Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study.

Gramont, Aimery de; Bosset, J.-F.; Milan, Chantal; Rougier, Philippe; Bouché, Olivier; Étienne, Pierre; Morvan, F.; Louvet, Christophe; Guillot, T.; François, Ετιεννε; Bedenne, Laurent

doi:10.1200/jco.1997.15.2.808

Cited by 828 publications

(351 citation statements)

References 21 publications

Supporting

Mentioning

327

Contrasting

Unclassified

Order By: Relevance

“…The optimum fluoropyrimidine therapy may continue to be debated, but de Gramont's LV5FU2 regimen (dG) is a strong contender, with a good track record of efficacy and low toxicity in large phase III randomised trials (de Gramont et al, 1997;Douillard et al, 2000;Maughan et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…It involves a 2-h infusion of LV (200 mg m 72 ), bolus injection of FU (400 mg m 72 ), then 22-h infusion of FU (600 mg m 72 ), with the same sequence repeated on the second day, repeated fortnightly (de Gramont et al, 1988). It was compared with the Mayo Clinic 5-day bolus FU/LV regimen in a 448-patient randomised trial, and showed a better response rate (32.6% vs 14.4%; P=0.0004), and median progression-free survival (27.6 vs 22 weeks; P50.0012) with significantly reduced rates of diarrhoea, mucositis and neutropenia; however, overall survival was not significantly improved (de Gramont et al, 1997). Following this trial dG was adopted as a standard therapy option by many oncologists, especially in France and the UK.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2002

View full text Add to dashboard Cite

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 72 ), then ambulatory 46-h fluorouracil infusion (2000 -3600 mg m 72 , cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m 72 . Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m 72 bolus + 2800 mg m 72 46-h infusion. A lower dose of 400 mg m 72 bolus + 2400 mg m 72 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 51% 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%. 1988). It was compared with the Mayo Clinic 5-day bolus FU/LV regimen in a 448-patient randomised trial, and showed a better response rate (32.6% vs 14.4%; P=0.0004), and median progression-free survival (27.6 vs 22 weeks; P50.0012) with significantly reduced rates of diarrhoea, mucositis and neutropenia; however, overall survival was not significantly improved (de Gramont et al, 1997). Following this trial dG was adopted as a standard therapy option by many oncologists, especially in France and the UK.Its low toxicity profile makes dG a good basis for combination chemotherapy. Pivotal trials of the design 'dG+new agent' have been performed in first-line therapy of metastatic colorectal cancer using oxaliplatin or irinotecan (Douillard et al, 2000), in each case producing a high response rate and good safety profile. Similar trials are now ongoing in the adjuvant setting.Although dG can be administered on an ambulatory, out-patient basis, many units find it more convenient to admit patients. This, together with the high dose of LV, and a labour-intensive administration schedule, place high demands on healthcare resources (Ross et al, 1998). Furthermore, repeated hospital visits or admissions during dG may detract from the benefits of its low toxicity profile.Along with others (see Discussion), we reasoned that it would be possible to modify the dG regimen, reducing its ...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Bimonthly infusional LV/5-FU (de Gramont regimen) has become a widely accepted treatment with a higher response rate and lower toxicity than bolus LV/5-FU (de Gramont et al, 1997). Modification of the de Gramont regimen with folinic acid and bolus 5-FU given only on the first day followed by a 46 h infusion of 5-FU has potential advantages.…”

Section: Discussionmentioning

confidence: 99%

“…The response to this drug varies depending on whether bolus or infusional chemotherapy is given. (Erlichman et al, 1988;Advanced Colorectal Cancer Meta-Analysis Project, 1992) During the last decade it has become clear that biomodulation with folinic acid (FA) and alteration of the scheduling of 5-FU can significantly improve the response rate and toxicity profile (de Gramont et al, 1997). Nevertheless, only about 20 -30% of patients respond to 5-FU based therapy (Skibber et al, 2001) and patients with metastatic disease are not cured by chemotherapy.…”

mentioning

confidence: 99%

Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer

Leonard

Seymour²,

James

et al. 2002

Br J Cancer

View full text Add to dashboard Cite

We investigated the activity of irinotecan given with a more convenient modified bimonthly de Gramont regimen of bolus and infusional 5-fluorouracil [IrMdG] in advanced or metastatic colorectal cancer in the first and second line setting. Irinotecan 180 mg m 72 was infused over 90 min. L-folinic acid 175 mg or d,l folinic acid 350 mg was given over 2 h followed by a bolus of 5-fluorouracil (400 mg m 72 ) and a 46 h continuous infusion of 5-fluorouracil (2.4 -2.8 g m 72 ). Forty-six previously untreated patients (Group A) and 36 who had received 5-fluorouracil for metastatic disease (Group B) were recruited. Seventy-eight patients were evaluable for response. A partial response was seen in 13 out of 43 (30% [95%CI 28.1 -31.9%]) in Group A and 8/35 (23% [95% CI 17.9 -28.1%]) in Group B. 40% (95%CI 38.1 -41.9%) of Group A and 26% (95% CI 20.9 -31.1%) of Group B patients achieved disease stabilisation. The median progression free survival from the start of this treatment was 7 months (95% CI 4.4 -9.6 months) in Group A and 5 months (95% CI 2.8 -7.2 months) in Group B. Median overall survival was 14 months (95% CI 9.0 -18.9) in Group A and 11 months (95% CI 5.9 -16.1) in Group B. Grade 3 -4 toxicity in both treatment groups were similar; leucopenia 17% and diarrhoea 7 -8%. Grade 3 -4 mucositis was not seen and severe alopecia affected only three patients. IrMdG is an active and well-tolerated regimen for both the first and second line treatment of advanced colorectal cancer.

show abstract

“…Furthermore, in our regimen the schedule of 5-FU given by bolus injection may not be optimal. The combination of 5-FU and LV according to de Gramont allows for the administration of higher doses of 5-FU; furthermore, the continuous infusion increases the time exposition of tumour cells to 5-FU, which may translate into a better oncolytic effect (de Gramont et al, 1997).…”

mentioning

confidence: 99%

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: A low cost effective regimen

Cascinu¹,

Baldelli²,

Catalano³

et al. 2002

Br J Cancer

View full text Add to dashboard Cite

Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m 72 i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m 72 i.v. followed by 5-fluorouracil 400 mg m 72 i.v. bolus and 600 mg m 72 i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m 72 i.v. bolus on day 2, every 6 weeks. Grades 3 -4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1 -61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.

show abstract

Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study.

Abstract: The bimonthly regimen was more effective and less toxic than the monthly regimen and definitely increased the therapeutic ratio. However, there was no evidence of increased survival.

Cited by 828 publications

References 21 publications

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

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

Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: A low cost effective regimen

Contact Info

Product

Resources

About