Recent advancements in esophageal cancer treatment in Japan

Abstract

The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. Some correction was made in the depth of tumor invasion to be consistent with the TNM classification by the Union for International Cancer Control (UICC). With regard to surgery, short‐term safety and long‐term effectiveness under thoracotomy/video‐assisted thoracoscopic surgery are expected to be proven by the Japan Clinical Oncology Group (JCOG)1409 study. Results of nutritional management and countermeasures for adverse events not only during the perioperative period but also during EC chemotherapy were reported. From now on, the pursuit of low invasiveness and radicality is desired. Esophageal surgery is also expected to be safe at all institutions. To determine the optimal modality of preoperative treatment and a novel chemo(radio)therapy regimen for patients with distant metastasis, the results of the ongoing JCOG1109 and 0807 studies are being released. The effect of the addition of molecular targeted drugs on chemotherapy and concurrent chemoradiation has not yet improved overall survival. Immune checkpoint inhibitor drugs could offer a potential new treatment approach for patients with treatment‐refractory advanced squamous cell carcinoma (SCC). The Cancer Genome Atlas Research Network reported the results of a comprehensive genome analysis and molecular analysis of SCC and adenocarcinoma of the esophagus. Further differentiation of SCC and adenocarcinoma by molecular characterization analysis may be useful for the development of clinical trials and targeted drug therapies as precision medicine. The era of ultimate minimally invasive surgery and personalized treatment has begun. Large, prospective studies will be required to confirm the value of these advancements.

Phase II Trial of 5-Fluorouracil, Docetaxel, and Nedaplatin (UDON) Combination Therapy for Recurrent or Metastatic Esophageal Cancer

“…In the present study, the efficacy and safety of the UDON regimen was evaluated as first-line treatment for Japanese patients with advanced or recurrent esophageal cancer (all of whom had squamous cell carcinoma). Consistent with the results of a previous phase I study [1], a high antitumor activity of UDON was found, with an overall response rate (RR) of 72.7%, which is likely equivalent to that for 3-or 4-weekly DCF (docetaxel, cisplatin, and 5-FU) [2] and possibly higher than that for weekly [3] or 2-weekly DCF [4]. Spider plot analysis revealed a rapid response in 11 of the 16 patients showing a partial response (PR), with these individuals achieving tumor shrinkage of ≥30% after one cycle of UDON chemotherapy.…”

“…The median PFS was 6.0 months (range, 0.9 months to not reached), and the median OS was 11.2 months (range, 4.0 months to not reached). The high antitumor efficacy of UDON was also reflected in survival, with a median PFS and OS of 6.0 and 11.2 months, respectively, values that are again similar to those for DCF , which has yielded a median PFS and OS of 5.8–7.0 months and 11.1–13.0 months, respectively.…”

“…The most frequent severe nonhematologic toxicities in the present study were lung infection and hyponatremia, each with an incidence of 13.0%, followed by mucosal inflammation with an incidence of 8.7%, and then anorexia, nausea, and fatigue with an incidence of 4.3%. For DCF regimens, the most frequent nonhematologic toxicities of grade ≥ 3 (nausea, anorexia, and hyponatremia) were observed in 10%-30% of patients [2]. The lower nonhematologic toxicity of UDON versus DCF is likely attributable to the substitution of nedaplatin for cisplatin, as suggested by a recent phase III study comparing concurrent chemoradiotherapy with nedaplatin versus that with cisplatin in patients with nasopharyngeal carcinoma of stage II-IVB, with the frequency of vomiting, nausea, and anorexia of grade 3 or 4 being significantly higher in the cisplatin arm [5].…”

Significant association between 53 BP1 expression and grade of intraepithelial neoplasia of esophagus: Alteration during esophageal carcinogenesis

“…Further studies are required to elucidate the differences in 53 BP1 expression in non-neoplastic lesions between healthy subjects and patients with SCC. It has been suggested that HG-IN, as well as CIS, should be subjected to endoscopic treatment [5]. Furthermore, according to the most recent Japanese guideline on esophageal carcinoma, HG-IN is histologically defined as a CIS [5].…”

“…When the full thickness of the epithelium is involved, it is classified as carcinoma in situ (CIS). HG-IN, CIS, and early SCC limited to the lamina propria are suitable for endoscopic treatment [4,5]. As the prognosis of advanced esophageal SCC is poor, it is of clinical interest to detect lesions suitable for treatment during the early phase.…”