1. Authors: David Cunningham et al Date posted: April 3, 2008
Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer NEJM January 3, 2008
Authors: David Cunningham et al
Date posted: April 3, 2008

2. R Epirubicin 50 mg/m2 IV q 3 weeks Cisplatin 60 mg/m2 IV q 3 weeks
Treatment A: ECF
Epirubicin 50 mg/m2 IV q 3 weeks
Cisplatin 60 mg/m2 IV q 3 weeks
5-FU 200 mg/m2 per day continuous infusion
Treatment B: ECX
Epirubicin 50 mg/m2 IV q 3 weeks
Cisplatin 60 mg/m2 IV q 3 weeks
Capecitabine 625 mg/m2 bid continously R
Treatment C: EOF
Epirubicin 50 mg/m2 IV q 3 weeks
Oxaliplatin 130 mg/m2 IV q 3 weeks
5-FU 200 mg/m2 per day continuous infusion
1002 patients
locally advanced (inoperable) or metastatic (80%) cancer esophagus, GE junction,gastric
- Adenocarcinoma, squamous cell, or undiff. carcinoma
- 2x2 non-inferiority design
- Primary Enpoint: non
inferiority in OS
Treatment D: EOX
Epirubicin 50 mg/m2 IV q 3 weeks
Oxaliplatin 130 mg/m2 IV q 3 weeks
Capecitabine 625 mg/m2 bid continously

3. RESULTS Patients 85-90% in all groups were adenocarcinoma
Relatively even distribution among: esophagus, GE junction, stomach
ECF
ECX
EOF
EOX
p-value
Response Rate (%)
41%
46%
42%
48% NS
PFS (median, mos)
6.2 mos
6.7 mos
6.5 mos
7.0 mos OS
(median, mos)
9.9 mos
9.3 mos
11.2 mos
Non-inferiority of 5-FU/cape and cis/oxali established

4. STUDY COMMENTARY
This large RCT demonstrated non-inferiority for 5-FU/capecitabine and cisplatin/oxaliplatin when given with epirubicin in patients with advanced esophagogastric cancer.
In planned survival analysis among 4 groups, survival in EOX group was improved compared to ECF (HR 0.80, 95%CI – Median Survival improved from 9.9 to 11.2 mos).
No significant difference in overall toxicity or QOL between the 4 arms.
Oxaliplatin had more grade 3-4 diarrhea and neuropathy than cisplatin but less neutropenia and alopecia
greater grade 3-4 neutropenia (but no higher rates of febrile neutropenia) and HFS (10% vs 4%) in ECX group versus ECF
High rate of thromboembolism % overall
rate was significantly greater in cisplatin group compared to oxaliplatin group (15.% vs 7.6%, P<0.001).

5. CANADIAN MEDICAL ONCOLOGISTS
BOTTOM LINE FOR
CANADIAN MEDICAL ONCOLOGISTS
In many Canadian centres the standard of care for this patient population is ECF. This study shows that capecitabine can be safely substituted for infusional 5-FU in patients with advanced esophagogastric cancer.
This provides a treatment option for patients which is free of pumps and venous access devices – the only downside being slightly higher rates of Gr 3/4 HFS.
The use of oxaliplatin avoids the requirement of IV hydration used with cisplatin and there is a signal of improved efficacy with this agent. However, the overall toxicity and QOL was not improved with the substitution of oxaliplatin for cisplatin.
Given the greater ease of delivery it is likely that EOX and/or ECX will emerge in the future as preferred standards compared to ECF but access to oxaliplatin and capecitabine for advanced gastric cancer will likely depend on funding of these agents in most parts of Canada.