Irinotecan monotherapy as third-line or later treatment in advanced gastric cancer

Abstract

Irinotecan monotherapy was relatively safely performed as salvage-line treatment for AGC in Japanese clinical practice. Careful patient selection and intensive modification of the dose of irinotecan might possibly be associated with favorable survival.

Association between UGT1A1 gene polymorphism and safety and efficacy of irinotecan monotherapy as the third-line treatment for advanced gastric cancer

“…Furthermore, this study showed that survival benefits of third-line irinotecan was lower in patients with the Homo/ DH genotype UGT1A1 polymorphism compared with patients with the WT and SH polymorphisms (OS: 2.8 versus 6.9 and 6.3 months, respectively). The median OS in the WT and SH groups was similar to those reported in previous retrospective studies of third-or later-line treatment with irinotecan ranging 4.0-6.6 months [20][21][22]. However, the median OS in the Homo/DH group seemed as short as those of best supportive care in pivotal phase III studies (2.4, 3.6, 3.8, 4.1, and 4.3 months in AIO study [4], COUGAR-02 study [5], Korean study [6], ONO-4538-12 study [9], and GRANITE-1 [23] study, respectively).…”

<p>Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells</p>

“…[6][7][8] It has also been applied to gastric cancer treatment. 9,10 Nonetheless, the therapeutic effect of IRI is still hampered by acquired chemotherapy resistance. 11 Therefore, it is necessary to devise a promising and safe treatment regimen to overcome drug resistance and reduce drug side effects in gastric cancer.…”

Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil in advanced gastric cancer refractory or intolerant to fluoropyrimidines, platinum, taxanes, and irinotecan

“…As for treatment lines, 34% of patients in the apatinib group and 79% of patients in the nivolumab group were treated as fourth-or further-line therapy. In recent retrospective studies, the ORR and median PFS of irinotecan and ramucirumab monotherapy as third-or further-treatment line have been reported to be 3-18 and 7.7%, and 2.2-3.8 and 2.1 months, respectively [17][18][19]31]. In the present study, patients were expected to have worse outcomes than the patient population in the phase-III studies of apatinib and nivolumab (PS 2 or 3 in 28% and third or more lines of therapy fail in 76%), but comparable survival and a better response rate were achieved than those of apatinib, nivolumab, irinotecan, and ramucirumab.…”

“…In a Japanese phase-III study that compared irinotecan with paclitaxel in the second-line setting, 75% of the patients in the paclitaxel arm received irinotecan as a third-line treatment, resulting in longer OS than that in previous studies [16]. Moreover, three Japanese retrospective studies demonstrated that irinotecan monotherapy has modest activity as third-line chemotherapy for AGC [17][18][19]. Based on these results, apatinib, nivolumab, or irinotecan monotherapy is a reasonable therapeutic option for selected patients in the third-or later-line setting.…”