Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: A randomised crossover trial in advanced colorectal cancer

M. M. Borner, P. Schöffski, R. De Wit, F. Caponigro, G. Comella, A. Sulkes, G. Greim, G. J. Peters, K. Van der Born, J. Wanders, R. F. De Boer, C. Martin, P. Fumoleau

Research output: Contribution to journalArticle

Abstract

The aim of this study was to determine the patient's preference for oral UFT/leucovorin (LV) or intravenous (i.v.) 5-fluorouracil (5-FU)/LV chemotherapy in metastatic colorectal cancer and to compare 5-FU exposure with these two treatment options. A total of 37 previously untreated patients with advanced colorectal cancer were randomised to start treatment with either oral UFT 300 mg/m2/day plus oral LV 90 mg/day for 28 days every 5 weeks or i.v. 5-FU 425 mg/m2/day plus LV 20 mg/m2/day for 5 days every 4 weeks. For the second treatment cycle, patients were crossed-over to the alternative treatment regimen. Prior to the first and after the second therapy cycle, patients were required to complete a therapy preference questionnaire (TPQ). The pharmacokinetics of 5-FU were determined by taking blood samples on days 8, 15 or 22 and 28 for UFT and on days 1 and 5 for i.v. 5-FU. 36 patients were eligible. 84% of the patients preferred oral UFT over i.v. 5-FU. After having experienced both treatment modalities, patients indicated taking the medication at home, less stomatitis and diarrhoea, and pill over injection as the most important reasons for their preference. The area under the plasma concentration curve (AUC) for 5-FU after UFT administration was 113 μM×min on day 8, 114 on day 15 and 98 on day 28; the peak levels (Cmax) were 1.2, 1.3 and 1.0 μM, respectively. The AUC for the 5-FU/LV courses was 3083 μM×min for day 1 and 3809 for day 5 (P=0.002). The Cmax was 170.1 and 196.2 μM (P=0.06) and the clearance 2.6 and 1.9 l/min, respectively (P=0.002). Patients with metastatic colorectal cancer clearly preferred oral over i.v. chemotherapy treatment. This choice was most importantly influenced by convenience and toxicity considerations. Although i.v. bolus 5-FU leads to higher peak 5-FU concentrations and AUC values compared with oral UFT, this pharmacokinetic advantage of i.v. 5-FU seems to translate mainly into higher toxicity as seen in large randomised studies comparing oral UFT/LV with i.v. 5-FU/LV. Oral UFT/LV compares favourably with i.v. 5-FU/LV in terms of toxicity and patient's preference and leads to prolonged 5-FU exposure, which is comparable to continuous i.v. 5-FU treatment.

Original languageEnglish
Pages (from-to)349-358
Number of pages10
JournalEuropean Journal of Cancer
Volume38
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Leucovorin
Patient Preference
Fluorouracil
Cross-Over Studies
Colorectal Neoplasms
Pharmacokinetics
Area Under Curve
Therapeutics
Drug Therapy
Stomatitis

Keywords

  • 5-Fluorouracil
  • Leucovorin
  • Oral
  • Patient's preference
  • Pharmacokinetics
  • Randomised crossover trial
  • UFT

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin : A randomised crossover trial in advanced colorectal cancer. / Borner, M. M.; Schöffski, P.; De Wit, R.; Caponigro, F.; Comella, G.; Sulkes, A.; Greim, G.; Peters, G. J.; Van der Born, K.; Wanders, J.; De Boer, R. F.; Martin, C.; Fumoleau, P.

In: European Journal of Cancer, Vol. 38, No. 3, 2002, p. 349-358.

Research output: Contribution to journalArticle

Borner, MM, Schöffski, P, De Wit, R, Caponigro, F, Comella, G, Sulkes, A, Greim, G, Peters, GJ, Van der Born, K, Wanders, J, De Boer, RF, Martin, C & Fumoleau, P 2002, 'Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: A randomised crossover trial in advanced colorectal cancer', European Journal of Cancer, vol. 38, no. 3, pp. 349-358. https://doi.org/10.1016/S0959-8049(01)00371-9
Borner, M. M. ; Schöffski, P. ; De Wit, R. ; Caponigro, F. ; Comella, G. ; Sulkes, A. ; Greim, G. ; Peters, G. J. ; Van der Born, K. ; Wanders, J. ; De Boer, R. F. ; Martin, C. ; Fumoleau, P. / Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin : A randomised crossover trial in advanced colorectal cancer. In: European Journal of Cancer. 2002 ; Vol. 38, No. 3. pp. 349-358.
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AU - De Wit, R.

AU - Caponigro, F.

AU - Comella, G.

AU - Sulkes, A.

AU - Greim, G.

AU - Peters, G. J.

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N2 - The aim of this study was to determine the patient's preference for oral UFT/leucovorin (LV) or intravenous (i.v.) 5-fluorouracil (5-FU)/LV chemotherapy in metastatic colorectal cancer and to compare 5-FU exposure with these two treatment options. A total of 37 previously untreated patients with advanced colorectal cancer were randomised to start treatment with either oral UFT 300 mg/m2/day plus oral LV 90 mg/day for 28 days every 5 weeks or i.v. 5-FU 425 mg/m2/day plus LV 20 mg/m2/day for 5 days every 4 weeks. For the second treatment cycle, patients were crossed-over to the alternative treatment regimen. Prior to the first and after the second therapy cycle, patients were required to complete a therapy preference questionnaire (TPQ). The pharmacokinetics of 5-FU were determined by taking blood samples on days 8, 15 or 22 and 28 for UFT and on days 1 and 5 for i.v. 5-FU. 36 patients were eligible. 84% of the patients preferred oral UFT over i.v. 5-FU. After having experienced both treatment modalities, patients indicated taking the medication at home, less stomatitis and diarrhoea, and pill over injection as the most important reasons for their preference. The area under the plasma concentration curve (AUC) for 5-FU after UFT administration was 113 μM×min on day 8, 114 on day 15 and 98 on day 28; the peak levels (Cmax) were 1.2, 1.3 and 1.0 μM, respectively. The AUC for the 5-FU/LV courses was 3083 μM×min for day 1 and 3809 for day 5 (P=0.002). The Cmax was 170.1 and 196.2 μM (P=0.06) and the clearance 2.6 and 1.9 l/min, respectively (P=0.002). Patients with metastatic colorectal cancer clearly preferred oral over i.v. chemotherapy treatment. This choice was most importantly influenced by convenience and toxicity considerations. Although i.v. bolus 5-FU leads to higher peak 5-FU concentrations and AUC values compared with oral UFT, this pharmacokinetic advantage of i.v. 5-FU seems to translate mainly into higher toxicity as seen in large randomised studies comparing oral UFT/LV with i.v. 5-FU/LV. Oral UFT/LV compares favourably with i.v. 5-FU/LV in terms of toxicity and patient's preference and leads to prolonged 5-FU exposure, which is comparable to continuous i.v. 5-FU treatment.

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