1. ¹Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
2. ²Discipline of Gastrointestinal Surgery, University of Sao Paulo, Sao Paulo, Brazil
3. ³Hospital Sirio Libanes, Sao Paulo, Brazil
4. ⁴Department of Oncology, Royal Victoria Hospital, Montreal, Quebec, Canada
5. ⁵Louisiana Oncology Associates, Lafayette, Louisiana 70506, USA
6. ⁶Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA

Correspondence: Dr PM Hoff, Centro de Oncologia do Hospital Sirio Libanes, Rua Adma Jafet 91, Sao Paulo 01308-050, Brazil. E-mail: hoffpaulo@yahoo.com

Received 13 October 2005; Revised 24 June 2008; Accepted 30 June 2008; Published online 12 August 2008.

Abstract

Prolonged infusions have been shown to be safer and potentially more effective than bolus regimens of 5-fluorouracil (5-FU) as treatment for metastatic colorectal cancer (mCRC). However, infusional 5-FU requires central venous access and costly infusion pumps. Oral fluoropyrimidines enable longer exposures to 5-FU with increased convenience. Tegafur–uracil (UFT) with leucovorin (LV) given thrice daily has improved safety plus comparable survival and response rates to bolus 5-FU/LV. We conducted a phase II clinical study in 98 patients with mCRC to evaluate if UFT with LV given twice daily provided comparable time to progression (TTP), efficacy and tolerability to that reported for thrice daily in two phase III clinical studies. Secondary objectives included overall response rate (ORR) and overall survival (OS). Median TTP was 3.8 months, when compared with 3.5 months for thrice daily. The ORR (11%) and median OS (12.8 months) with twice daily administration were similar to that of thrice daily administration (12% and 12.4 months). The incidence of grade 3/4 treatment-related diarrhoea was 30% on the twice daily and 21% on the thrice daily schedule. These results suggest that twice daily administration has similar efficacy and tolerability to thrice daily administration and is an acceptable alternative for patients who would benefit from UFT with LV therapy.