To the best of our knowledge, this is the first study to compare TC and TP regimens in patients with LA-ESCC for NCRT. In the present retrospective study, we aimed to evaluate whether the TC regimen was superior to the TP regimen, which is a better chemotherapy regimen for NCRT in patients with LA-ESCC. Herein, we evaluated AEs and treatment-related effects of TC and TP regimens. The results suggest that either hematologic or non-hematologic AEs occurred less frequently in the TC group during NCRT. We noted no significant differences in postoperative complications. In addition, the incidence of pathological findings (including pCR and R0 resection rate) and survival outcomes were similar in both regimens. The TC regimen exhibits low toxicity and comparable efficacy.
The weekly TC regimen has afforded excellent efficacy in the CROSS study [10]. Since then, the carboplatin plan has been widely accepted and recommended by the National Comprehensive Cancer Network guidelines as the standard chemotherapy regimen for concurrent chemoradiotherapy, including neoadjuvant and definitive therapy. Regarding safety, patients in the TC group experienced mild AEs in the present study, with fewer grade 3 AEs and higher hematologic and gastrointestinal toxic effects than those in the TP group. However, toxic effects in the present study were more severe than those in the CROSS study, especially hematologic toxic effects (33.8% for over grade 3 leukopenia), which could be attributed to higher doses and fewer cycles of chemotherapy regimens. Herein, all patients who received the triweekly TC regimen completed two cycles of chemotherapy on an in-patient basis, which provided better management of the patient’s condition and AEs over a short period. Moreover, fewer chemotherapy cycles can result in larger financial benefits. However, patients who underwent weekly regimens mostly underwent outpatient chemotherapy. Conversely, a triweekly regimen is worthy of clinical consideration and application.
The nutritional status of patients with esophageal cancer tends to be poor, and malnutrition can lead to poor prognosis and death [18, 19]. Gastrointestinal AEs is a major factor in the aggravation of poor undernutrition condition in the treatment of patients with LA-ESCC. Thus, the management of adverse reactions in the alimentary tract is critical during chemoradiotherapy. Neoadjuvant therapy-related AEs can also have serious consequences, including failure to complete chemotherapy cycles, high risk of failure to progress to surgical resection, and poor OS [20–23]. In our study, the TP regmen shows higher rates of nausea (p = 0.038) and anorexia ( p = 0.047), which result in a number of potential risk factors for malnutrition and poor prognosis. Therefore, we recommend the TC regimen as a superior alternative for NCRT.
Although the superiority of the TP regimen has been previously reported [11, 24, 25], a recent RCT has shown that TP does not afford better OS than TC regimens for definitive chemoradiation in patients with LA-ESCC [26]. However, higher rates of hematologic and gastrointestinal toxic effects were observed in the cisplatin group than in the carboplatin group. Similarly, another study has revealed that the TP regimen did not confer a survival advantage over other platinum-based therapies combined with paclitaxel in definitive chemoradiation [27]. Our findings support those reported in previous reports, and there was no significant difference in OS and PFS between the TC and TP regimens.
The limitations of the present study need to be addressed. First, this was a retrospective cohort study, with potential selection bias when compared with prospective randomized controlled studies. We attempted to match the two groups to eliminate the influence of bias and found that baseline characteristics were well balanced, implying that some bias may exist but remains insignificant. In addition, the follow-up durations were relatively short (mean follow-up duration, 26.9 months), and the median OS was not reached. Moreover, in our cohort, episodes of AEs were under-reported, given that this information was not prospectively gathered, and these mild events would not have warranted intervention or a change in treatment. A larger study comparing TC and TP regimens for NCRT in LA-ESCC is warranted.