TY - JOUR
T1 - Randomised trial comparing three different schedules of infusional 5FU and raltitrexed alone as first-line therapy in metastatic colorectal cancer
T2 - Final results of the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 trial
AU - Ducreux, M.
AU - Bouche, O.
AU - Pignon, J. P.
AU - Mousseau, M.
AU - Raoul, J. L.
AU - Cassan, P.
AU - Leduc, B.
AU - Berger, C.
AU - Dunant, A.
AU - Fournet, J.
AU - Bedenne, L.
PY - 2006/7/1
Y1 - 2006/7/1
N2 - LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m 2), followed by an intravenous bolus of 5FU (400 mg/m 2), followed by a 22-hour continuous infusion of 5FU (600 mg/m 2) on day 1 and day 2/2 weeks (IdLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m 2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex® arm; 3 mg/m 2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, IdLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, IdLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, IdLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or IdLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that IdLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.
AB - LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m 2), followed by an intravenous bolus of 5FU (400 mg/m 2), followed by a 22-hour continuous infusion of 5FU (600 mg/m 2) on day 1 and day 2/2 weeks (IdLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m 2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex® arm; 3 mg/m 2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, IdLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, IdLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, IdLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or IdLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that IdLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.
KW - 5-Fluorouracil
KW - Colorectal cancer
KW - Continuous infusion
KW - Leucovorin
KW - Raltitrexed
UR - http://www.scopus.com/inward/record.url?scp=33746608458&partnerID=8YFLogxK
U2 - 10.1159/000094357
DO - 10.1159/000094357
M3 - Article
C2 - 16816536
AN - SCOPUS:33746608458
SN - 0030-2414
VL - 70
SP - 222
EP - 230
JO - Oncology (Switzerland)
JF - Oncology (Switzerland)
IS - 3
ER -