Semimonthly Versus Monthly Regimen of Fluorouracil and Leucovorin Administered for 24 or 36 Weeks as Adjuvant Therapy in Stage II and III Colon Cancer: Results of a Randomized Trial

Abstract

Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.

Adjuvant sequential methotrexate → 5-fluorouracil vs 5-fluorouracil plus leucovorin in radically resected stage III and high-risk stage II colon cancer

“…Despite a certain percentage of missing data regarding patient and tumour characteristics, understandable in a large pragmatic trial, the overall good quality of colon cancer care in this trial is proven by two indirect indicators: the median number of lymph nodes removed at surgery, 12, and the very good 3-year DFS value, 74%. This value matches well with that of the control arm of the MOSAIC (Andre et al, 2004) study (73%), which in turn was identical to another European large study of adjuvant chemotherapy in this disease (Andre et al, 2003).…”

“…Despite a certain percentage of missing data regarding patient and tumour characteristics, understandable in a large pragmatic trial, the overall good quality of colon cancer care in this trial is proven by two indirect indicators: the median number of lymph nodes removed at surgery, 12, and the very good 3-year DFS value, 74%. This value matches well with that of the control arm of the MOSAIC (Andre et al, 2004) study (73%), which in turn was identical to another European large study of adjuvant chemotherapy in this disease (Andre et al, 2003).The large sample size of the study and the similarity of the OS and DFS curves in the two arms fail to demonstrate clinically relevant differences in efficacy between the regimens. Since the toxicity and duration of the two treatments are also similar, MTX-FU may be considered an alternative to FU þ LV, but offers no advantage, even from the convenience standpoint.…”

“…Other issues have been addressed and definitely answered by large-scale randomised trials in the last 5 years. Such is the case for the optimal dose of LV to potentiate FU: no need for high dose (Haller et al, 1998;Quasar, 2000); the best schedule of FU LV: equivalence between the weekly and the monthly schedule (Kerr, 2000), the lack of efficacy of levamisole (Haller et al, 1998;Quasar, 2000), the equivalence of the bolus and infusional FU regimens (Andre et al, 2003) and the inefficacy of short-term early postoperative intraportal FU infusions (Liver infusion meta-analysis group, 1997).INTACC is an Italian intergroup that has recently reported another large-scale randomised trial of adjuvant chemotherapy for colon cancer comparing FU levamisole vs FU LV levamisole (Di Costanzo et al, 2003). When the accrual of that first study was completed in February 1995, levamisole was still considered part of the standard adjuvant treatment.…”

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

“…Protracted infusional regimes were developed to maximise 5FU dose intensity. They have been found to be as effective as the bolus regimens and less toxic, with less impact on quality of life (Andre et al, 2003;Saini et al, 2003;Goyle and Maraveyas, 2005 (Goyle and Maraveyas, 2005). The other major factor likely to result in failure to complete chemotherapy is toxicity.…”

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

“…This is a central confounding issue as stage-III CRC patients are conventionally treated with FOLFOX adjuvant chemotherapy (Andre et al, 2003;Haller et al, 2011;Kuebler et al, 2007). Analyses of stage-III CRC patients who received adjuvant FOLFOX, carried out retrospectively, suggest that MSI CRCs may be sensitive to oxaliplatin (Trouilloud et al, 2011;Zaanan et al, 2011).…”