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

• Published in: Cancer chemotherapy and pharmacology Vol. 74; no. 1; pp. 131 - 139
• Main Authors: Roxburgh, Patricia, Lumsden, Graeme R., Paul, James, Harden, Sharon, Sweeting, Lorna, James, Allan, Crellin, Adrian, Morrison, Rosemary, Evans, T. R. Jeffry, McDonald, Alexander C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2014; Springer; Springer Nature B.V
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - drug therapy; Adenocarcinoma - radiotherapy; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - pharmacokinetics; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Biological and medical sciences; Cancer Research; Capecitabine; Chemoradiotherapy - adverse effects; Cohort Studies; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacokinetics; Deoxycytidine - therapeutic use; Diarrhea - chemically induced; Diarrhea - etiology; Diarrhea - physiopathology; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Fatigue - chemically induced; Fatigue - etiology; Fatigue - physiopathology; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - analogs & derivatives; Fluorouracil - pharmacokinetics; Fluorouracil - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Half-Life; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nausea - chemically induced; Nausea - etiology; Nausea - physiopathology; Oncology; Original Article; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - radiotherapy; Pharmacology. Drug treatments; Pharmacology/Toxicology; Prodrugs - administration & dosage; Prodrugs - adverse effects; Prodrugs - pharmacokinetics; Prodrugs - therapeutic use; Severity of Illness Index; Survival Analysis; Tumors; Radiotherapy; Pharmacokinetics; Capecitabine; Pancreatic cancer; Locally advanced; Antineoplastic agent; Human; Drug combination; Fluoropyrimidine derivatives; Malignant tumor; Prodrug; Pancreas cancer; Digestive diseases; Combined treatment; Locally advanced stage; Pyrimidine nucleoside; Cancer; Pancreatic disease
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-014-2470-4

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.