Evidence
Initially this protocol was the preferred regimen being more convenient and more commonly used. However, due to evidence from the Pancreox studyr being a negative trial with fluorouracil being statistically superior to FOLFOX6 and the CONKO-003 trialr demonstrating an improvement in overall survival in 168 patients it is the decision of the expert reference committee is to supersede this protocol with ID 1548 Pancreas metastatic OFF (oxaliplatin, fluorouracil, leucovorin) being the preferred therapy.
A search of the literature did not find strong evidence to support the use of FOLFOX in the treatment of advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. 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 phase II trial by Yoo et al.r
FOLFOX has been used extensively for the treatment of colorectal cancer. Due to the lack of conclusive evidence to identify the optimum dose of leucovorin, it is the consensus of the eviQ reference committee to adopt flat dosing of 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.
Source |
Study & year published |
Supports use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase III trials |
Pelzer et al 2011r |
Yes |
No |
OFF regimen
Oxal 85 mg/m2 day 8, 22
FA 50 mg & 5FU 2000 mg/m2 CIV over 24 hours day 1, 8, 15, 22
every 42 days |
Gill et al 2016r |
No |
No |
High dose FA |
Phase II trials |
Yoo et al 2009r |
Yes |
Yes |
High dose FA |
|
Tsavaris et al 2005r |
Yes |
No |
Oxal 50 mg/m2
FA 50 mg/m2
5FU 500 mg/m2
Weekly |
|
Novarino et al 2009r |
Yes |
No |
Oxal 40 mg/m2
5FU 500 mg/m2
FA 250 mg/m2
Weekly (3 weeks on, 1 week off) |
|
Ghosn et al 2007r |
Yes |
No |
Oxal 100 mg/m2
FA 400 mg/m2
5FU 400 mg/m2 then 3000 mg/m2 CIV
q14 days
1st line treatment |
Observational studies |
N/A |
N/A |
N/A |
- |
Case series |
N/A |
N/A |
N/A |
- |
Guidelines |
Date published/revised |
Supports use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
v1 2013 |
Yes |
No |
OFF regimen |
BCCA |
- |
N/A |
N/A |
- |
CCO |
- |
N/A |
N/A |
- |
N/A= not available
Efficacy
After a median follow-up of 24.4 weeks, the 6-month survival rate (primary end-point) was 27% in mFOLFIRI arm and 30% in mFOLFOX arm.r
Overall responser |
mFOLFIRI (%) |
mFOLFOX (%) |
Partial response |
0 |
7 |
Stable disease |
23 |
10 |
Progressive disease |
68 |
70 |
Not evaluable |
10 |
13 |
Disease control |
23 |
17 |
Survival curves for progression-free survival (PFS) and overall survival (OS)r
© British Journal of Cancer 2009
Toxicity
A summary of the toxicities associated with this protocol are included in the table below.
Grade 3/4 Toxicityr |
mFOLFIRI (%)
n=29 |
mFOLFOX (%)
n=29 |
Anaemia |
3 |
3 |
Neutropenia |
24 |
20 |
Thrombocytopenia |
3 |
3 |
Febrile neutropenia |
3 |
0 |
Alopecia |
0 |
0 |
Asthenia |
3 |
14 |
Diarrhoea |
7 |
0 |
Anorexia |
3 |
7 |
Nausea |
3 |
3 |
Vomiting |
10 |
10 |
Mucositis |
3 |
7 |
Neurotoxicity |
0 |
0 |