Trimetrexate as biochemical modulator of 5-fluorouracil/leucovorin in advanced colorectal cancer: final results of a randomised European study.
| Autor: | Punt CJ; University Medical Centre, St. Radboud, Nijmegen, The Netherlands. c.punt@onco.azn.nl, Keizer HJ, Douma J, Skovsgaard T, Schüller J, Muller EW, Ten Napel CH, Croles JJ, Lochs H, Zhang J, Hammershaimb L |
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| Jazyk: | angličtina |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2002 Jan; Vol. 13 (1), pp. 81-6. |
| DOI: | 10.1093/annonc/mdf045 |
| Abstrakt: | Background: Trimetrexate (TMTX) is a biochemical modulator of 5-fluorouracil (5-FU) and leucovorin (LV). Phase II trials have shown promising activity of 5-FU/LV/TMTX in patients with advanced colorectal cancer (ACC). This trial evaluated the effect of TMTX in combination with 5-FU/LV as first-line treatment in ACC. Patients and Methods: Patients with ACC were randomised to receive either intravenous LV 200 mg/m2/5-FU 600 mg/m2 or TMTX 110 mg/m2 followed 24 h later by LV 200 mg/m2/5-FU 500 mg/m2 plus oral LV rescue. Both schedules were given weekly for 6 weeks every 8 weeks. Patients were evaluated for progression-free survival (PFS), overall survival (OS), tumour response, quality of life (QoL) and toxicity. Results: A total of 365 patients were randomised. A statistically significant prolongation of median PFS was seen in patients treated with TMTX/5-FU/LV compared with 5-FU/LV (5.4 months versus 4.1 months, respectively; P = 0.03), and a trend towards a significant benefit for OS (13.4 months versus 10.5 months, respectively; P = 0.08). Tumour response, QoL and toxicity were comparable between the two arms. Diarrhoea was the most frequently occurring grade 3 or 4 toxicity (22% and 30%, respectively). Conclusions: The addition of TMTX to a weekly regimen of 5-FU/LV results in a small but significant improvement in PFS without adding toxicity or worsening QoL in patients with ACC. |
| Databáze: | MEDLINE |
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