014) A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer. Cancer Chemotherapy and Pharmacology, 74(1), pp. 131-139. (doi: 10.1007/s00280-014-2470-4) (PMID:24819683)

Abstract

Purpose<p></p> 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.<p></p> Methods<p></p> 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.<p></p> Results<p></p> 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.<p></p> Conclusion<p></p> 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Harden, Ms Sharon and Sweeting, Miss Lorna and Paul, Mr James and Morrison, Mrs Rosemary and Evans, Professor Jeff and Roxburgh, Dr Patricia
• Authors: Roxburgh, P., Lumsden, G. R., Paul, J., Harden, S., Sweeting, L., James, A., Crellin, A., Morrison, R., Evans, T. R. J., and McDonald, A. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer Chemotherapy and Pharmacology
• Publisher: Springer-Verlag
• ISSN: 0344-5704
• ISSN (Online): 1432-0843