Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer

Rougier, Philippe; Cutsem, Éric Van; Bajetta, Emilio; Niederle, N.; Possinger, K.; Labianca, Roberto; Navarro, Matilde; Morant, Rudolf; Bleiberg, Harry; Wils, J.; Awad, Lucile; Hérait, Patrice; Jacques, Christian

doi:10.1016/s0140-6736(98)03085-2

Cited by 928 publications

(432 citation statements)

References 14 publications

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“…The importance of effective second-line therapy was first highlighted by the early phase III trials in which single-agent irinotecan was used as salvage therapy (Cunningham et al, 1998;Rougier et al, 1998). The FOLFIRI/FOLFOX crossover in the Tournigand study achieved the longest survival recorded to date, for a phase III trial in advanced CRC.…”

Section: The Influence Of Second-line Therapy On Survivalmentioning

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: The Influence Of Second-line Therapy On Survivalmentioning

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%

Management of advanced colorectal cancer: state of the art

Saunders

Iveson

2006

Br J Cancer

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“…These clinical results confirm previous preclinical data indicating synergistic effects when combining these drugs (Raymond et al, 1997;Fischel et al, 1998). In the same way, CPT11 alone is active in colon cancer and, interestingly, in patients refractory to FU (Cunningham et al, 1998;Rougier et al, 1998). More recently, it has been shown that the CPT11-FUFA combination produced a higher response rate (Douillard et al, 2000;Saltz et al, 2000) and prolonged survival (Douillard et al, 2000) in comparison to FUFA in advanced colorectal cancer patients.…”

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confidence: 96%

Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines

et al. 2001

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Summary A marked antitumour efficacy is currently obtained by oxaliplatin (LOHP)-fluorouracil (FU)-folinic acid (FA) combination and by CPT11-FU-FA combination. Logically, the triple association LOHP, CPT11 and FUFA will be soon tested in cancer patients. The aim of the present study was to compare two schedules combining SN38 (the active metabolite of CPT11, irinotecan) with FU-FA and LOHP. The two schedules differed by the SN38 position. The relative contribution of each drug in the resulting global cytotoxicity was evaluated. Two human colon cancer cell lines were used (WIDR and SW620 both p53 mutated). LOHP plus FA were applied for 2 h, just before a 48 h FU exposure. The SN38 sequence was applied for 24 h, starting either 48 h before LOHP-FA (schedule A), or just after LOHP-FA exposure (schedule B). Cytotoxicity was assessed by the 3-(4,5-demethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test and drug interactions were analysed according to the Chou and Talalay method, based on the computation of a combination index (CI). The SN38 position significantly induces a shift from additivity-antagonism when SN38 was applied after LOHP, towards additivity-synergism when SN38 was applied first (P = 0.03). The relative contribution (RC) of each drug in the overall cytotoxicity of the triple combination was defined as the drug concentration giving 50% cell lethality (IC 50 ) of the double association without that drug divided by the IC 50 of the triple association. Whatever the SN38 position, the larger contribution was made by LOHP (median RC = 2.4) and the smaller by SN38 (median RC = 1.1). In addition, the contribution of FUFA was improved when SN38 was applied first (median RC = 2.2) as compared to the opposite schedule (median RC = 1.2). Results were in agreement between the two explored cell lines. The present data should be taken into account when establishing the rationale of future trials combining CPT11, LOHP and FU-FA.

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“…In second-line therapy, the association of L-OHP with 5-FU/LV in the treatment of patients with MCC progressing after CPT-11/5-FU/LV (FOLFIRI regimen) has been shown to be beneficial (Rothenberg et al, 2003) and limited data from literature exist on the salvage treatment of patients with MCC progressing after the FOLFOX regimen. In patients with resistance to 5-FU bolus, CPT-11 has been shown to be superior both with respect to best supportive care and to 5-FU continuous infusion (Cunningham et al, 1998;Rougier et al, 1998). A modest survival gain was obtained with this treatment, but was accompanied by severe gastrointestinal toxicity, with an elevated percentage of patients having to be hospitalised during the course of chemotherapy.…”

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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

Recchia

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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Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer

Cited by 928 publications

References 14 publications

Management of advanced colorectal cancer: state of the art

Management of advanced colorectal cancer: state of the art

Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines

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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