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 based upon data presented at ASCO Annual meeting 2017. It is important to note that this data has not yet been published in a peer-reviewed journal.
FLOT4 was a phase 3 German, randomised trial involving 716 patients comparing FLOT with ECF/ECX in patients with T2-4/cN-any or cT-any/cN+ gastric cancer or adenocarcinoma of the gastro-oesophageal junction.r
Between August 2010 and Feb 2015, 356 patients were randomised to receive either 4 cycles of 5FU at 2600 mg/m2, leucovorin 200 mg/m2, oxaliplatin 85 mg/m2 and docetaxel 50 mg/m2 fortnightly for four neoadjuvant cycles, followed by a further four cycles post-operatively. This was compared to 360 patients who received ECX/ECF three weekly for three neoadjuvant cycles and a further three cycles post-operatively. The majority of patients were gastro-oesophageal adenocarcinoma, with 44% in each group respectively (160 in ECF/ECX & 158 in FLOT) being gastric adenocarcinoma.r
The primary end point was overall survival (OS), and the secondary end points were progression free survival (PFS), complete resection rate, surgical morbidity and mortality and chemotherapy related toxicity.
After a median follow up of 43 months, the median OS was 50 months in the FLOT group, compared with 35 months in the ECF/ECX group (HR=0.77, CI 95% 0.63-0.94; p=0.012). The study was not powered to assess significance across anatomical subgroups.r
With regards to secondary outcomes, patients treated with FLOT had significantly longer PFS of 30 months, compared with 18 months in ECF/ECX, HR=0.75 (95% CI 0.62-0.91), p=0.004. There were significantly higher rates of R0 resections in the FLOT group 84%, compared with 77% in those treated with ECX/ECF. There were no significant differences between the two groups with respect to surgical morbidity and mortality, with 55% of patients in both groups respectively experiencing a post-operative complication.r
Kaplan-Meier curves for overall survival r
© ASCO 2017
There was no difference in the incidence of chemotherapy toxicities, with 61% of patients treated with FLOT and 62% of ECX/ECF patients experiencing any toxicity. 90% of patients treated with FLOT and 91% of those treated with ECF/ECX completed their neo-adjuvant chemotherapy, whilst 46% in the FLOT group and 37% in the ECF/ECX group completed their adjuvant/post-operative chemotherapy. Quality of life data was not captured.r
© ASCO 2017