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.
Prior to the availability of irinotecan, oxaliplatin and bevacizumab, single agent weekly fluorouracil was the preferred treatment option for patients with metastatic colorectal cancer. Combination therapies which include fluorouracil have improved response rates and survival compared with weekly fluorouracil. For this reason, combination therapy is usually the treatment of choice for first line therapy in patients with good performance scores.
Capecitabine is an alternative to intravenous fluorouracil. Two trials have compared capecitabine with 5FU/Leucovorin (Mayo regimen) in first line metastatic setting.r,r These studies showed higher response rates in capecitabine arms and no signficant difference in TTP, PFS and OS. There was less grade 3/4 stomatitis, neutropenia, diarrhoea, nausea and vomiting and more hand and foot syndrome in the capecitabine arms.
The highest level of evidence supporting the activity of weekly fluorouracil (5-FU) plus leucovorin (Roswell Park) comes from studies conducted in the adjuvant setting.r It is this evidence that is used to support the use of Roswell Park in the metastatic setting.
Between August 1987 and April 1989, a total of 1081 patients were enrolled into the study and randomly assigned to receive either 5-FU 325 mg/m2/day on days 1-5 and 375 mg/m2/day on days 36-40, lomustine 130 mg/m2 on day 1 and vincristine 1 mg/m2 (max 2mg) on days 1 and 36 or 5-FU 500 mg/m2 and leucovorin 500 mg/m2 weekly for 6 weeks followed by 2 weeks break.
The primary end points of the study were disease-free survival and overall survival.r
Efficacy
After a follow-up of 3 years, the DFS rate and OS rate for 5-FU/FA versus MOF were 73% vs 64% and 84% vs 77% respectively. This translates to a 30% and 32% risk reduction in treatment failure and mortality respectively in patients receiving 5-FU/FA compared to MOFr.
Disease-free survivalr
© Journal of Clinical Oncology 1993
Overall survivalr
© Journal of Clinical Oncology 1993
Toxicity
Toxicityr |
FULV |
FLOX |
p-value |
Grade |
3 |
4 |
3 |
4 |
|
Diarrhoea |
32 |
<1 |
37 |
1 |
0.003 |
Dehydration |
11 |
<1 |
16 |
1 |
< 0.001 |
Nausea |
11 |
0 |
16 |
0 |
< 0.001 |
Vomiting |
8 |
<1 |
12 |
< 1 |
< 0.001 |
Fatigue |
3 |
<1 |
5 |
< 1 |
0.15 |
Neurosensory |
<1 |
0 |
8 |
0 |
< 0.001 |
Thrombosis or embolism |
4 |
1 |
3 |
1 |
0.78 |
© Journal of Clinical Oncology 2007