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 protocol is provided by a phase 3, open-label, multicentre international randomised trial involving 1186 patients comparing panitumumab and FOLFIRI with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer.r
Between June 2006 and March 2008, 591 patients were randomised to receive panitumumab (6 mg/kg every 2 weeks) plus FOLFIRI and 595 patients received FOLFIRI alone on a 14 day cycle until disease progression or intolerability.
The primary end points were PFS and OS in patients with both wild type (WT) and mutated type (MT) KRAS tumours. Secondary endpoints included response rate, duration of response and safety.r
Although the FOLFIRI regimen used in these trials was not FOLFIRI (modified), there is no evidence to suggest any differences in efficacy resulting from calcium folinate dosing alterations. A discussion regarding the effect of dosing on outcome can be found in the calcium folinate (Leucovorin®) dose document.
After a median follow up of 13.3 months, there was a statistically significant improvement in PFS with panitumumab-FOLFIRI in the WT KRAS subpopulation. There was no significant difference seen in OS in the WT KRAS patients. For MT KRAS patients, no difference was seen for PFS or OS.r
WT KRAS patients
The median PFS was 5.9 months in the panitumumab-FOLFIRI group vs 3.9 months in the FOLFIRI group (HR=0.73; 95% CI 0.59 to 0.90; p=0.004).
(A) PFS WT KRAS (B) PFS MT KRAS (C) OS WT KRAS (D) OS MT KRASr
© J Clin Oncol 2010
|Efficacy WT KRASr
|Objective response rate (ORR) %
|Complete response (CR) %
|Partial response (PR) %
|Stable disease (SD) %
Treatment related adverse eventsr
© J Clin Oncol 2010