Dr Burge and colleagues from England investigated 2-weekly intravenous irinotecan combined with oral capecitabine in advanced gastroesophageal adenocarcinoma.
During Phase I, the team escalated doses in chemotherapy naïve or pretreated patients to establish maximum tolerated doses.
In Phase II, patients were treated at maximum tolerated doses as first-line therapy with the primary end point of RECIST response.
Doses for Level 1 in phase I were irinotecan 150 mg m-2 on day 1, and capecitabine 850 mg m-2 12-hourly on days 1 to 9.
Level 2 was similar to Level 1, excepting capecitabine, which was dosed at 1000 mg m-2.
Level 3 was similar to Level 2 but included irinotecan 180 mg m-2.
|The most common grade 3 to 4 toxicities were lethargy, diarrhoea, nausea, and anorexia|
|British Journal of Cancer|
The team reported that Level 4 was as level 3 but capecitabine was increased to1250 mg m-2.
The research team entered 21 patients in Phase 1, and the maximum tolerated dose was Level 3.
The team noted that dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis.
In Phase II, 31 patients were entered at Level 3.
The researchers found that during the first 6 cycles, 13 of these patients underwent dose reduction and 3 patients stopped treatment for toxicity.
A further 6 patients stopped for progressive disease.
The team observed that the most common grade 3 to 4 toxicities were lethargy, diarrhoea, nausea, and anorexia.
The researchers noted no treatment-related deaths, and the median overall survival was 10 months.
The response rate was 32%.
Dr Burge's team concluded, “This regimen is active in gastroesophageal adenocarcinoma.”
“However, using the maximum tolerated doses defined in Phase I, fewer than 50% patients tolerated 6 cycles without modification in Phase II.”
“Therefore, modification of these doses is recommended for further study.”