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.
A search of the literature did not find strong evidence to support the use of FOLFOX with trastuzumab in the treatment of HER2 positive, advanced gastric and gastro-oesophageal cancer. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by the retrospective study by Soularue et al.r
After an extensive review of the literature, only one study assessing the efficacy and safety of FOLFOX with trastuzumab was identified. This was a retrospective study by Soularue et al involving 29 patients treated with first line FOLFOX (oxaliplatin 85 mg/m², 5FU bolus 400 mg/m² and Leucovorin® 400 mg/m² on day 1, followed by 5FU 2,400 mg/m² over 46 hour continuous infusion every 2 weeks) with trastuzumab (6 mg/kg on cycle 1 day 1 followed by 4 mg/kg on day 1 for subsequent cycles). This study also included 5 patients treated with CAPOX and trastuzumab, and these patients were included in the efficacy analysis and toxicity reporting. Most of the patients included in this study were male (79%), with median age 63 years and ECOG 0-1 (79%). HER2 immunohistochemistry was 3+ in 88% of cases and IHC 2+/ISH positive in 12%.r
Source |
Study & year published |
Supports use |
Is the dose and regimen consistent with the protocol? |
Comments |
Observational study |
Soularue et al 2015r |
Yes |
Yes |
High dose FA |
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
V.3 2020 |
Yes |
Yes |
FA 400 mg/m², 5FU 2400 mg/m² CIV over 48 hours |
BCCA |
February 2019 |
Yes |
Yes |
FA 400 mg/m², up to 9 cycles |
CCO |
- |
N/A |
- |
- |
ESMO |
- |
N/A |
- |
- |
Efficacy
A summary of the evidence supporting the effect of this protocol is below.rr Efficacy data was reported in 30 patients with evaluable disease (included FOLFOX/trastuzumab and CAPOX/trastuzumab).
Outcome |
|
Median overall survival |
17.3 months |
Progression free survival |
9.0 months |
Response rate (partial) |
47% |
Stable disease |
17% |
Toxicity
A summary of the toxicities associated with this protocol are included in the table below. The most clinically significant toxicities for this treatment are neuropathy, neutropenia, anaemia and thrombocytopenia.
Toxicityr |
Any grade, n (%)
|
Grade 3-4, n (%) |
Neutropenia |
10 (29) |
3 (9) |
Thrombocytopenia |
17 (50) |
0 |
Anaemia |
20 (59) |
1 (3) |
Nausea |
16 (47) |
1 (3) |
Vomiting |
11 (32) |
0 |
Diarrhoea |
11 (32) |
0 |
Stomatitis |
11 (32) |
0 |
Neuropathy |
33 (97) |
6 (18) |
Hand foot syndrome |
11 (32) |
1 (3) |
Allergy |
2 (6) |
0 |
Alopecia |
1 (3) |
0 |
Cardiac |
0 |
0 |