Professor Cunningham and colleagues from England established the optimal dose of capecitabine to be used within a multicenter.
The researchers designed a randomized study evaluating the potential roles of oxaliplatin and capecitabine in chemonaive patients with advanced oesophagogastric cancer.
The research team randomized patients to 4 combination treatment regimens and stratified for extent of disease, performance status and center.
The treatments included epirubicin, cisplatin, 5-fluorouracil as Group 1, and epirubicin, oxaliplatin, 5-fluorouracil as Group 2.
| Response rate was 48% for the epirubicin, oxaliplatin, capecitabine combination group|
|British Journal of Cancer|
Treatment regimes in Group 3 included epirubicin, cisplatin, capecitabine and Group 4 was given epirubicin, oxaliplatin, capecitabine.
The team gave weekly doses of 50 mg/m2 of epirubicin, 60 mg/m 2 capecitabine, and 130 mg/m of oxaliplatin.
The researchers gave 5-fluorouracil intranvenously at a dose of 200 mg/m2 per day and capecitabine at 500 mg/m2 escalating to 625 mg/m2/bid after the first interim analysis results.
The researchers performed the first interim analysis when 80 patients had been randomized.
The team reported that dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema and diarrhoea.
The research team noted that 5% of capecitabine treated patients experienced grade 3 to 4 toxicity.
The protocol planned dose escalation of capecitabine to 625 mg/m2/bid was instituted and a second interim analysis was performed by the researchers.
The team reported that a total of 204 patient were randomized at the time of the protocol planned second interim analysis.
The researchers observed grade 3 to 4 fluoropyrimidine-related toxicity in 14% receiving 5-fluorouracil, 8% receiving capecitabine of 500 mg/m2/bid and 15% receiving capecitabine 625 mg/m2/bid.
Combined complete and partial response rates were 31% with epirubicin, cisplatin, 5-fluorouracil and 39% with epirubicin, oxaliplatin, 5-fluorouracil.
The team also found that response rates for the epirubicin, cisplatin, capecitabine group was 35% and 48% for epirubicin, oxaliplatin, capecitabine group.
Professor Cunningham's team concluded, “Grade 3 to 4 fluoropyrimidine toxicity affected 15% of patients treated with capecitabine 625 mg m-2/bid, which is similar to that observed with 5-fluorouracil, confirming this to be the optimal dose."
“The replacement of cisplatin by oxaliplatin and 5-fluorouracil by capecitabine does not appear to impair efficacy.”
“The trial will continue to total accrual of 1000 patients.”