CPT-11 (Irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer

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

“…This hypothetical mechanism of action provides a molecular rationale to our results showing that the synergistic activity of the SN-38 and FU sequence is partially conserved in colon carcinoma cells resistant to FU and characterised by increased levels of TS. It is also in agreement with the clinical observation that the FU-and IRI-based combination therapy is effective in patients pretreated with FU (Andre et al, 1999) and whose tumours are generally characterised by increased levels of TS (Wong et al, 2001) as well as with our results obtained in three patients previously treated with FU-based adjuvant chemotherapy who achieved partial response with this modified FU/IRI regimen. Furthermore, our results suggest that IRI-resistant CRC cells may be more sensitive to schedules with c.i.…”

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

“…Grade 3/4 neutropenia was 17% with the modified de Gramont regimen, a little lower than Irinotecan and infusional 5-FU in colorectal cancer P Leonard et al that reported by Douillard et al (2000), and similar to the level reported by André et al (1999). The dose of 5-FU was initially set at 2.8 g m 72 over 46 h as the FOLFIRI regimen reported by André et al (1999) had used higher doses of 5-FU 2.4 -3.0 g m 72 in combination with irinotecan. The first four patients enrolled in our study received the higher dose of 5-FU and two died on treatment.…”

“…This was much less than the reported incidence of diarrhoea in the study by Douillard et al (2000) However, in their trial, patients received either the classical de Gramont regimen or a weekly high dose infusional 5-FU regimen (Köhne et al, 1998). Grade 3/4 neutropenia was 17% with the modified de Gramont regimen, a little lower than Irinotecan and infusional 5-FU in colorectal cancer P Leonard et al that reported by Douillard et al (2000), and similar to the level reported by André et al (1999). The dose of 5-FU was initially set at 2.8 g m 72 over 46 h as the FOLFIRI regimen reported by André et al (1999) had used higher doses of 5-FU 2.4 -3.0 g m 72 in combination with irinotecan.…”

“…(Guichard et al, 1998) Combination studies with the de Gramont regimen have established a 2 weekly dose of irinotecan 180 mg m 72 is acceptable (Ducreux et al, 1999;André et al, 1999). Our study was designed to examine the activity and toxicity of combining irinotecan and the modified de Gramont regimen as first-or second-line therapy of metastatic colorectal cancer.…”

“…A 'Modified de Gramont' (MdG) regimen has been developed in which a 2-h infusion of a fixed dose of folinic acid is followed by 5-FU bolus then a high dose 46-h 5-FU infusion (de Gramont et al, 1998;André et al, 1999). This regimen, alone or with oxaliplatin, has now been optimised Cheeseman et al, 2002).…”