FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study

Tournigand, Christophe; André, Thierry; Achille, Emmanuel; Lledo, Gérard; Flesh, Michel; Méry-Mignard, D.; Quinaux, Emmanuel; Couteau, C.; Buyse, Marc; Ganem, G.; Landi, Bruno; Colin, Philippe; Louvet, Christophe; Gramont, Aimery de

doi:10.1200/jco.2004.05.113

Cited by 2,696 publications

(1,807 citation statements)

References 24 publications

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“…However, the relative efficacy of these two regimens was directly compared in the randomised Tournigand trial (Tournigand et al, 2004). Although this study was primarily designed to investigate whether the sequence of administration of FOLFOX and FOLFIRI was important in terms of second PFS (the time from randomisation until disease progression after second-line therapy), it provides an important insight into the relative efficacies of these combinations in both the first-and second-line settings.…”

Section: Relative Efficacy Of First-line Combinationsmentioning

confidence: 99%

“…Oxaliplatin/5-FU/FA has been shown to prolong disease-free survival in patients undergoing curative resection for stage II and III CRC compared with 5-FU/FA alone (Andre et al, 2004), and has consequently been approved for the adjuvant therapy of patients with stage III CRC. It is likely that this will in turn lead to the increased use of irinotecan/5-FU/FA first-line for advanced disease.…”

Section: Choice Of First-line Treatment Following Adjuvant Therapymentioning

confidence: 99%

“…Overall survival data are eagerly awaited. (Rougier et al, 1998;de Gramont et al, 2000;Douillard et al, 2000;Maughan et al, 2002;Cunningham et al, 2004;Hurwitz et al, 2004;Tournigand et al, 2004) …”

Section: Bevacizumabmentioning

confidence: 99%

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Management of advanced colorectal cancer: state of the art

Saunders

Iveson

2006

Br J Cancer

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Colorectal cancer (CRC) caused over 500 000 deaths worldwide in 2002. Recent advances in the treatment of advanced disease include the incorporation of two new cytotoxic agents, irinotecan and oxaliplatin, into first-line regimens. The concept of planned sequential therapy involving three active agents during the course of a patient's treatment is evolving. Coupled with the integrated use of targeted monoclonal antibodies, we can now expect overall survival rates for advanced disease to exceed 20 months. This review considers current treatments and suggests where future progress may occur.

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Section: Relative Efficacy Of First-line Combinationsmentioning

confidence: 99%

Section: Choice Of First-line Treatment Following Adjuvant Therapymentioning

confidence: 99%

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Management of advanced colorectal cancer: state of the art

Saunders

Iveson

2006

Br J Cancer

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“…Indeed, regimens combining FU with IRI or l-OHP are equally effective in terms of response rate and overall survival (Tournigand et al, 2004) and represent the standard first-line treatment in advanced CRC (O'Neil and Goldberg, 2005). Although three combinations of IRI and FU (IFL, FOLFIRI and AIO þ IRI) have been evaluated in phase III studies (Saltz et al, 2000;Douillard et al, 2000;Köhne et al, 2005), several other schedules have been proposed (Venook, 2005;Atalay et al, 2003).…”

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confidence: 99%

Schedule-dependent activity of 5-fluorouracil and irinotecan combination in the treatment of human colorectal cancer: in vitro evidence and a phase I dose-escalating clinical trial

et al. 2006

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Several schedules of 5-fluorouracil (FU) and irinotecan (IRI) have been shown to improve overall survival in advanced colorectal cancer (CRC). Preclinical evidence suggests that the sequential administration of IRI and FU produces synergistic activity, although their clinical use has not been fully optimised. We investigated the interaction between short-term exposure to SN-38, the active metabolite of IRI, and prolonged exposure to FU in human CRC HT-29 cells and observed that the synergism of action between the two agents can be increased by extending the time of cell exposure to FU and reducing the interval between administration of the two agents. Based on these findings, we performed a phase I trial in 25 advanced CRC patients using a modified IRI/FU regimen as first-line therapy and evaluated three dose levels of IRI (150 -300 mg/m 2 ) and two of continuous infusion of FU (800 -1000 mg/m 2 ) in a 3-weekly schedule. The most severe grade III -IV toxicities were neutropoenia in four cycles and diarrhoea in three. One patient achieved complete response (4%), 12 a partial response (48%), the overall response rate was 52% (720, 95% CI); seven of 25 patients had stable disease (28%), the overall disease control was 80% (716, 95% CI). This modified IRI/FU schedule is feasible and exhibits potentially interesting clinical activity.

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“…The toxicity reported in the American studies was partially due to the different delivery schedule of CPT-11/LV/5-FU, and in a study in which CPT-11 was administered on a weekly basis, diarrhoea was reported in 88.9% of patients (Douillard et al, 2000). A recently published randomised phase III study has investigated the efficacy of the alternate sequence of administration of the FOLFIRI and FOLFOX regimens in the treatment of MCC (Tournigand et al, 2004). Second-line treatment with FOLFIRI achieved a 4% response rate with a 2.5 month median progression-free survival rate and overall survival of 20.6 months from the start of FOLFOX administered as first-line chemotherapy.…”

Section: Months)mentioning

confidence: 99%

Multicentre phase II study of bifractionated CPT-11 with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer pretreated with FOLFOX

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Saggio

Nuzzo³

et al. 2004

Br J Cancer

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This multicentre phase II study was designed to evaluate the antitumour activity and toxicity of bifractionated camptothecin (CPT-11) and 5-fluorouracil/ leucovorin (5-FU/LV) in the treatment of patients with metastatic colorectal cancer (MCC) who had been pretreated with 5-FU/LV-oxaliplatin (FOLFOX regimen). In all, 35 patients were enrolled in a two-stage trial. Treatment consisted of two daily doses of CPT-11, 90 mg m 2 administered over 90 min, followed by LV, 200 mg m 2 administered over 2 h plus 5-FU 400 mg m 2 as a bolus and 600 mg m 2 as a 22-h continuous infusion administered with disposable pumps as outpatient therapy. Toxicity was closely monitored. Response was evaluated by computed tomography scans every 8 weeks. All 35 patients were assessable for toxicity and response to treatment. Seven patients had a partial response, giving an overall response rate of 20%; 11 patients had stable disease (31.4%) and 17 progressed (48.5%). The median progression-free survival was 7.1 months and median survival was 14 months. A total of 10 patients (30%) experienced grade 3 -4 toxicity, including nausea (15%), diarrhoea (12%) and neutropenia (15%), while seven patients (21%) had grade 2 alopecia. The bifractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed substantial antitumour activity and was well tolerated in this group of patients with a poor prognosis, pretreated with the FOLFOX regimen.

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FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study

Abstract: Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.

Cited by 2,696 publications

References 24 publications

Management of advanced colorectal cancer: state of the art

Management of advanced colorectal cancer: state of the art

Schedule-dependent activity of 5-fluorouracil and irinotecan combination in the treatment of human colorectal cancer: in vitro evidence and a phase I dose-escalating clinical trial

Multicentre phase II study of bifractionated CPT-11 with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer pretreated with FOLFOX

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