A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

Abstract

We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m À2 on day 1; capecitabine 850 mg m À2 12-hourly on days 1 -9. Level 2: as level 1 but capecitabine 1000 mg m À2 . Level 3: as level 2 but irinotecan 180 mg m À2 . Level 4: as level 3 but capecitabine 1250 mg m À2 . In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3 -4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16 -52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.

A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer

“…Moreover, the results achieved in this study could be favourably comparable with those of other studies that used an irinotecanbased combination regimen (Pozzo et al, 2004;Baek et al, 2006). Biweekly irinotecan and capecitabine (180 mg m À2 , day 1 and 2000 mg m À2 , days 1 -9, respectively) have also been studied against gastroesophageal cancer (Burge et al, 2006), and an overall response rate of 32% was obtained. Because previous studies have produced improved results for dose-intensified biweekly capecitabine against colorectal cancer, in the present study, we adopted this dose and schedule for capecitabine instead of the conventional triweekly regimen against gastric cancer.…”

“…However, grade 3 or 4 diarrhea occurred in only two patients (3.6%) each. Moreover, this 7.2% rate of grade 3 or 4 diarrhea was less than that observed in other studies, which reported rates of 15 -22% Baek et al, 2006;Burge et al, 2006). The diarrhea and hand -foot syndrome were doselimiting toxicities in phase I studies using capecitabine (Budman et al, 1998;Mackean et al, 1998).…”

Gastric cancer: surgery in 2011

“…Only in few phase II trials with induction therapy RECIST criteria have been used so far [64][65][66]. Careful clinical response evaluation by a combination of endoluminal ultrasound, endoscopy, and CT scan used for restaging is predictive of histopathological regression and prognosis in experienced centers [3,4,8,21,25].…”

Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis

“…Although the frequency of grade 3/4 toxicities occurring with capecitabine alone or in combination with lapatinib has been reported to be very low (0-1%), the oral adverse event described as stomatitis and/or mucositis [6,7] occurs at a frequency of 11-15% (all grades) [2,3].…”