5-FU split dose; a phase I/II and pharmacokinetic study of a different schedule of the Nordic regimen in advanced colorectal carcinoma.

Abstract:

PURPOSE:Despite more than four decades of fluoro-pyrimidine treatment in different cancers, the optimal schedule is still not known. The plasma half-life of 5-fluorouracil (5-FU) is extremely short and continuous infusion has gained popularity. In this study we explored whether repeated bolus 5-FU injections could improve the results. PATIENTS AND METHODS:Forty-three patients with advanced gastrointestinal carcinoma, where no standard treatment was available, were included in the phase I study. The initial dose of 5-FU was 250 mg/m2 with 30 mg/m2 leucovorin, repeated three hours later. Treatments were repeated every week. Twenty-six patients were recruited in the following phase II after maximal-tolerated dose (MTD) was reached. Plasma was collected for 5-FU pharmacokinetics. RESULTS:Diarrhoea was the dose-limiting toxicity (DLT), and was reached at 450 mg/m2. One complete and three partial responses (24%) were seen in the phase II study at 400 mg/m2. In addition, several patients had lasting subjective improvements. The treatments were well-tolerated but accumulated toxicity was seen after several months. Dose intensity was 89% after four months of treatment. A great interpatient variability was seen in 5-FU pharmacokinetics. The plasma AUC correlated with the 5-FU dose and toxicity, but not with the tumour response. CONCLUSION:A split of the 5-FU push bolus injection is possible with maintained treatment activity and surprisingly high doses can be tolerated; a weekly dose intensity of 800 mg/m2 could be reached compared with 500 mg/m2 in the standard Nordic FLv schedule.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Berglund A,Carlsson G,Gustavsson B,Frödin JE,Ragnhammar P,Glimelius B

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

1789-94

issue

2C

eissn

0250-7005

issn

1791-7530

journal_volume

23

pub_type

临床试验,杂志文章
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    authors: Häufel T,Dormann S,Hanusch J,Schwieger A,Bauer G

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    authors: Hillbertz NS,Hirsch JM,Jalouli J,Jalouli MM,Sand L

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    authors: Saito K,Iwashita J,Murata J,Abe T

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    doi:

    authors: Gabius S,Joshi SS,Gabius HJ,Sharp JG

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  • Weekly paclitaxel in combination with doxifluridine for peritoneally disseminated gastric cancer with malignant ascites.

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    journal_title:Anticancer research

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    doi:

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  • Antineoplastic activity of zoledronic acid and denosumab.

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    doi:

    authors: Coradini D,Biffi A,Pirronello E,Di Fronzo G

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    doi:

    authors: Slominski A,Costantino R,Howe J,Moellmann G

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    doi:10.21873/anticanres.13451

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    pub_type: 临床试验,杂志文章

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    authors: Siggelkow W,Zimny M,Faridi A,Petzold K,Buell U,Rath W

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    pub_type: 临床试验,杂志文章

    doi:

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    doi:

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  • Thymidylate synthase levels in tumor biopsies from patients with colorectal cancer.

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    pub_type: 临床试验,杂志文章

    doi:

    authors: Mulder NH,Timmer-Bosscha H,Meersma GJ,Verschueren RC

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    journal_title:Anticancer research

    pub_type: 杂志文章

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    pub_type: 杂志文章

    doi:

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    journal_title:Anticancer research

    pub_type: 杂志文章,收录出版

    doi:

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  • Pentafecta Outcomes of 230 Cases of Robotic-assisted Radical Prostatectomy with Bilateral Neurovascular Bundle Preservation.

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    doi:

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    doi:

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