Due to the lack of conclusive evidence to identify the optimum dose of calcium folinate (Leucovorin®), it is the consensus of the eviQ reference committee to adopt flat dosing of calcium folinate (Leucovorin®) as a 50 mg IV bolus when used with bolus 5FU across all colorectal and upper gastrointestinal protocols. A discussion regarding the effect of dosing on outcome can be found in the calcium folinate (Leucovorin®) dose document.
The evidence supporting this treatment comes from a randomized phase IV trial by Ackland et al evaluating the safety and efficacy of bevacizumab and FOLFIRI as first line treatment for metastatic colorectal cancer.
209 patients were enrolled in 2005 at 31 centres, median age was 62 years, median follow-up was 13.1 months and median duration of treatment was 9.2 months with bevacizumab and 6.5 months with FOLFIRI.
The primary objective was progression free survival, secondary objective was safety, overall response rate and duration of response and overall survival.r
This trial followed on from the Hurwitz trial showing improved survival with addition of bevacizumab to irinotecan based chemotherapy.r Application of the Hurwitz trial is limited by the use of the more toxic IFL combination.
Although the Bevacizumab, FOLFIRI regimen used in these trials was not Bevacizumab, FOLFIRI (modified), there is no evidence to suggest any differences in efficacy resulting from alterations in the folinic acid dosing.
Ackland et al reported the following:
The overall response rate was 53.1% and 32.5% of patients had stable disease. Median PFS and OS (11.2 and 22.2 months, respectively).r
This compared to the PFS and OS observed in the Bevacizumab IFL trial by Hurwitz et al of 10.6 and 20.3 months respectively.r
Progression free survivalr
© New England Journal of Medicine 2004
The proportion of patients with venous thrombosis was higher than previous studies and is thought to be due to the inclusion of CVAD related thrombus being included in the term venous thrombosis or a difference in coding conventions.
Adverse events leading to discontinuation of any kind of study component occurred in 24% of patients most commonly GI disorders.
There were 13 deaths not due to disease progression, pulmonary embolism (2), myocardial infarction (1), aortic dissection (1), hepatic failure (1), cardiac arrest (1), large intestinal perforation (1), neutropenic sepsis (1), tumour haemorrhage (1), small intestinal obstruction (1) and unknown (2).
The 60 day mortality rate 2%.r
|Grade 3 to 5 adverse eventsr