The evidence supporting the use of oxaliplatin and capecitabine CAPOX (XELOX) in gastric and gastroesophageal cancer is based on two randomised phase III trials (REAL-2r and ML17032r). REAL-2 showed that using capecitabine instead of fluorouracil (5-FU), and using oxaliplatin instead of cisplatin, was non-inferior in triplet regimens for advanced gastric and gastroesophageal cancer. Overall survival was numerically highest with EOX (compared to ECF, ECX and EOF).r ML17032 was a randomised study comparing the combination of cisplatin plus 5-FU (CF) to cisplatin plus capecitabine (CX) which also met its primary end point of non-inferiority of the capecitabine regimen in progression free survival (PFS) (non-inferiority margin of 1.25), with a median PFS of 5.6 months (CX) and 5 months (CF), and a HR of 0.81 (95% CI 0.63-1.04). Overall survival was similar, 10.5 months (CX) vs 9.3 months (CF), p=0.27. Response rate was superior with capecitabine, 41% (CX) v 29% (CF), p=0.03.r
In addition, the meta-analysis of REAL-2 and ML17032 by Okines et al showed superiority of capecitabine over 5-FU regimens.r
There are no randomised phase III studies comparing CAPOX to other first line regimens in metastatic gastric and gastro-oesophageal cancer, but several phase II studies have shown activity of CAPOX using capecitabine 1000 mg/m² BD days 1-14 and oxaliplatin 130 mg/m² intravenous on day 1, in 21-day cycles.
Source |
Study & year published |
Supports use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trials |
Dong et al 2009r |
Yes |
Yes |
|
|
Park et al 2008r |
Yes |
Yes |
|
|
Liu et al 2008r |
Yes |
Yes |
|
|
van Meerten et al 2007r |
Yes |
Yes |
|
|
Park et al 2006r |
Yes |
Yes |
|
|
Jatoi et al 2006r |
Yes |
Yes |
Capecitabine dose reduced to 850 mg/m² after 4 treatment related deaths |
Guidelines |
Date published/revised |
Supports use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
August 2020 |
Yes |
Yes |
N/A |
BCCA |
October 2020 |
Yes |
Yes |
N/A |
ESMO |
August 2016 |
Yes |
No doses stated |
N/A |
CCO |
- |
N/A |
- |
- |
Efficacy
A summary of the evidence supporting the effect of this protocol is below:
Outcome
|
Jatoi et al 2006r
|
van Meerten et al 2007r
|
Park et al 2006r
|
Park et al 2008r
|
Liu et al 2008r
|
Dong et al 2009r
|
Number of patients
|
43
|
51
|
20
|
54
|
68
|
44
|
Subtype
|
Advanced oesophageal, gastro-oesophageal junction, gastric cardia
|
Advanced oesophageal
|
Advanced gastric
|
Advanced gastric
|
Advanced gastric
Chinese patients
|
Advanced gastric
Elderly patients
|
Response rate (%)
|
35
(95% CI, 23-50%)
|
39
(19/49)
|
65
(95% CI, 44-86%)
|
63
(95% CI, 50-76%)
|
54.4
(95% CI, 42.6-66.2%)
|
51.2
(95% CI, 35.9-66.5%)
|
Complete response (%)
|
-
|
-
|
10
|
6
|
4
|
9
|
Time to progression (months)
|
4
(95% CI, 3.1-4.6)
|
5.3
|
7.5
(95% CI, 3.2-11.7)
|
5.8
(95% CI, 4.4-7.2)
|
5.7
(95% CI, 2.0-8.8)
|
5.6
(95% CI, 4.6-6.6)
|
Median OS (months)
|
6.4
(95% CI, 4.6–10)
|
8
(95% CI, 6–9)
|
Not reached
|
11.9
(95% CI, 8.8-15.1)
|
10.5
(95% CI, 5.0-15.1)
|
9.8
(95% CI, 7.4–12.2)
|
Toxicity
A summary of grade 3-4 toxicities:
Toxicity
|
Study
|
Incidence of event
|
Neutropenia
|
Park et al 2008r
|
8%
|
Thrombocytopenia
|
Park et al 2008r
|
11%
|
Anaemia
|
Dong et al 2009r
|
2%
|
Nausea
|
Jatoi et al 2006r
|
26%
|
Diarrhoea
|
Jatoi et al 2006r
|
26%
|
Vomiting
|
Jatoi et al 2006r
|
13%
|
Neuropathy
|
van Meerten et al 2007r
|
8%
|
Hand-foot syndrome
|
van Meerten et al 2007r
|
4%
|
There were 4 (9%) treatment-related deaths reported by Jatoi et al, which led to a protocol amendment with revised capecitabine dose of 850 mg/m².r