A phase I study of combination therapy with S-1 and irinotecan (CPT-11) in patients with advanced colorectal cancer

Purpose  The aim of this study was to determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan (CPT-11) plus S-1 in advanced colorectal cancer. Methods  S-1 was administered orally at 80 mg/m² per day for 14 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 80 mg/m² per day, stepping up to 100, 120 or 150 mg/m² per day. Courses were repeated every 4 weeks, unless disease progression or severe toxicities were observed. Results  A total of 21 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 150 mg/m², because 2 of 3 patients developed dose-limiting toxicities such as leukopenia, neutropenia, diarrhea and anorexia. The recommend dose of CPT-11 was set at 120 mg/m². Tumor response rate was 42.8% and median progression-free survival time was 10 months (95% confidential interval, 6.0–14.0 months). Conclusion  A combination of S-1 and CPT-11 showed a good safety profile and can be recommended for further phase II studies in patients with colorectal cancer.     

S-1 plus gemcitabine chemotherapy followed by concurrent radiotherapy and maintenance therapy with S-1 for unresectable pancreatic cancer

AIM: To investigate the feasibility and efficacy of the combination of S-1 with gemcitabine followed by oral S-1 with concurrent radiotherapy (intensity modulated radiotherapy, IMRT) and maintenance therapy with S-1 for locally advanced pancreatic cancer.METHODS: Subjects selected in the study were patients who had unresectable and locally advanced pancreatic cancer without distant metastases, adequate organ and marrow functions, an Eastern Cooperative Oncology Group performance status of 0-1 and no prior anticancer therapy. Initially the subjects received two cycles of chemotherapy, oral administration of S-1 40 mg/m² twice daily from day 1 to day 14 of a 21-d cycle, with 30-min intravenous infusions of gemcitabine 1000 mg/m² on day 1 and day 8. Two weeks after the completion of chemotherapy, S-1 was administered orally with concurrent IMRT. Oral S-1 was administered at a dose of 80 mg/m² per day twice daily from day 1 to day 14 and from day 22 to day 35. Radiation was concurrently delivered at a dose of 50.4 Gy (1.8 Gy/d, 5 times per week, 28 fractions). One month after the completion of chemotherapy and radiotherapy, S-1 was administered orally at a dose of 80 mg/m² per day twice daily for 14 d, followed by a 14-d rest period. This cycle was repeated as maintenance therapy, until unacceptable toxicity occurred or the disease worsened. Thirty-two patients were involved in this study. The median follow-up was 15.6 mo (range: 8.6-32.3 mo).RESULTS: Thirty-two patients completed the scheduled course of chemotherapy, while 30 patients (93.8%) received chemoradiotherapy with two patients ceasing to continue with radiotherapy. The major toxic effects were nausea and leukopenia. There was no grade 4 toxicity or treatment-related death. According to the Response Evaluation Criteria in Solid Tumors criteria, the objective tumor response was partial response in 17 (53.1%) patients, stable disease in 9 (28.1%), and progressive disease in 6 (18.8%). The median overall survival and median progression-free survival were 15.2 mo and 9.3 mo, respectively. The survival rates at 1 year and 2 years were 75% and 34.4%, respectively.CONCLUSION: The combination of S-1 with gemcitabine followed by oral S-1 with IMRT and maintenance therapy with S-1 alone in patients with locally advanced pancreatic cancer may be considered a well-tolerated, promising treatment regimen.     

Effect and safety of anlotinib combined with S-1 for recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy

This study aimed to evaluate the effect and safety of anlotinib combined with S-1 in the treatment of recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy.This study retrospectively reviewed 22 recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy between June 1, 2018 and February 28, 2019. All patients did not previously receive anlotinib or S-1.Of 22 patients, 20 patients had squamous cell cancer. Seventeen patients received at least 2 cycles of anlotinib plus S-1. The objective response rate (ORR) was 35.3%, and the disease control rate (DCR) was 82.4%. The median progression-free survival (PFS) was 3.5 months, and median overall survival (OS) was 5.2 months. In the first-line treatment subgroup, the ORR was 50%, the DCR was 80%, the median PFS was 4.5 months, and the median OS was 5.8 months. In the second-line and above treatment subgroup, the ORR was 14.3%, the DCR was 85.7%, the median PFS was 3.0 months, and the median OS was 3.7 months. The main adverse events (AEs) of anlotinib combined with S-1 were fatigue (58.8%), hypertension (47.1%), hemoptysis (29.4%), anemia (29.4%), nausea (23.5%), liver function damage (23.5%), albuminuria (17.6%), abdominal pain (17.6%), leukopenia (17.6%), neutropenia (11.8%), fever (11.8%), and hand-foot syndrome (11.8%). Grade 3 AEs included nausea (5.9%) and hypertension (5.9%), and no grade 4 or more AEs were reported.Anlotinib combined with S-1 achieved promising disease control and satisfactory survival with tolerable safety in recurrent metastatic esophageal cancer who refused or were intolerant to intravenous chemotherapy.     

Esophageal cancer: definitive chemoradiotherapy for elderly patients

To investigate the efficacy and toxicity of definitive chemoradiotherapy (CRT) for elderly patients with locally advanced esophageal cancer. Twenty‐two patients aged over 75 that performed definitive CRT were retrospectively reviewed. The regimen included concurrent CRT consisting of two cycles of chemotherapy (CTx) of platinum and 5‐fluorouracil, and radiation therapy (RT) of 50–50.4 Gy (actual range: 45.4–71.4 Gy), and additional CTx where possible. Both CTx and RT were reduced in dose and field where necessary. The disease‐free survival rate and the overall survival rate at 3 years were 33.3% ± 11.4% and 25.9% ± 10.8%. Grade 4 leukocytopenia and thrombocytopenia occurred in three (14%) and four (18%) patients. Treatment‐related death was suspected in up to four (18%) patients at the most. Univariate analyses for disease‐free survival showed that neither total radiation dose nor number of total cycles of CTx was significant. The pattern of relapse was predominantly more frequent in the intra‐RT field than outside the RT field. For elderly patients, adverse events are frequent, and decreased organ reserve may cause treatment‐related death. Reduction in CTx dose or RT field, appropriate only for two cycles of CTx, and careful monitoring may help to minimize toxicity. Physicians should not be too afraid of adverse events or be negative about CRT for elderly patients, as long as comorbidities and complications are managed carefully.     

Concurrent chemoradiotherapy with S‐1 and cisplatin in advanced esophageal cancer

How best to manage advanced esophageal cancer remains unresolved, especially in palliative care. Here, in a pilot study, we evaluated the efficacy and safety of concurrent chemoradiotherapy with S‐1 and cisplatin in advanced esophageal cancer. Patients with locally advanced or metastatic squamous cell carcinoma of the esophagus received S‐1 and cisplatin at doses of 70 mg/m²/day for 14 days and 70 mg/m² on day 1, respectively, every 3 weeks. Concurrently, radiotherapy was started at a dose of 200 cGy/day, up to a total of 5400 cGy. After concurrent chemoradiotherapy, additive chemotherapy was repeated up to six cycles. Thirty patients were enrolled in this study; of the 27 in whom efficacy could be evaluated, an objective response rate was seen in 20 (74.1%), including five (18.5%) complete pathologic responses in primary lesions. Improvement of dysphagia was seen in 21 (76%) patients. In patients with stage II or III esophageal cancer, the median progression‐free survival and overall survival were 10.6 ± 0.6 months (95% CI: 9.4–11.8) and 23.0 ± 5.1 months (95% CI: 13.0–32.9), respectively. In patients with stage IV esophageal cancer, the median progression‐free survival and overall survival were 5.4 ± 1.6 months (95% CI: 2.2–8.6) and 11.6 ± 1.6 months (95% CI: 8.4–14.8), respectively. The main hematological toxicity was neutropenia, but no neutropenic fever was observed. The major non‐hematological toxicities were asthenia and vomiting, mostly of grades 1 and 2. Thus, concurrent chemoradiotherapy with S‐1 and cisplatin may be a promising nonsurgical treatment in advanced esophageal cancer.     

Successful treatment of S-1 + CDDP followed by salvage EMR for a case with metastatic Barrett's esophageal cancer

SUMMARY.  A 62-year-old woman with Barrett's esophageal cancer was hospitalized. Abdominal CT confirmed metastases to the liver and lymph nodes, for which surgical excision and radiotherapy were not indicated. We started chemotherapy with a course of daily oral S-1 at a dose of 80 mg/m² for 21 days, with a 2-hour drip of cisplatin at 60 mg/m² on day 8. Breaks of 14 drug-free days were given between courses. After two courses, a repeat CT confirmed that the liver and lymph node metastases had disappeared; after three courses, another CT confirmed that the metastatic foci were still absent, so we judged the disease to be in complete remission. Endoscopy and upper GI series confirmed that the primary tumor was reduced, and endoscopic mucosal resection performed using the strip biopsy method. The excision specimen was well differentiated adenocarcinoma, and mucosal invasion, and the excision stump was negative. After two more courses of S-1 + cisplatin, chemotherapy has been suspended with the patient's consent, and in the 21 months after endoscopic mucosal resection, no recurrence has been observed. This is a rare case of metastatic Barrett's esophageal cancer in which the metastases were eradicated by S-1 + cisplatin, and the primary tumor successfully excised by endoscopic mucosal resection after downstaging.     

Outcomes from chemoradiotherapy for patients with esophageal cancer

Chemoradiotherapy is a widely used alternative treatment to surgical resection in certain patient groups with early esophageal cancer. The aim of this study was to retrospectively assess toxicity and outcome of patients treated with definitive chemoradiotherapy for early esophageal cancer at one institution. A retrospective analysis of all patients treated with chemoradiotherapy between February 2000 and December 2008 at a single tertiary center was performed with documentation of treatment given, toxicities recorded, and follow‐up and outcome data. Sixty‐two patients received chemoradiotherapy for esophageal cancer. There were 20 males and 42 female patients with an average age of 68 years. Histology revealed adenocarcinoma in 28 patients and squamous cell carcinoma in 34 patients. All patients were staged with a computerized tomography scan, endoscopic ultrasound and positron emission tomography scan. Selection criteria for chemoradiotherapy were unfit for surgery, upper esophageal squamous carcinoma, unresectable primary tumor, or patient choice. The majority of the patients received a combination of cisplatin and 5‐fluorouracil chemotherapy with 55 Gy in 25 fractions of radiotherapy. Grade 3 toxicities were recorded in 11% of the patients. Eleven patients suffered from local recurrence and a stent was required in nine patients. Radiation strictures occurred in 10 patients requiring dilation in four. Five patients required a radiologically inserted feeding gastrostomy. The median overall survival was 21 months. Patients with adenocarcinomas and those with squamous cell carcinoma had a similar median survival. Overall survival was 70% at 1 year, 48% at 2 years, and 26% at 3 years. This case series of patients treated with chemoradiation for localized esophageal cancer suggest a generally well‐tolerated treatment with survival rates after chemoradiotherapy comparable with those seen with surgery.     

Assessment of transendoscopic miniature ultrasonic probe for chemoradiotherapy outcome in patients with locally advanced esophageal cancer

Background: Assessment of the response of esophageal cancer to chemoradiotherapy is difficult. We investigated the value of a transendoscopic miniature ultrasonic probe (USP) in assessing response to chemoradiotherapy in patients with locally advanced esophageal cancer. Methods: A total of 33 patients were entered in this prospective study. Response to treatment was evaluated according to World Health Organization criteria. According to the sonographic image, complete response (CR) of the primary lesion was divided into two subcategories: confirmed CR (cCR) and unconfirmed CR (uCR). Results: Initial sonographic criteria for evaluating tumor depth and lymph nodes in the 33 patients before therapy showed two cases of T2N0, four of T3N0, 15 of T3N1, four of T4N0, and eight of T4N1. Following chemoradiotherapy, CR was obtained in 18 (54.5%): seven cCR and 11 uCR. Eleven were partial response (PR) (33.3%), while three were stable disease (SD) and one was progressive disease (PD). High frequency USP (20 MHz) was able to detect tumor disappearance and restoration of the esophageal wall. One‐year survival rates among CR (cCR + uCR), PR and SD + PD were 100%, 70% and 0%, respectively. A significant difference in survival was evident among CR, PR and SD + PD (P < 0.001). Three‐year survival rates between cCR and uCR were 100% and 40%, respectively. A significant difference in survival was evident between cCR and uCR (P < 0.001). In seven cases of uCR, local recurrence and distant metastasis appeared within 1 year, and five died of disease progression. Not one cCR case has relapsed. Conclusion: USP, which can be accomplished with a standard endoscopy, including biopsy, in one procedure, is a useful method for objectively assessing the response to chemoradiotherapy in patients with locally advanced esophageal cancer.     

Results of chemoradiotherapy for stage I esophageal cancer in medically inoperable patients compared with results in operable patients

The purpose of the present study was to evaluate long‐term results of chemoradiotherapy for clinical T1b‐2N0M0 esophageal cancer and to compare outcomes for operable and inoperable patients. Patients with stage I esophageal cancer (Union for International Cancer Control [UICC] 2009), excluding patients with cT1a esophageal cancer, were studied. All patients had histologically proven squamous cell carcinoma. Operable patients received cisplatin and 5‐fluorouracil with concurrent radiotherapy of 60 Gy including a 2‐week break. Inoperable patients received nedaplatin and 5‐fluorouracil with concurrent radiotherapy of 60–70 Gy without a pause. End‐points were overall survival rate (OS), cause‐specific survival rate (CSS), progression‐free survival rate (PFS), and locoregional control rate (LC). Thirty‐seven operable patients and 30 medically inoperable patients were enrolled. There was a significant difference in only age between the operable group and inoperable group (P = 0.04). The median observation period was 67.9 months. In all patients, 5‐year OS, CSS, PFS, and LC were 77.9%, 91.5%, 66.9%, and 80.8%, respectively. Comparison of the operable group and inoperable group showed that there was a significant difference in OS (5‐year, 85.5% vs. 68.7%, P = 0.04), but there was no difference in CSS, PFS, or LC. Grade 3 or more late toxicity according to Common Terminology Criteria for Adverse Events v 3.0 was found in seven patients. Even in medically inoperable patients with stage I esophageal cancer, LC of more than 80% can be achieved with chemoradiotherapy. However, OS in medically inoperable patients is significantly worse than that in operable patients.     

Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis

Esophageal squamous cell cancer (ESCC) is a high‐grade carcinoma that is treated with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by surgery. Despite some success with these therapies, overall survival remains poor. In order to investigate a newer CRT regimen, we designed a comparative study to evaluate preoperative CRT using docetaxel (DOC) or 5‐Fluorouracil and cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a retrospective review of patients with resectable, locally advanced ESCC, 95 patients received preoperative CRT between 2001 and 2007. CRT was administered using either FP (n = 40) or DOC (n = 55). Pathological response and clinical outcomes were compared between the two groups. Hazard ratios and time‐to‐event analyses were used to assess outcomes; the ratios were controlled by multivariate logistic regression analysis of potential prognostic factors, and survival was presented with Kaplan–Meier curves. In the FP group, a significant curative effect was observed on the basis of pathological examination of postoperative lesions. However, the DOC group presented a significantly better prognosis on the basis of cumulative survival rates. Logistic regression analysis revealed that the presence of five or more lymph node metastases was an independent predictor of reduced survival. Patients with lymph node metastasis exhibited a better prognosis in the DOC group than those in the FP group. Preoperative CRT for locally advanced esophageal cancer using DOC results in similar or better long‐term outcomes compared with FP‐based CRT. Therefore, CRT using DOC is a promising therapy option for esophageal cancer.     

Examined lymph node count is not associated with prognosis in elderly patients with pN0 thoracic esophageal cancer

The purpose of this study was to determine whether the number of lymph nodes dissected predicts prognosis in surgically treated elderly patients with pN0 thoracic esophageal cancer. We searched the Surveillance, Epidemiology, and End Results database and identified the records of younger (<75 years) and older (≥75 years) patients with pN0 thoracic esophageal cancer between 1998 and 2015. The patient characteristics, tumor data, and postoperative variables were analyzed in this study. The Kaplan-Meier method and a Cox proportional hazard model were used to compare overall and cause-specific survival. Data from 1,792 esophageal cancer patients (older: n = 295; younger: n = 1497) were included. The survival analysis showed that the overall and cause-specific survival in the patients with ≥15 examined lymph nodes (eLNs) was significantly superior to that in the patients with 1 to 14 eLNs (P < .001); however, the difference disappeared in the older patients. After stratification by the tumor location, histology, pT classification, and differentiation between the younger and older cohorts to analyze the association between eLNs and survival, we found that the differences remained significant in most subgroups in the younger cohort. There were no differences in any subgroups of older patients. This study replicated the previously identified finding that long-term survival in patients with extensive lymphadenectomy was significantly superior to that in patients with less extensive lymphadenectomy. However, less extensive lymphadenectomy may be an acceptable treatment modality for elderly patients with pN0 thoracic esophageal cancer.     

放疗与低剂量奈达铂化疗联合治疗老年食管癌的临床研究

目的探讨放疗与低剂量奈达铂化疗联合治疗老年食管癌的临床效果。方法选取124例老年中晚期食管癌患者为研究对象,按随机数字表法将患者分为三组:单纯放疗的患者为单放组40例,放疗联合低剂量(20 mg/m2)奈达铂治疗的患者为放化1组42例,放疗联合高剂量(30 mg/m2)奈达铂治疗的患者为放化2组42例。治疗2个月后比较三组临床近期疗效,并观察三组治疗期间毒副反应发生情况。结果三组近期疗效比较差异有统计学意义(P0.05),其中放化1组疗效最佳,放化2组次之,单放组疗效最差。三组Ⅰ~Ⅱ度、Ⅲ~Ⅳ度恶心或呕吐、Ⅰ~Ⅱ度放射性肺炎、Ⅰ~Ⅱ度放射性食管炎发生率比较差异有统计学意义(P0.05),其中放化2组发生率明显高于单放组和放化1组(P0.05);放化2组Ⅲ~Ⅳ度食欲减退、Ⅲ~Ⅳ度放射性食管炎、Ⅲ~Ⅳ度骨髓抑制发生率明显高于单放组(P0.05);而放化1组仅Ⅲ~Ⅳ度食欲减退、Ⅲ~Ⅳ度骨髓抑制发生率明显高于单放组(P0.05);单放组和放化1组毒副反应以Ⅰ~Ⅱ为主,经对症治疗干预后均可明显缓解。结论与单纯放疗、放疗联合高剂量奈达铂化疗相比,放疗同步低剂量奈达铂化疗治疗老年食管癌近期疗效更显著,毒副反应轻微,更安全可靠。     

Long-term outcomes of patients with metastatic gastric cancer after initial S-1 monotherapy

Background S-1, an oral fluoropyrimidine, has been shown to have excellent activity against gastric cancer in two phase II studies and is widely used in Japan. However, the long-term outcomes of patients after S-1 monotherapy for metastatic gastric cancer are unclear. The aim of this study was to investigate the long-term outcomes in metastatic gastric cancer patients who had initially received S-1 monotherapy. Methods Ninety-two previously untreated patients with advanced gastric cancer received S-1 monotherapy as first-line chemotherapy at the National Cancer Center Hospital East, Kashiwa, Japan, and then the long-term outcomes and characteristics of long-term survivors were analyzed retrospectively. Multivariate analysis of prognostic factors was performed by the Cox proportional hazard method. Results With a median follow-up of 3.1 years, the median progression-free survival time was 4.6 months. The median survival time was 11.9 months, with 1-, 2- and 3-year survival rates of 49.1%, 22.8%, and 9.8%, respectively. Multivariate analysis showed that good performance status (P = 0.0004) and only one metastatic site (P = 0.0048) were significant independent prognostic factors. Among 48 patients with a single metastatic site, 22 with peritoneal metastasis had longer survival times (median survival, 24 months) than patients with metastasis at other sites. Among the nine 3-year survivors, six had peritoneal metastases alone. Conclusions The survival outcomes after S-1 monotherapy are promising, especially in patients with good performance status and a single metastatic site. Our findings suggest that, among patients with a single metastatic site, those with peritoneal metastases alone have a chance for long-term survival.     

A second primary esophageal cancer developing 7 years after chemoradiotherapy for advanced esophageal cancer

Received: February 3, 2000 / Accepted: August 25, 2000     

Combination therapy of S-1 and CDDP for patients with colorectal cancer

Purpose We evaluate the feasibility and efficacy of S-1 in combination with cisplatin (CDDP) for patients with colorectal cancer. Methods A total of 52 patients with advanced or recurrent colorectal cancer were included. S-1 was given orally twice daily for 21 days and CDDP 30 mg/m² on day 1 and 8, followed by a 2-week period of no treatment. Results Tumor responses among patients included 18 PR, 12 SD, and 16 PD (n = 46). The overall response rate was 36.4% (18/46). The response rate of the patients with prior chemotherapy was 22.2% (4/18) and 50.0% (12/24) among the patients who had no prior therapy. The median survival periods were 555 days and the median progression free survival periods were 183 days, respectively. S-1 in combination with CDDP shows promising activity with acceptable toxicities against colorectal cancer. Conclusions A combination of S-1 and CDDP could be a standard therapy for treating colorectal carcinoma.     

Efficacy and safety of S-1 based adjuvant chemoradiotherapy for resected pancreatic ductal adenocarcinoma with high-risk pathological feature: a prospective,single-arm,interventional study

Objective::It remains unclear whether adjuvant chemoradiotherapy (CRT) improves survival outcome of pancreatic ductal adenocarcinoma (PDAC) patients after surge...     

A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer

Background/purpose

S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer. In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer. The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80?mg/m²/day given on days 1?C21 of a 28-day cycle. This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 (UMIN000004794).

Methods

Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0?C1, adequate organ and marrow functions, and no prior anticancer therapy. Patients initially received 4?weeks of chemoradiotherapy. S-1 was given orally at a dose of 80?mg/m²/day twice daily on days 1?C21. Radiotherapy was delivered in fractions of 1.25?Gy twice daily, 5?days per week for 4?weeks (total dose: 50?Gy in 40 fractions). One month after the completion of chemoradiotherapy, S-1 was administered for 14?days followed by a 14-day rest period. This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.

Results

Fifty patients were enrolled in this phase II study. Median follow-up was 14.6?months (range 5.4?C58.9?months). Forty-three patients (86%) completed the scheduled course of chemoradiotherapy. There was no treatment-related death or grade 4 toxicity. The major toxic effects were leukopenia and nausea. The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18?C45%), stable disease in 23 (46%), and progressive disease in 12 (24%). Median progression-free survival and median overall survival were 6.7?months (95% CI, 4.7?C11.2?months) and 14.3?months (95% CI, 10.8?C20.8?months), respectively. Survival rates at 1 and 2?years were 62 and 27%, respectively.

Conclusions

Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.     

Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy

Chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rates of pathological complete response. A pathological complete response is recognized to be an important predictor of improved survival, to the extent that observation rather than surgery is advocated by some in patients with presumed pathological complete response based on their clinical response. The goal of this study was to look at the ability of clinical variables to predict pathological complete response after chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. We reviewed retrospectively patients with locally advanced esophageal squamous cell carcinoma who underwent chemoradiotherapy followed by surgery and compared those with pathological complete response to patients with residual disease. Between January 1996 and December 2010, 116 patients met inclusion criteria. Fifty‐six percent of patients had a pathological complete response and a median survival of 128.1 months versus 28.4 months in patients with residual disease. When compared with patients with residual disease, patients with a pathological complete response had a lower post‐neoadjuvant positron emission tomography (PET) maximum standardized uptake value (SUVmax), a larger decrease in PET SUVmax, a less thick tumor on post‐chemoradiotherapy computed tomography and a higher rate of normal appearing post‐chemoradiotherapy endoscopy with benign biopsy of the tumor bed. However, none of these characteristics alone was able to correctly identify patients with a pathological complete response, and none has significant specificity. Although the rate of pathological complete response after chemoradiotherapy is high in patients with esophageal squamous cell carcinoma, the ability of identifying patients with pathological complete response is limited. A reduction of the PET SUVmax by >70%, a normal appearing endoscopic examination, and no residual disease on biopsy all were seen in >65% of the patients with a pathological complete response. Even if these findings were unable to confirm the absence of residual disease in the primary tumor, they can help guide expectant management in high‐risk patients.     

Management of brain metastases in elderly patients with lung cancer

The incidence of brain metastases (BM) is continuing to grow in the elderly population with lung cancer, but these patients are seriously under-represented in clinical trials. Thus, their treatment is not based on the evidence from randomized prospective studies. Age is a well recognized poor prognostic factor for survival in patients with BM from lung cancer, which is reflected in prognostic scales, but its impact on the patients'' prognosis reflected by its value in gradually updated grading indices seems to decrease. The reason for poorer outcomes in the elderly is unknown—it may result from the influence of the age per se, simplified staging work-up and suboptimal treatment in this patient subgroup or the excess toxicity of the aggressive anticancer treatment secondary to the impaired physiological regulation mechanisms and comorbidities. The main goal of treatment of BM is to ameliorate neurological symptoms and delay neurological progression, with the focus on the improvement and maintenance of the patients’ quality of life. The possible treatment options for BM from lung cancer are whole-brain radiotherapy, stereotactic radiosurgery, surgery, chemotherapy, targeted therapies and best supportive care. The aim of this review is to summarize the problems related to the management of BM in elderly patients with lung cancer, to analyze the value of the above mentioned treatment options, and to provide an insight into the influence of age-related clinical factors on the patients’ outcomes.     

S-1-based combination therapy vs S-1 monotherapy in advanced gastric cancer:A meta-analysis

AIM:To assess the efficacy and safety of combination therapy based on S-1,a novel oral fluoropyrimidine,vs S-1 monotherapy in advanced gastric cancer(AGC).METHODS:We searched PubMed,EMBASE and the Cochrane Library for eligible studies published before March 2013.Our analysis identified four randomized controlled trials involving 790 participants with AGC.The outcome measures were overall survival(OS),progression-free survival(PFS),overall response rate(ORR)and grade 3-4 adverse events.RESULTS:Meta-analysis showed that S-1-based combination therapy significantly improved OS(HR=0.77,95%CI:0.66-0.91,P=0.002),PFS(HR=0.58,95%CI:0.46-0.72,P=0.000)and ORR(OR=2.23,95%CI:1.54-3.21,P=0.000).Sensitivity analysis further confirmed this association.Lower incidence of grade 3-4 leucopenia(OR=4.06,95%CI:2.11-7.81),neutropenia(OR=3.94,95%CI:2.1-7.81)and diarrhea(OR=2.41,95%CI:1.31-4.44)was observed in patients with S-1 monotherapy.CONCLUSION:S-1-based combination therapy is superior to S-1 monotherapy in terms of OS,PFS and ORR.S-1 monotherapy is associated with less toxicity.