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A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer.

Cheeseman SL, Joel SP, Chester JD, Wilson G, Dent JT, Richards FJ, Seymour MT - Br. J. Cancer (2002)

Bottom Line: Fluorouracil pharmacokinetics during MdG were compared with dG.With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths.MdG and OxMdG are convenient and well-tolerated.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK Clinical Centre in Leeds, Cookridge Hospital, Leeds LS16 6QB, UK.

ABSTRACT
The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified 'Modified de Gramont' (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m(-2)), then ambulatory 46-h fluorouracil infusion (2000-3600 mg m(-2), cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m(-2). Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m(-2) bolus + 2800 mg m(-2) 46-h infusion. A lower dose of 400 mg m(-2) bolus + 2400 mg m(-2) infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC(0-48 h)) at this lower dose is equivalent to dG. With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial.

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dG, MdG and OxMdG. Plasma FU levels are shown for nine patients receiving dG (day 2 data extrapolated from day 1) and in 10 receiving MdG, at the lower dose of 400 mg m−2 bolus+2400 mg m−2 46 h infusion as used in the OxMdG schedule.
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fig1: dG, MdG and OxMdG. Plasma FU levels are shown for nine patients receiving dG (day 2 data extrapolated from day 1) and in 10 receiving MdG, at the lower dose of 400 mg m−2 bolus+2400 mg m−2 46 h infusion as used in the OxMdG schedule.

Mentions: MdG comprised: fixed dose d,l-LV 350 mg (or l-LV, 175 mg) as a 2-h i.v. infusion; then FU i.v. bolus over 5 min; then 46-h FU infusion (see Figure 1Figure 1


A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer.

Cheeseman SL, Joel SP, Chester JD, Wilson G, Dent JT, Richards FJ, Seymour MT - Br. J. Cancer (2002)

dG, MdG and OxMdG. Plasma FU levels are shown for nine patients receiving dG (day 2 data extrapolated from day 1) and in 10 receiving MdG, at the lower dose of 400 mg m−2 bolus+2400 mg m−2 46 h infusion as used in the OxMdG schedule.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376131&req=5

fig1: dG, MdG and OxMdG. Plasma FU levels are shown for nine patients receiving dG (day 2 data extrapolated from day 1) and in 10 receiving MdG, at the lower dose of 400 mg m−2 bolus+2400 mg m−2 46 h infusion as used in the OxMdG schedule.
Mentions: MdG comprised: fixed dose d,l-LV 350 mg (or l-LV, 175 mg) as a 2-h i.v. infusion; then FU i.v. bolus over 5 min; then 46-h FU infusion (see Figure 1Figure 1

Bottom Line: Fluorouracil pharmacokinetics during MdG were compared with dG.With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths.MdG and OxMdG are convenient and well-tolerated.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK Clinical Centre in Leeds, Cookridge Hospital, Leeds LS16 6QB, UK.

ABSTRACT
The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified 'Modified de Gramont' (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m(-2)), then ambulatory 46-h fluorouracil infusion (2000-3600 mg m(-2), cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m(-2). Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m(-2) bolus + 2800 mg m(-2) 46-h infusion. A lower dose of 400 mg m(-2) bolus + 2400 mg m(-2) infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC(0-48 h)) at this lower dose is equivalent to dG. With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial.

Show MeSH
Related in: MedlinePlus