Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival

Abstract

Background The aim of this study was to evaluate the activity and safety of the combination chemotherapy of 5-fluorouracil (5-FU), leucovorin, and irinotecan (FOLFIRI regimen) after failure of fluoropyrimidine, platinum, and taxane in gastric cancer (GC) and to evaluate the prognostic factors for survival. Methods Patients received biweekly FOLFIRI chemotherapy as third-line treatment. The FOLFIRI-1 consisted of irinotecan (180 mg/m 2 in a 2-h infusion) on day 1, and then leucovorin (200 mg/m 2 in a 2-h infusion) and 5-FU (a 400 mg/m 2 bolus, followed by 600 mg/m 2 in a 22-h continuous infusion) on days 1 and 2. FOLFIRI-2 consisted of irinotecan (180 mg/m 2 in a 2-h infusion) on day 1, and then leucovorin (400 mg/m 2 in a 2-h infusion) and 5-FU (a 400 mg/m 2 bolus, followed by 2400 mg/m 2 in a 46-h continuous infusion) on day 1. Results A total of 158 patients were included. The overall response rate was 9.6 % in patients with measurable lesions. The median progression-free survival (PFS) and overall survival (OS) were 2.1 months [95 % confidence interval (CI), 1.7-2.5] and 5.6 months (95 % CI, 4.7-6.5), respectively. The major grade 3/4 toxicity was myelosuppression (36.7 %). Good performance status (PS), fewer metastatic sites, and longer duration from the first-line to third-line chemotherapy were independent prognostic factors affecting both PFS and OS. Conclusions The FOLFIRI regimen showed antitumor activity and tolerable toxicity profiles against advanced GC in the third-line setting. Patients with good PS, fewer metastatic sites and longer previous treatment duration might have the maximal benefit from third-line chemotherapy.

Third-Line Chemotherapy with Irinotecan plus 5-Fluorouracil in Caucasian Metastatic Gastric Cancer Patients

“…Our data suggest that also selected Caucasian patients with heavily pretreated disease may derive some benefit from third-line FOLFIRI without excessive toxicities. In particular, almost 1 out of 2 patients experienced disease control in our series, and this is in line with the results reported by Kang et al [10] in a larger Asian population. Moreover, results in terms of both PFS and OS are similar to those achieved in other series, suggesting that some mGC patients may still retain a chemosensitive disease even after two lines of CT.…”

“…The combination of irinotecan and 5-fluorouracil is a manageable regimen, which has been proved an acceptable option in Asian patients with mGC who progressed after two lines of standard regimens [10]. Our data suggest that also selected Caucasian patients with heavily pretreated disease may derive some benefit from third-line FOLFIRI without excessive toxicities.…”

“…Evaluated parameters were identified on the basis of previous reports with second-line or third-line CT [5,6,8,10], i.e., ECOG PS, age, response and PFS with first-line and second-line CT, and time interval from the start of first-line to the start of third-line CT. Continuous variables (first-line and second-line PFS and time from first-line to third-line therapy) were dichotomized according to the median values reported in the cohort.…”

“…The most commonly studied third-line schedules include taxanes and irinotecan as single agents or combinations and have been mostly evaluated in retrospective series. Kang et al [10] evaluated two different FOLFIRI (combination of 5-fluorouracil/folinic acid and irinotecan) schedules (with a different 5-fluorouracil infusion duration) in the so far largest trial including 158 patients who progressed after fluoropyrimidine, platinum, and taxanes. The authors reported a disease control rate of 37.7%, with a median PFS and OS of 2.1 and 5.6 months, respectively, and a favorable safety profile.…”

Irinotecan monotherapy as third-line treatment for advanced gastric cancer refractory to fluoropyrimidines, platinum, and taxanes

“…The median PFS and OS were 3.5 and 6.6 months, respectively, and the overall RR was 23.2%. In another study by Kang et al using irinotecan combined with 5-fluorouracil and leucovorin as third-line therapy in 158 patients, the median PFS and OS were 2.1 and 5.6 months, respectively, and the overall RR was 9.6% [24]. The present study demonstrates that the RR and DCR were as low as 3% and 22%, respectively, and median OS was 4.0 months (95% CI, 2.5-5.5) in 52 patients who were refractory or intolerant to previous treatment with fluoropyrimidines, platinum, and taxanes.…”