Transcript Slide 1

Capecitabine and Oxaliplatin for
Advanced Esophagogastric Cancer
NEJM January 3, 2008
Authors: David Cunningham et al
Date posted: April 3, 2008
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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
R
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
Epirubicin 50 mg/m2 IV q 3 weeks
Cisplatin 60 mg/m2 IV q 3 weeks
Capecitabine 625 mg/m2 bid continously
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
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
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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
NS
11.2 mos
Non-inferiority of 5FU/cape and cis/oxali
established
OS
(median,
mos)
9.9 mos
9.9 mos
9.3 mos
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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 0.66-0.97 – 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
11.4% overall
• rate was significantly greater in cisplatin group compared to
oxaliplatin group (15.% vs 7.6%, P<0.001).
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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.
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