Annals of Oncology Advance Access originally published online on June 4, 2008
Annals of Oncology 2008 19(10):1742-1748; doi:10.1093/annonc/mdn375
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gastrointestinal tumors |
Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies
1 Division of Medical Oncology, Washington University School of Medicine, St Louis
2 Center for Hematology/Oncology, Boynton Beach
3 Division of Molecular Oncology
4 Division of Biostatistics, Washington University School of Medicine, St Louis
5 Division of Hematology/Oncology, University of Virginia, Charlottesville
6 UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, USA
* Correspondence to: Dr B. R. Tan, Washington University School of Medicine, 660 South Euclid Avenue, Box 8056, St Louis, MO 63110, USA. Tel: +314-362-5737; Fax: +314-362-7086; E-mail: btan{at}im.wustl.edu
Background: Oxaliplatin, gemcitabine and capecitabine are all active agents against upper gastrointestinal and pancreaticobiliary cancers.
Patients and methods: Patients with upper gastrointestinal malignancies treated with 0–2 prior chemotherapy regimens received oxaliplatin (85–100 mg/m2) as a 2-h i.v. infusion with gemcitabine (800–1000 mg/m2) at a constant rate i.v. infusion (CI) of 10 mg/m2/min on days 1 and 15 of a 28-day cycle. Capecitabine (600–800 mg/m2) was administered orally twice a day on days 1–7 and 15–21. A three per cohort dose escalation schema was used to determine the maximum tolerated dose (MTD) and the dose-limiting toxic effects (DLTs) of this combination regimen.
Results: Thirty patients with advanced upper gastrointestinal malignancies were enrolled. The MTD was defined as oxaliplatin 100 mg/m2 i.v. over 2 h plus gemcitabine 800 mg/m2 i.v. at a CI of 10 mg/m2/min on days 1 and 15 with capecitabine 800 mg/m2 p.o. b.i.d. days 1–7 and 15–21 of a 29-day cycle. DLTs include grade 3 fatigue and grade 3 dyspnea. One complete and two partial responses were observed.
Conclusions: This biweekly schedule of oxaliplatin, gemcitabine and capecitabine is tolerable and warrants further investigation in biliary and pancreatic malignancies.
Key words: Capecitabine, gemcitabine, oxaliplatin, upper gastrointestinal malignancies
Received for publication April 1, 2008. Revision received May 1, 2008. Accepted for publication May 2, 2008.