TY - JOUR
T1 - Protracted continuous infusion of 5-fluorouracil and low-dose leucovorin in patients with metastatic colorectal cancer resistant to 5-fluorouracil bolus-based chemotherapy
T2 - A phase II study
AU - Falcone, Alfredo
AU - Allegrini, Giacomo
AU - Lencioni, Monica
AU - Pfanner, Elisabetta
AU - Brunetti, Isa
AU - Cianci, Caudia
AU - Galli, Costanza
AU - Masi, Gianluca
AU - Antonuzzo, Andrea
AU - Conte, Pierfranco
PY - 1999
Y1 - 1999
N2 - Continuous-infusion (c.i.) 5-fluorouracil (5-FU) can overcome resistance to bolus 5-FU, and leucovorin (LV) enhances the cytotoxic effects of 5-FU, mainly when the duration of exposure to the latter is prolonged. The main objective of this study was therefore to determine the activity of a prolonged infusion schedule of 5-FU + LV in patients with metastatic colorectal cancer resistant to a 5-FU bolus-based chemotherapy. Only patients with metastatic measurable disease in progression during or within 2 months of the end of a 5-FU bolus ± LV-based chemotherapy were eligible for the study. 5-FU and 1-LV were given as a 14-day c.i. every 28 days, the 5-FU dose being 200 mg/m2 per day and the 1-LV dose being 5 mg/m2 per day. A total of 59 patients entered the study, of which 48 were resistant to 5-FU + LV and 11, to 5-FU + levamisole. Treatment was well tolerated, and WHO grade 3-4 toxicities were uncommon (11% of patients developed stomatitis and 7%, diarrhea). According to an intent-to-treat analysis, 10 of 59 patients obtained an objective response (1 complete response, 9 partial responses), for an objective response rate of 16% (95% confidence interval 8-25%). The median progression-free survival and overall survival were 4 and 9 months, respectively. The protracted 5-FU + LV c.i. schedule used in the present study is a well-tolerated and moderately active regimen in metastatic colorectal cancer patients resistant to 5-FU bolus ± LV. Only randomized studies can determine whether this palliative treatment has advantages in comparison with other second-line therapies such as 5-FU c.i. without LV, irinotecan, or oxaliplatin.
AB - Continuous-infusion (c.i.) 5-fluorouracil (5-FU) can overcome resistance to bolus 5-FU, and leucovorin (LV) enhances the cytotoxic effects of 5-FU, mainly when the duration of exposure to the latter is prolonged. The main objective of this study was therefore to determine the activity of a prolonged infusion schedule of 5-FU + LV in patients with metastatic colorectal cancer resistant to a 5-FU bolus-based chemotherapy. Only patients with metastatic measurable disease in progression during or within 2 months of the end of a 5-FU bolus ± LV-based chemotherapy were eligible for the study. 5-FU and 1-LV were given as a 14-day c.i. every 28 days, the 5-FU dose being 200 mg/m2 per day and the 1-LV dose being 5 mg/m2 per day. A total of 59 patients entered the study, of which 48 were resistant to 5-FU + LV and 11, to 5-FU + levamisole. Treatment was well tolerated, and WHO grade 3-4 toxicities were uncommon (11% of patients developed stomatitis and 7%, diarrhea). According to an intent-to-treat analysis, 10 of 59 patients obtained an objective response (1 complete response, 9 partial responses), for an objective response rate of 16% (95% confidence interval 8-25%). The median progression-free survival and overall survival were 4 and 9 months, respectively. The protracted 5-FU + LV c.i. schedule used in the present study is a well-tolerated and moderately active regimen in metastatic colorectal cancer patients resistant to 5-FU bolus ± LV. Only randomized studies can determine whether this palliative treatment has advantages in comparison with other second-line therapies such as 5-FU c.i. without LV, irinotecan, or oxaliplatin.
KW - 5-Fluorouracil
KW - Advanced disease
KW - Colorectal cancer
KW - Continuous infusion
KW - Drug resistance
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U2 - 10.1007/s002800050961
DO - 10.1007/s002800050961
M3 - Article
C2 - 10412951
AN - SCOPUS:0033028253
VL - 44
SP - 159
EP - 163
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 2
ER -