Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group

Abstract

BACKGROUND: Combination chemotherapy is standard treatment for metastatic colorectal cancer (MCRC). The aim of this study was to determine the efficacy and safety of capecitabine þ irinotecan (2-weekly schedule), as first-line therapy of MCRC. METHODS: Patients received irinotecan 175 mg m À2 on day 1 and oral capecitabine 1000 mg m À2 twice daily on days 2 -8 every 2 weeks. For patients aged X65 years, the starting doses of irinotecan and capecitabine were reduced to 140 and 750 mg m À2 , respectively. RESULTS: A total of 53 patients were enrolled: 29 (55%) were X65 years old. In an intention-to-treat analysis, complete response was achieved in three patients for an overall response rate (ORR) of 32%. The disease control rate (ORR þ stable disease) was 66% and the median duration of response was 7.3 months. Median time to progression and overall survival were 9.0 and 19.2 months, respectively. Grade 4 neutropenia was reported in one patient: no other grade 4 toxicities were recorded. Grade 3 diarrhoea occurred in 8 (15%) patients and grade 1 -2 hand -foot syndrome in 7 (13%) patients. CONCLUSION: Capecitabine and irinotecan, given every 2 weeks, as first-line treatment of MCRC is an active regimen with a manageable toxicity profile, even in older patients.

Bevacizumab in Combination with Capecitabine plus Irinotecan as First-Line Therapy in Metastatic Colorectal Cancer: A Pooled Analysis of 2 Phase II Trials

“…The pooled sample from the 2 studies consisted of 99 patients in total, 53 patients from the previously mentioned XELIRI phase II study [7] and 46 patients from the XELIRI plus bevacizumab phase II study [8] (intent-to-treat populations). Baseline characteristics were similar in both studies, except for the male:female ratio, which was significantly different in the XELIRI group (table 1).…”

“…The study details for both phase II trials, one of which involved XELIRI [7] and the other XELIRI plus bevacizumab [8], have been described previously. In brief, patients aged 18-75 years with previously untreated, measurable, histologically confirmed, metastatic or advanced CRC, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate bone marrow, hepatic, and renal function were enrolled.…”

“…Bevacizumab 5 mg/kg was given as a 30- to 90-min intravenous infusion before irinotecan on day 1 to patients in one study [8]. In the other study, the starting doses of irinotecan and capecitabine were reduced to 140 mg/m 2 and 750 mg/m 2 twice daily, respectively, in patients ≥ 65 years old [7]. In both studies, evaluation of disease status, according to Response Evaluation Criteria in Solid Tumors (version 1.0) [9], was carried out every 8 weeks until disease progression, death, or loss to follow-up.…”

“…However, no studies directly comparing XELIRI with XELIRI plus bevacizumab have been published to date. In order to compare 2-weekly XELIRI with XELIRI plus bevacizumab in the first-line treatment of patients with mCRC in the absence of prospective comparative studies, we performed a retrospective pooled analysis of efficacy and safety data from 2 phase II studies investigating the efficacy and tolerability of 2-weekly XELIRI regimens [7,8]. …”

Cantharidin Combined with Chemotherapy for Chinese Patients with Metastatic Colorectal Cancer

“…To reduce the side effect of diarrhea, a 2-week XELIRI regimen was tried recently. The 2-week regimen (irinotecan on day 1, capecitabine on days 2-8 or days 1-5 and 8-12) exhibited promising activity (TTP,(8)(9)(10)OS,(15)(16)(17)(18)(19) with improved tolerability (grade 3/4 diarrhea, 8.1-15.0%) (Garcia-Alfonso et al, 2009), but an increased rate of severe diarrhea was noted in elderly patients, which resulted in dose reduction (GarciaAlfonso et al, 2009). So, in this field no standard regimen is available.…”