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Introduction Local recurrence (LR) is clinical challenge in the treatment of esophageal squamous cell carcinoma (ESCC). The current study aimed to determine the optimal re-irradiation dose for local recurrent esophageal squamous cell carcinoma (LRESCC) following radical (chemo) radiotherapy. Methods We retrospectively analyzed 125 patients with LRESCC after receiving initial radiotherapy. For radiotherapy treatment, 58 patients were assigned to low-dose (LD) group (50–54 Gy) and 67 were assigned to the high-dose (HD) group (55–60 Gy). The response rate (complete + partial response), 1-, 2- and 3-year survival rate, and toxicity were recorded. We then analyzed the impact of different radiotherapy doses and combination chemotherapy on the survival of patients with LRESCC. Results After re-irradiation, the 1-, 2- and 3-year survival rates in the LD and HD groups were 48.3%, 24.1% and 10.3% and 61.2%, 34.3% and 19.4% in the HD group, respectively, and the difference in overall survival rate between the two groups were significant (P P Conclusion Higher re-irradiation dose (55–60 Gy) can improve the long-term survival of patients with LRESCC after radiotherapy, with tolerable toxicity.

Squamous cell carcinoma antigen (SCC-Ag) is a widely used tumor marker of SCC. However, the clinical significance of serum SCC-Ag levels in recurrent esophageal SCC (ESCC) remains unclear. This study aimed to investigate the clinical relevance of serum SCC-Ag levels in patients with recurrent ESCC after surgery. This study retrospectively analyzed 208 patients who experienced recurrence after curative resection for ESCC. Serum SCC-Ag levels at the time of recurrence were collected from the patients’ records. The patients were classified into tertiles based on the serum SCC-Ag values (low, middle, and high), and the clinical characteristics and outcomes were compared among the groups. Significant differences in sex (p = 0.001), pathologic T (p = 0.034), and N stages of primary cancer (p = 0.015) were observed among the groups. Although the recurrence patterns did not differ significantly, a high SCC-Ag was significantly associated with multiple recurrences (p = 0.019). The high-SCC-Ag group patients demonstrated a shorter time to recurrence than the other groups (p = 0.044). The SCC-Ag levels were significantly associated with overall survival after recurrence (p = 0.036). Multivariate analysis showed that serum SCC-Ag value at recurrence was an independent poor prognosticator (p = 0.031). Elevated serum SCC-Ag levels at recurrence were significantly associated with a reduced time to recurrence, multiple recurrences, and a poor prognosis after recurrence. An alternative to the current standard treatment is required to improve the outcome for patients with high serum SCC-Ag levels at recurrence.

Although radical esophagectomy with multifield lymph node dissection is a promising treatment to achieve long-term survival for resectable esophageal cancer, survival after postoperative recurrence remains poor. To select the optimal treatment for patients with recurrent esophageal cancer, simple, objective indicators for predicting of long-term outcomes are needed. We conducted a single-institution, retrospective cohort study between 2004 and 2019, wherein 586 patients underwent transthoracic esophagectomy for primary esophageal squamous cell carcinoma. Of these, 133 patients with postoperative recurrence were included in this analysis. Several predictors of survival after recurrence were investigated. Among all patients, the 1- and 3-year survival rates after recurrence were 48.0% and 23.1%, respectively. On multivariate analysis, the neutrophil to lymphocyte ratio (NLR) at recurrence was identified as a significant predictor of death after recurrence (hazard ratio 1.061; 95% confidence interval 1.002–1.125; p = 0.043). Time-dependent receiver operating characteristics curves showed that the area under the curve value of the NLR at recurrence was superior to the modified Glasgow Prognostic Score at recurrence in all terms. To simulate the clinical decision process, we set the cut-off NLR at recurrence for survival using survival classification and regression tree (CART) and defined the optimal cut-off value as 3.374. NLR at recurrence was a significant indicator of survival after recurrence in patients with recurrent esophageal cancer. CART analysis was used to determine the optimal cut-off value for the prediction of survival, allowing the NLR to be used clinically to facilitate decision making.

Background The effectiveness of treatments for recurrent esophageal squamous cell carcinoma (ESCC), particularly chemotherapy and chemoradiotherapy (CRT), remains unclear in patients who have previously been administered the same drugs during neoadjuvant chemotherapy. Methods In this retrospective study, 117 patients with recurrent thoracic ESCCs who had undergone curative resection were included. Patients were divided into two groups based on presurgical treatment: no presurgical treatment (n = 74), and neoadjuvant chemotherapy (n = 43). Prognosis after recurrence was analyzed differently in the group of patients who received CRT and chemotherapy for a recurrent site because of differences in recurrence patterns. Results There were no differences in patterns and times to recurrence between the patients who underwent each presurgical treatment. For treatment of recurrence, CRT was administered to 66 patients, chemotherapy to 32, surgical resection to 5, and best supportive care to 14. In patients who underwent CRT for local recurrence, the survival rates of those administered neoadjuvant chemotherapy were similar to those who did not receive any presurgical treatment (P = 0.706). In patients who underwent chemotherapy for distant metastasis, the survival rates of those administered neoadjuvant chemotherapy were worse than in those who did not receive any presurgical treatment (P = 0.028). Conclusions The effects of CRT for recurrent cancers are not influenced by neoadjuvant chemotherapy, even when using the same anticancer agent. Chemotherapy is an acceptable treatment for patients who do not receive presurgical treatment.

Background In Japan, standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC) includes preoperative chemotherapy with fluorouracil plus cisplatin followed by esophagectomy. However, its efficacy is unclear in patients with recurrent disease with Method We retrospectively evaluated the efficacy of fluorouracil plus platinum in patients with recurrent ESCC who received preoperative chemotherapy followed by curative esophagectomy. Results Among 105 patients with recurrent ESCC after preoperative chemotherapy followed by esophagectomy, a total of 55 patients received fluorouracil plus platinum for recurrent disease. Patients with a CFI n = 20) had significantly shorter overall survival (OS) (median, 7.1 vs 14.5 months, P = 0.008) compared with those with a CFI ≥ 6 months (n = 35). Multivariate analysis showed that OS was worse in patients with a CFI P = 0.001). Conclusion Fluorouracil plus platinum was ineffective for recurrent ESCC in patients with a CFI

Background Several studies have reported the efficacy of resection for recurrent lesions. However, they involved a limited number of subjects. This study aimed to identify a subset of patients who benefit from surgical resection of recurrent lesions after curative esophagectomy for esophageal squamous cell carcinoma. Methods Clinicopathological features of 186 patients with esophageal squamous cell carcinoma who underwent surgical treatment for postoperative recurrent lesions at 37 accredited institutions of the Japanese Esophageal Society were evaluated. Results The most common recurrence site was the lymph node (106 cases; 58.6%), followed by the lung (40 cases; 22.1%). Univariate analyses revealed that pN 0–1 at esophagectomy (P = 0.0348), recurrence-free interval of ≥ 550 days (P = 0.0306), R0 resection (P P = 0.0472) were associated with better overall survival after surgical resection. According to multivariate analyses, pN 0–1 (P = 0.0146), lung metastasis (P = 0.0274), recurrence-free interval after curative esophagectomy of ≥ 550 days (P = 0.0266), R0 resection (P = 0.0009), and absence of severe complications after resection for recurrent lesions (Clavien–Dindo grade P = 0.0420) were independent predictive factors for better overall survival. Conclusions Surgical resection of recurrent esophageal squamous cell carcinoma lesions is a useful option, especially for cases involving lower pN stage, lung metastasis, long recurrence-free intervals after esophagectomy, and technically resectable lesions. Surgical risks should be minimized as much as possible.

The aim of this study was to confirm prognostic factors for salvage esophagectomy for remnant or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy. We retrospectively analyzed clinicopathological backgrounds of 50 patients who underwent salvage esophagectomy between April 2005 and January 2016. Salvage esophagectomy comprised 40 three-incision esophagectomies, two transhiatal esophagectomies and eight pharyngolaryngoesophagectomies. Independent prognostic factors for overall survival were assessed using Cox regression analysis of the factors. Salvage esophagectomy remains a highly invasive surgery and correlated with a higher incidence of all morbidities of Clavien–Dindo classification (CDc) ≥II, severe morbidities of CDc ≥ IIIb, any pulmonary morbidities and chylorrhea, compared with those in patients without preoperative definitive chemoradiotherapy. Cox regression analysis suggested that R0 resection (hazard ratio [HR] 6.39; 95% confidence interval [CI] 2.03–9.68, P = 0.002), absence of severe complications (HR 4.97; 95% CI 1.70–14.81, P = 0.004) and early pStage (0–II) (HR 3.42; 95% CI 1.24–10.12, P = 0.018) were independent prognostic factors for salvage esophagectomy. Salvage esophagectomy remains correlated with a high incidence of postoperative complications. Avoiding non-curative surgery and reducing the incidence of severe postoperative complications are important if patients are to receive prognostic benefit of this highly invasive surgery.

Lessons Learned Weekly treatment with 5-fluorouracil and cisplatin, concurrent with radiotherapy, achieved promising response rates in patients with postoperative recurrent esophageal squamous cell carcinoma. Superior toxicity results were also found. Background Concurrent chemoradiotherapy (CCRT) is one of the treatment strategies for patients with esophageal squamous cell carcinoma (ESCC) with postoperative locoregional recurrence. However, the once every 3 weeks chemotherapy regimen causes a high incidence of toxicity. The aim of this study was to evaluate the efficacy and toxicity of weekly 5-fluorouracil (5-FU) and cisplatin concurrent with radiotherapy in postoperative locoregional recurrent ESCC. Materials and Methods Patients received four weekly chemotherapy cycles of cisplatin (25 mg/m2, day 1) plus 5-FU (1,176 mg/m2, day 1–3), and concurrent with radiotherapy (50.4–60 Gy). The primary endpoint was objective response rate (ORR). Secondary objectives were toxicity, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results Between January 2013 and December 2015, 48 patients were enrolled. The ORR was 68.8% (12 patients with complete response, 21 patients with partial response), with DCR 68.8%. No treatment-related grade 4 adverse events occurred. Grade 3 hematologic toxicities were observed in eight (17%) patients. Grade 3 vomiting or esophagitis occurred in four (8%) patients each. The median PFS and OS were 13.94 months (95% confidence interval [CI], 0.75–51.05) and 27.43 months (95% CI, 5.278–49.58; Fig. 1). Conclusion Weekly 5-FU and cisplatin concurrent with radiotherapy achieved a promising response rate and improved toxicity in patients with postoperative locoregional recurrent ESCC.

Background Re-irradiation (re-RT) has the active effect of relieving clinical symptoms and prolonging the survival of patients with recurrent esophageal squamous cell carcinoma (ESCC). However, the optimal re-RT dose is still uncertain. Here, we analyzed the prognostic factors associated with survival and explored the optimal re-RT dose for patients with recurrent ESCC following definitive radiotherapy. Patients and methods The data of 47 patients with recurrent ESCC who were retreated between 2010 and 2014 were retrospectively analyzed. All patients received a radiation dose > 50 Gy during the primary treatment. The median time to recurrence after primary radiotherapy was 26 months (range 6–120 months). All patients had in-field recurrence in the esophagus. Recurrence within the local site was observed in 37 patients (78.7%), and recurrence in both the local site and regional nodes were observed in 10 patients (21.3%). All patients received 3D conformal re-RT with a median dose of 58 Gy (range 26–64 Gy). Chemotherapy was sequentially used in 27.7% of the patients. Survival curves were constructed according to the Kaplan-Meier method and were compared by log-rank tests. The factors predictive of survival were identified with univariate and multivariate analyses. Results Dysphagia relief after re-RT was achieved in 20 of the 35 symptomatic patients (57.1%). The median survival time (MST) of all patients was 17 months, and the 1-, 2-, 3- and 5-year overall survival (OS) rates were 72.3, 25.5, 17.0 and 2.1%, respectively. In the univariate analysis, an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0–1 (P = 0.014), recurrence at the local site (P = 0.048), time to recurrence ≥24 months (P = 0.006) and re-RT dose ≥50 Gy (P P = 0.007). Severe complications were observed in 7 patients, two of whom received a re-RT dose > 60 Gy. Conclusion Our results demonstrated that patients with recurrent ESCC following definitive radiotherapy had unfavorable OS. Re-RT could be considered a feasible and effective treatment modality. A re-RT dose > 50 Gy could improve the survival outcomes, and a dose > 60 Gy should be administered with caution due to the risk of severe complications.

Introduction: Re-irradiation after radiotherapy is a common treatment for locally recurrent esophageal cancer. However, the side effects of re-irradiation are serious. The most serious adverse reactions of re-irradiation include esophageal perforation and hemorrhage caused by esophageal perforation. Studies have shown that pulsed low-dose rate radiotherapy (PLDR) induces a hypersensitivity effect on tumor tissue and a hyper-repair effect on normal tissue, which can simultaneously reduce damage on the normal tissue and increase the therapeutic effect on the tumor. The objective of this study is to explore whether PLDR can reduce rate of esophageal perforation and improve efficacy in patients with recurrent esophageal squamous cell carcinoma (ESCC) after radiotherapy. Methods and analysis: This study is a prospective, multi-center, open, single-arm clinical trial designed to enroll 27 patients with locally recurrent ESCC after radiotherapy with or without chemotherapy. Re-irradiation will be performed using intensity modulated radiation therapy in 50 Gy/25 fractions. The strategy of PLDR includes dividing 2 Gy into 10 fractions, and administering each irradiating dose of 20 cGy at an interval of 3 minutes before the next low-dose irradiation. The actual dose rate of administration each time will be 16.67 cGy /minute. The primary endpoint in this study is the rate of esophageal perforation. The secondary endpoints are the objective remission rate, the palliative effect on quality of life and pain, and the time of disease progression. The observation time is 2 years after the end of the study. Trial registration: Clinical trial number: ChiCTR1900020609.

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor (EGFR)‑targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR‑targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE‑1, with or without nimotuzumab, were first evaluated by CCK‑8 assay. Colony formation and apoptosis were used to measure anti‑proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2 phase in vitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P

Background/Aims: We investigated factors affecting the post-recurrence prognosis in order to develop adequate therapeutic guidelines for determining the indication for treatment of recurrent esophageal squamous cell carcinoma (ESCC). Methods: Ninety-three thoracic ESCC patients who developed postoperative recurrence after undergoing curative esophagectomy with 3-field lymphadenectomy at our institute and who received treatment for recurrence were enrolled in this study. Results: A univariate analysis showed that distant organ recurrence, the number of recurrent tumors, the longest diameter of the largest recurrent tumor, the sum of all of the longest diameters of the recurrent tumors, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the post-recurrence prognosis. A multivariate analysis showed that distant organ recurrence, the longest diameter of the largest recurrent tumor, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the prognosis. The patients whose recurrent tumor(s) did not meet all 4 of these factors showed a better prognosis. In contrast, the prognosis of the patients whose recurrent tumor(s) demonstrated all 4 factors was almost the same as that observed in the patients who did not receive any treatment for recurrence. Conclusions: The evaluation of these 4 factors may potentially be used to determine the indication for treatment for recurrence.

The aim of this study was to evaluate the prognostic impact of the prognostic nutritional index (PNI) in patients with recurrent esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed 76 ESCC patients who developed recurrence after curative subtotal esophagectomy at Nara Medical University Hospital between January 2001 and October 2016. The PNI at ESCC recurrence was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (/mm3). The cutoff value of the PNI was set at 45. Multivariate analysis was performed to identify the prognostic factors. The mean PNI was 44.0 ± 5.8, and 42 (55.3%) patients had a PNI

Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first-line chemotherapy regimen for these patients has been the combination of 5-fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line chemotherapy for ESCC have not been clarified. A total of 187 patients with metastatic or recurrent esophageal ESCC treated with CF at the National Cancer Center Hospital between January 2001 and December 2012 were enrolled in the study. The CF regimen comprised cisplatin (80 mg/m2) administered on day 1 and 5-fluorouracil (800 mg/m2) administered continuously on days 1–5, every 4 weeks. Multivariate Cox regression analysis was used to determine the potential prognostic factors. The median age of the patients was 62 (range 34–84) years. Metastasis and recurrence occurred in 116 and 71 of these patients, respectively. The overall response rate was 37.2%, with median progression-free and overall survival times of 4.8 and 10.4 months, respectively. In the multivariate analysis, higher serum C-reactive protein level and lower serum albumin level at the time of CF treatment initiation and number of metastatic sites were identified as independent prognostic factors for survival. The results of this study corroborate previous findings on the efficacy of CF and will aid physicians in clinical decision-making and individual patient risk stratification, as well as in the further development of chemotherapy regimens.

Fluoropyrimidine plus platinum (FP)-based chemotherapy has been widely used as a first-line regimen for advanced or recurrent esophageal cancer, and taxanes have shown efficacy after FP-based chemotherapy, but there is no standard regimen for second-line chemotherapy (SLC). We retrospectively investigated the clinical features of taxane therapy in SLC for esophageal squamous cell carcinoma (ESCC).The selection criteria were pathologically proven ESCC; advanced or recurrent disease previously treated with FP at our hospital; performance status (PS) 0-2; and adequate organ function. Docetaxel (DTX) was administered 3-weekly at 70 mg/m(2). Paclitaxel (PTX) was administered at 100 mg/m(2) weekly for 6 weeks, with 1 week's rest.The analysis covered 163 patients from August 2006 to June 2012. Median age was 64 years (range 37-83: DTX group 132 patients and PTX group 31). Progression-free survival and median overall survival (OS) were 2.3 and 6.1 months, respectively, with PTX and 2.3 and 5.3 months with DTX. Response rates were 20.7 % for PTX and 5.9 % for DTX. The rate of grades 3-4 neutropenia was higher with DTX (32.6 %) than with PTX (16.1 %). Grade 3 febrile neutropenia was seen in 6.1 % of DTX recipients but in no PTX group. According to multivariate analyses of OS, PS 2, number of metastatic sites ≧2, and CRP ≧1 mg/dL were independent predictors of poor prognosis.PTX and DTX were both effective in SLC for ESCC, but their toxicity profiles differed. In terms of febrile neutropenia, PTX seems more appropriate.

Background/Aims: This study documents the clinical efficacy and toxicity of S-1 and paclitaxel (S1/PTX) in patients with unresectable or postoperative recurrent esophageal squamous cell carcinoma (ESCC) who had been previously treated with fluorouracil (5FU), cisplatin, and docetaxel. Methods: Twenty-eight ESCC patients treated using S1/PTX at our institute since 2010 were enrolled in this study. S1 was administered orally at a dose of 80 mg/m2/day from days 1 to 14, and PTX was administered intravenously on days 1 and 8 at a dose of 80-100 mg/m2. Results: A total of 106 cycles (median 2.5 cycles, range 1-12 cycles) were administered. The response rate was 14.8%, including 3 complete responses. The median progression-free survival time was 137 days, and the median overall survival time was 306 days. Severe neutropenia occurred in 13 patients, and 3 showed febrile neutropenia. All non-hematological toxicities were mild, and peripheral nerve paralysis was observed in 2 patients. Conclusion: S1/PTX was found to have tolerable clinical efficacy in terms of the response rate, survival and toxicity in patients with unresectable or postoperative recurrent ESCC who had previously been treated with 5FU, cisplatin, and docetaxel.

The patients with metastatic or recurrent esophageal cancer are incurable. A number of patients who progress after first-line chemotherapy may still be fit for second-line treatment. However, there is no currently established effective and tolerable salvage chemotherapy. We investigated the activity and tolerability of MIC in patients who had failed to prior chemotherapy for metastatic or recurrent esophageal squamous cell carcinoma. MIC (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) was given in day 1 as an outpatient regimen and repeated every 3 weeks. All 32 enrolled patients were male with median age of 57 years. Prior esophagectomy had been performed in 21 patients (65.6%) and 11 patients (34.4%) were metastatic disease at initial diagnosis. Nineteen patients (59.4%) were treated with MIC as second-line chemotherapy. Prior first-line chemotherapy regimens consisted of 5-FU/cisplatin and capecitabine/cisplatin combinations. Overall response rate was 12.5% with no CR, and disease control rate was 37.5%. Grade 3/4 neutropenia was observed in 21 % of patients and grade 3/4 febrile neutropenia was seen in only one patient. There was no treatment-related mortality. Median PFS was 2.0 months (95%CI = 1.4-2.5) and the median OS was 5.2 months (95%CI = 3.3-7.0) with no significant difference between numbers of prior chemotherapy regimen. MIC chemotherapy has modest activity as a salvage regimen with tolerable toxicity, and could be one of the chemotherapy treatment options for patients with advanced or recurrent esophageal squamous cell carcinoma for whom previous chemotherapy has failed.

The combination of 5-fluorouracil (5-FU) and cisplatin (FP) remains the mostly used regimen for metastatic esophageal squamous carcinoma. This phase II study assessed the efficacy and safety of capecitabine/cisplatin (XP) as a first-line chemotherapy in a homogenous cohort of patients with metastatic or recurrent esophageal squamous cell carcinoma.Patients received 60 mg/m(2) of cisplatin intravenously (IV) on day 1 and capecitabine 1,250 mg/m(2)/dose orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until the documented disease progression, unacceptable toxicity, or patient's refusal. Immunohistochemical studies against thymidylate synthase (TS) and thymidine phosphorylase (TP) were performed to seek predictive markers for treatment response.Between December 2003 and March 2006, 45 patients entered the study. All patients had histologically proven squamous cell carcinoma of the esophagus. The overall response rate (ORR) was 57.8% (95% CI, 43.3-72.2) with 0 CR and 26 PRs. The median duration of response in responders was 4.6 months (1.0-15.6 months). With a median follow-up duration of 25.7 months (10.8-42.6 months), the median time to progression was 4.7 months (95% CI, 2.5-7.0) and the median survival time was 11.2 months (95% CI, 8.5-13.9). Common grade 3 or 4 non-hematological adverse events were anorexia (18/191, 9.4%), fatigue (9/191, 4.7%), constipation (6/191, 3.1%), hand-foot syndrome (6/191, 3.1%) and diarrhea (4/191, 2.1%). The most common grade 3 or 4 hematological adverse events were neutropenia (33/191, 17.3%), followed by leucopenia (11/191, 5.8%), anemia (2/191, 1.0%) and thrombocytopenia (1/191, 0.5%). There was no treatment-related death. Neither TS nor TP showed predictive value for treatment response.The XP regimen demonstrated a promising antitumor activity in metastatic esophageal squamous cell carcinoma, which may potentially replace the FP regimen.

This phase II study assessed the efficacy and toxicity profile of a modified weekly irinotecan and cisplatin for chemotherapy-naïve patients with metastatic/recurrent esophageal squamous cell carcinoma (SQCC).The eligibility criteria included histologically confirmed esophageal SQCC, no prior chemotherapy, adequate organ functions and written informed consent. Patients received irinotecan 65 mg/m(2) plus cisplatin 30 mg/m(2) on days 1 and 8, every 3 weeks.Thirty-two patients were assessed for response and toxicity. Ten patients achieved a partial response (31.3%; 95% CI, 16.0-50.0%). With a median follow-up of 19.0 months, median progression-free and overall survival was 4.4 and 9.6 months, respectively, with a 1-year survival rate of 27.4%. Grade (G) 3/4 neutropenia was observed in 50.0% of the patients, which was the most common cause of dose reduction or therapy delay. G3 non-hematologic toxicity included seven (21.9%) asthenias, four (12.5%) diarrheas, and one (3.1%) nausea/vomiting, but no G4 non-hematologic toxicity was observed.This modified weekly irinotecan and cisplatin failed to ameliorate hematologic toxicity and to improve efficacy. However, easy administration and favorable non-hematologic toxicity as well as modest anti-tumor activity against metastatic or recurrent esophageal SQCC can make this regimen a potential treatment option, given the complexity of administration and toxicity of conventional infusional 5-FU and cisplatin.

Background: To evaluate the activity and toxicity of docetaxel in patients with metastatic esophageal cancer. Patients and methods: Eligible patients had histologically confirmed carcinoma of the esophagus with measurable metastatic sites according to Response Evaluation Criteria in Solid Tumors (RECIST). Patients were either chemotherapy-naive or previously treated with one regimen of chemotherapy. Docetaxel 70 mg/m 2 was administered intravenously over 1–2 h, every 21 days. Results: Of 52 patients enrolled in this study, three were excluded because they did not receive docetaxel due to worsening condition after enrollment. Thirty-six patients had received prior platinum-based chemotherapy. The majority of patients (94%) had squamous cell carcinoma. Ten of 49 evaluable patients [20%; 95% confidence interval (CI) 10–34%] showed a partial response. Of the 10 partial responses, six patients had received prior platinum-based chemotherapy. Grade 3 or 4 neutropenia was noted in 43 of 49 patients (88%), and nine of 49 patients (18%) developed febrile neutropenia. Twenty-eight of 49 patients (57%) required lenograstim. Grade 3 anorexia and fatigue occurred in nine (18%) and six (12%) patients, respectively. Median survival time was 8.1 months (95% CI 6.6–11.3) and the 1-year survival rate was 35% (95% CI 21–48%). Conclusions: Docetaxel as a single agent is effective in esophageal cancer, but careful management of neutro

Objectives To date, no second-line chemotherapy regimen for esophageal squamous cell carcinoma (SCC) has been established. This clinical trial aimed to assess the optimum dose of docetaxel plus nedaplatin (cis-diammine-glycolate platinum) as second-line chemotherapy. Methods Patients with metastatic or recurrent esophageal SCC after treatment with cisplatin plus 5-fluorouracil received docetaxel (50 or 60 mg/m) plus nedaplatin (70 mg/m²) on day 1 every 4 weeks. The recommended dose was based on dose-limiting toxicities defined during the first cycle. Results From February 2009 to November 2011, 9 patients were enrolled in the study. Their median age was 62 years (range, 58 to 72 y). Six patients had undergone radiotherapy and 4 had undergone surgical resection of primary lesions. Dose-limiting toxicities were observed in 2 patients at dose level 1 (60 mg/m² docetaxel, 70 mg/m² nedaplatin) but not at dose level 0 (50 mg/m² docetaxel, 70 mg/m nedaplatin). Thus, the maximum tolerated dose was established at dose level 1. No severe nonhematological toxicity was observed. No patient achieved complete response, but 2 (22%; 95% confidence interval, 0%-49%) achieved partial response and 3 had stable disease. Median progression-free and overall survival times were 2.1 and 9.5 months, respectively. Conclusions Docetaxel plus nedaplatin chemotherapy seems to be a safe and feasible second-line regimen for the treatment of esophageal SCC. We recommend the administration of 50 mg/m² docetaxel (day 1) plus 70 mg/m² nedaplatin (day 1) every 4 weeks in a phase II study.

Purpose: S-1 is widely used for various cancers. It may be useful for esophageal squamous cell carcinoma (ESCC); however, there are insufficient data. The purpose is to provide results of an analysis of S-1 monotherapy for unresectable and recurrent ESCC. Patients and Methods: Twenty patients with histologically proven ESCC who were previously treated with other chemo(radio)therapies were treated with S-1 alone as second- or third-line chemotherapy. Results: A complete response (CR) was observed in 1 case (5%). A partial response (PR), stable disease (SD), and progressive disease (PD) were seen in 4 (20.0%), 7 (35.0%), and 8 (40.0%) cases, respectively. Two cases (10%) of anemia, 1 case (5%) of leukopenia, 3 cases (15%) of fatigue, and 3 cases (15%) of diarrhea were observed as grade 3 toxicity; however, there were no cases of grade 4 toxicity. The 1-year progression-free survival (PFS) rate was 10.0%, and the median PFS was 100 days. The 1-year overall survival (OS) was 30.5%, and the median OS was 330 days. The 1-year PFS rate in CR/PR/SD and PD was 16.7 and 0%, and the median survival time was 120 and 40 days. Conclusion: S-1 is a promising new drug which can be used as a second- or third-line chemotherapy for ESCC.

Background This phase II study assessed the response rate and toxicity profile of weekly paclitaxel and capecitabine in patients with metastatic or recurrent squamous cell carcinoma of the esophagus (SCCE) Methods Patients with histologically confirmed SCCE were treated with paclitaxel 80 mg/m2 intravenously on days 1 and 8 plus capecitabine 900 mg/m2 orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until disease progression or unacceptable toxicity. Results Between 2006 and 2009, 32 patients were enrolled. Twelve patients were chemotherapy-naïve. Twenty patients had received prior chemotherapy including platinum-based regimens. Patients received a median of 5 cycles of treatment (range, 1-12). The response rate was 75% (95%CI; 50.5~99.5%) in the first-line and 45% (95%CI; 26.9~73.1%) in the second-line. With a median follow-up of 20.7 months, median progression-free survival was 5.2 months (95% CI, 4.0 to 6.4) for all patients and median overall survival (OS) was 11.7 months (95% CI, 5.5 to 18.0) for all patients. The median OS was 14.3 months (95% CI, 10.6 to 18.0) for patients receiving therapy as 1st line and 8.4 months (95% CI, 6.6 to 10.1) for those receiving as 2nd-line therapy. Grade 3/4 neutropenia was observed in 53.3% of the patients, which was the most common cause of dose reduction. G3 non-hematologic toxicity included stomatitis (9.4%), asthenia (6.3%), and hand-foot skin reaction (3.1%). Conclusions Weekly paclitaxel and capecitabine is a highly active and well-tolerated regimen in patients with metastatic or recurrent SCCE in the first-line as well as second-line setting.

This study was performed to determine the feasibility and safety of salvage chemotherapy, using docetaxel and cisplatin in 5-fluorouracil (5-FU) and cisplatin-pretreated esophageal cancer.Patients with metastatic or recurrent esophageal squamous cell carcinoma that had previously been treated with 5-FU and cisplatin chemotherapy or chemoradiotherapy were eligible for this study. Docetaxel (70 mg/m²) and cisplatin (75 mg/m²) were given as a 1-hour intravenous infusion on day 1, and the treatment was repeated every 3 weeks.Thirty-eight male patients were enrolled, and 35 patients were available for evaluation. The median age was 64.5 years; Eastern Cooperative Oncology Group performance status was 0/1/2 = 2/18/18. The median and total numbers of cycles delivered were 3.5 (range, 1-9 cycles) and 162, respectively. One patient (2.6%) achieved complete response, 12 (31.6%) achieved partial response, 12 (31.6%) had stable disease, and 10 (26.3%) had progressive disease. The overall response rate was 34.2% (95% confidence interval, 19.6-51.3). The median progression-free survival and overall survival times were 4.5 ± 1.3 months (95% CI, 4.1-4.9) and 7.4 ± 0.4 months (95% CI, 7.3-7.5), respectively. The main hematological toxicities greater than grade 3 were neutropenia and leucopenia in 20 (52.6%) and 18 patients (47.3%), respectively. Nonhematological toxicities greater than grade 3 included asthenia in 12 patients (31.6%), nausea in 7 patients (18.4%), and peripheral neuropathy in 6 patients (15.8%).Chemotherapy with docetaxel and cisplatin was an effective and feasible treatment following treatment with 5-FU and cisplatin, and would be considered as a salvage option for patients with refractory esophageal cancer.

This study assessed the clinical activity and safety of twice-weekly paclitaxel and cisplatin combined with 5-fluorouracil and leucovorin (TP-HDFL) in patients with recurrent or metastatic esophageal squamous cell carcinoma. The regimen, composed of paclitaxel 35 mg/m 1-h intravenous infusion on days 1, 4, 8 and 11; cisplatin 20 mg/m 2-h intravenous infusion on days 2, 5, 9 and 12; and 5-flourouracil 2000 mg/m and leucovorin 300 mg/m 24-h intravenous infusion on days 5 and 12; repeated every 21 days. Forty-one patients (median age 51), 15 with de-novo metastatic disease and 26 with recurrent disease, were enrolled. Grades 3-4 neutropenia, leukopenia and diarrhea occurred in 37.8, 29.4 and 14.2% of cycles, respectively. One patient died of invasive fungal infection. Three complete responses, 13 partial response and 13 stable diseases were observed. The intent-to-treat response rate was 39.0% (95% confidence interval: 24-54). The median progression-free and overall survival were 6.3 and 8.9 months (range 1-50+), respectively. Twice-weekly TP-HDFL has the activity and toxicity profile similar to the previously reported same three-drug combination for advanced esophageal cancer.

Thirty-nine patients with advanced measurable squamous cell carcinomas were treated with two or more courses of 70 mg cisplatin/m2 on day 1 and 700 mg infused 5-fluorouracil/m2 on days 1-5 every 21 days. The overall response rate was 35.9 (95% confidence limits, 24.8-55.1%). Responses were seen in primary sites in the esophagus of five patients, in the lung of seven, the liver of one and the mediastinal lymph nodes of one. The average response duration was 3.5 (range 1-12) mo for patients who achieved partial response. The average survival time after the first administration was 9.5 mo for patients who responded to the treatment whereas, for those who did not, it was 5.6 mo. The major form of toxicity was myelosuppression and there were six patients with grade 3 toxicity and one with grade 4. The present study was designed to evaluate the effectiveness of combined cisplatin and 5-fluorouracil for advanced squamous cell carcinoma, and the results showed that it had a reasonable effect and might possibly be used as a postoperative chemotherapy because of its mild side effects.

Background: There is an urgent need for an effective second-line chemotherapy regimen after failure of the standard cisplatin and 5-fluorouracil therapy. Patients and Methods: This study investigated the efficacy and toxicity of the combination of docetaxel (30 mg/m2) during a 1-hour infusion, followed by nedaplatin (50 mg/m2) during a 2-hour infusion (both drugs were administered on day 1 as an outpatient regimen and repeated every 2 weeks) as second-line chemotherapy for patients with cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma after surgery. Results: Forty-six of the 48 patients (95.8%) were assessable for response. Partial response was confirmed in 13 of 48 cases yielding a response rate of 27.1% (95% confidence interval [CI], 14.5–39.7%). The median overall time to progression and overall survival was 3.1 months (95% CI, 2.3–3.9 months) and 5.9 months (95% CI, 3.9–7.8 months), respectively. The estimate of overall survival at 12 months was 16.7% (95% CI, 6.1–27.2%). Grade 3 anemia leucopenia, grade 4 anemia leucopenia and neutropenia were detected in only 4 (8.7%), 8 (17.4%), and 9 patients (19.6%), respectively. Conclusions: The combination chemotherapy of docetaxel and nedaplatin in the outpatient setting is well tolerated and useful as second-line chemotherapy for cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma.

Purpose The aim of this study was to evaluate the salvage radiotherapy outcome in patients with local recurrent esophageal cancer after radical radiochemotherapy (RCT). Methods A total of 114 patients with local recurrent esophageal squamous cell carcinoma after initial radical RCT were retrospectively analyzed. Fifty-five (55) patients belonged to the salvage radiotherapy group (SR group) and 59 patients to the non-salvage radiotherapy group (NSR group). Results The median survival time after-recurrence was 4 months in all patients. The 1, 2, 3 year overall survival (OS) rates were 83.6%, 41.8% and 21.8% respectively in the SR group, and 57.6%, 16.9%, and 8.5% in the NSR group. The 6-month and 1-year survival rates after-recurrence were 41.8% and 16.4% respectively in the SR group, and 11.9% and 3.4% respectively in the NSR group. A salvage radiation dose > 50 Gy after initial radical RCT, improved the survival of patients with local recurrent esophageal cancer. Three patients (5.45%) from the SR group showed more than 3-grade radiation pneumonitis. In addition, esophageal fistula/perforation was observed in 11 cases (20.0%) in the SR group and in 8 cases (13.6%) in the NSR group. Conclusions Salvage treatment after definitive RCT may improve the overall survival and survival after-recurrence of patients with local recurrent esophageal cancer.