Phase II study of radiochemotherapy with uft and low-dose oral leucovorin in patients with unresectable rectal cancer

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

“…response seems to be greater than that observed with radiotherapy alone (4%) (Frykholm et al, 2001) and comparable with most other fluoropyrimidine CRT regimens (12 -28%) (de la Torre et al, 1999;Freyer et al, 2001;Frykholm et al, 2001;Carraro et al, 2002;Gérard et al, 2003;Aschele et al, 2005;Loi et al, 2005;Avallone et al, 2006;Klautke et al, 2006;Pucciarelli et al, 2006;Ryan et al, 2006). Four (15%) patients in the current study had microfocal residual disease, meaning overall that nine (29% of the phase II patient population) patients had a complete, or almost complete, response to treatment.…”

“…Furthermore, the resection rate achieved in this study is higher than that observed in studies using radiotherapy alone (range, 64 -75%) (Emami et al, 1982;Frykholm et al, 2001) or in some studies of CRT regimens (62 -95%) (de la Torre et al, 1999;Frykholm et al, 2001;Klautke et al, 2006;Glynne-Jones et al, 2007), and it is comparable to that cited in other reports of research with irinotecan (90 -100%) (Minsky et al, 1999;Mitchell et al, 2004;Klautke et al, 2005;Sebag-Montefiore et al, 2005). It is worth noting, that this current trial included only patients with T3/T4 cancers-that is patients with more advanced disease than those included in previously published studies.…”

“…Considering CRM involvement, 81% of patients in this study who underwent TME surgery were classed as R 0 after surgery (CRM-negative). In studies that report data on the number of CRM-negative cases, results range from 61 -74% with radiotherapy (Emami et al, 1982;Frykholm et al, 2001) to 72 -89% with 5-FUbased protocols (de la Torre et al, 1999;Frykholm et al, 2001;Avallone et al, 2006;Klautke et al, 2006;Glynne-Jones et al, 2007) or 88 -89% when irinotecan is given as part of the CRT regimen (Klautke et al, 2005;Sebag-Montefiore et al, 2005). The addition of irinotecan to CRT regimens does not, therefore, seem to increase the high rate of CRM-negative surgery reported previously, but CRT certainly seems to be more successful than radiotherapy alone.…”

“…A negative CRM may provide an early surrogate test of efficacy and a predictor of local recurrence, enabling the rapid evaluation of the many new treatment regimens currently being investigated (Cunningham et al, 2002). Patients who respond to pre-operative chemo-radiation have improved disease-free and overall survival compared with non-responders (Janjan et al, 2001).…”

“…These include raltitrexed, irinotecan, oxaliplatin and oral fluoropyrimidines, including uracil-tegafur and capecitabine (de la Torre et al, 1999;Kalofonos et al, 2003;Fernandez-Martos et al, 2004;Gambacorta et al, 2004a, b;Hofheinz et al, 2005;Klautke et al, 2005Klautke et al, , 2006. Despite the advent of oral fluoropyrimidines, intravenous infusion remains popular in Europe and the United States, because nausea, vomiting and diarrhoea can affect compliance and absorption of oral drugs (Minsky et al, 1993;Rodel et al, 2000;Mohiuddin et al, 2006).…”