Irinotecan, Oxaliplatin Plus Bolus 5-Fluorouracil and Low Dose Folinic Acid Every 2 Weeks

Abstract

The administration of a triple combination produced promising objective responses with acceptable toxicity but does not seem to produce an evident benefit in time-related parameters.

Efficacy and safety of chronomodulated irinotecan, oxaliplatin, 5‐fluorouracil and leucovorin combination as first‐ or second‐line treatment against metastatic colorectal cancer: Results from the International EORTC 05011 Trial

“…In the first‐line setting, these results compare favourably with literature reports in multicentre trials with conventional triplet regimens of the same drugs, FOLFIRINOX (irinotecan, fluorouracil, leucovorin, oxaliplatin) or FOLFOXIRI (folinic acid, 5‐fluorouracil, oxaliplatin and irinotecan), 17‐19 and even more so with less successful combination schedules 20‐23 . Similarly favourable appears the overall tolerability of frontline chronoIFLO5 (Table 2) comparatively to literature data 20‐23 . Moreover, although the current study was performed before molecular selection and targeted treatments became widely implemented, 24 the overall survival observed here (Figure 4A) is of the same order of magnitude as that in the most recent studies conducted in metastatic colorectal cancer 2 …”

“…In the first‐line setting, these results compare favourably with literature reports in multicentre trials with conventional triplet regimens of the same drugs, FOLFIRINOX (irinotecan, fluorouracil, leucovorin, oxaliplatin) or FOLFOXIRI (folinic acid, 5‐fluorouracil, oxaliplatin and irinotecan), 17‐19 and even more so with less successful combination schedules 20‐23 . Similarly favourable appears the overall tolerability of frontline chronoIFLO5 (Table 2) comparatively to literature data 20‐23 .…”

“…[20][21][22][23] Similarly favourable appears the overall tolerability of frontline chronoIFLO5 (Table 2) comparatively to literature data. [20][21][22][23] Moreover, although the current study was performed before molecular selection and targeted treatments became widely implemented, 24 the overall survival observed here (Figure 4A) is of the same order of magnitude as that in the most recent studies conducted in metastatic colorectal cancer. 2 In the second-line setting, limited evidence currently exists for the triplet combination, beside small single-institution studies.…”

“…ChronoIFLO5 confirmed in this international setting an altogether satisfactory tolerance, especially concerning hematotoxicity rates among the lowest ones in the literature without primary G-CSF prophylaxis (Table 2) for such highly effective triplet regimens. [17][18][19][20][21][22][23] For instance, a previous trial with conventional triplet reported an incidence of Grades 3 and 4 neutropenia of 50%, with 5% instances of febrile neutropenia. 18 Our findings here support prior evidence of a much lower neutropenia incidence with chronomodulated chemotherapy in comparison with conventional administration.…”

N3-o-toluyl-fluorouracil inhibits human hepatocellular carcinoma cell growth via sustained release of 5-FU

“…However, its half-life in plasma is very short (15–20 min), thus continuous intravenous administration is needed to maintain therapeutic concentrations [4, 5]. Moreover, the clinical dose of 5-FU is very close to its toxic dosage when given intravenously, resulting in significant toxicity to gastric and intestinal mucosa and bone marrow, making long-lasting treatment difficult [6, 7]. Hence, attempts have been made to develop oral prodrugs with sustained release of 5-FU at equal to or greater than its plasma concentrations that could be obtained by intravenous administration.…”