DISCUSSION
Esophageal carcinoma, malignancy, ESCC, failure of platinum‐based
ESOPHAGEAL CARCINOMA, SOLID TUMOR, SECONDARY, COLORECTAL CANCERS, ESOPHAGEAL CARCINOMA
Esophageal carcinoma is a highly fatal malignancy in China, 95% of which are ESCC. Most patients are in advanced or metastatic stage at the time of diagnosis, and the prognosis is poor. ESCC is a different solid tumor from esophageal and esophagogastric junction adenocarcinoma with respect to biological and geographic distribution despite sharing the same anatomical location.Until now, apart from immune checkpoint inhibitors, there is currently no universally accepted alternative treatment regimen for advanced ESCC.Irinotecan, a topoisomerase I inhibitor, has shown antitumor activity in the treatment of gastric, lung, cervical, and colorectal cancers. As irinotecan monotherapy has low ORR of 10%–15% in the treatment of cisplatin refractory esophageal carcinoma, more and more studies have explored irinotecan‐based regimens to get better clinical efficacy recently.In a retrospective study by Wang et al., a group of 27 advanced ESCC patients were treated with a combination of irinotecan and fluorouracil‐based regimens after the initial failure of platinum‐based treatment. The median PFS and OS for the patients were 4.8 and 10.5 months, respectively.Raltitrexed is a new generation anti‐metabolic cytotoxic drug that is similar to 5‐Fu, S‐1 or capecitabine. It was developed and marketed in the United Kingdom in 1996, while approved for use in China in 2010. A water‐soluble antifolate drug, based on quinazolone, is transported effectively into cells by the reduced folate carrier (RFC). The drug undergoes a significant polyglutamate process through the folylpolyglutamate synthase once inside the cells. Polyglutamation makes the drug over 100 times more active in inhibition and extends its retention time within cells.Recently, raltitrexed has been applied to treat patients with esophageal carcinoma. A prospective study conducted by Sun et al. discovered that concurrent chemoradiotherapy based on raltitrexed/cisplatin was a successful treatment method for ESCC that is locally advanced.Our study aimed to assess the effectiveness and secureness of using irinotecan and raltitrexed as second‐line and subsequent treatments for ESCC patients in the advanced stage. We found no difference in ORR between the two groups, but the subgroup analysis found that in the second‐line treatment group, the DCR of the experimental group was better than that of the control group. We found that PFS and OS of irinotecan combined with raltitrexed treatment was better than that of irinotecan monotherapy, there was statistical significance between two groups. In the stratified analysis, PFS and OS of the two groups were different (median PFS 3.9 m vs. 4.6 m, OS 6.95 m vs. 8.5 m) in the second‐line treatment, but there was no significant difference in the third‐line and beyond treatment. The results of our research showed fluorouracil combined therapy and paclitaxel+platinum therapy had no effect on the subsequent PFS and OS. However, both regimen therapy which was used reduced the subsequent PFS and OS. It indicated that these two regimens did not produce secondary resistance to irinotecan or raltitrexed, and did not affect subsequent use. It also indicated that fluorouracil and raltitrexed, although both belong to antimetabolites, did not produce cross‐resistance. However, if both treatment options were used, PFS and OS will be much worse indicating that it is easier to develop drug resistance after multiline chemotherapy, which affects the efficacy.Dr Chen