scholarly journals Concurrent chemoradiotherapy with S-1 compared with concurrent chemoradiotherapy with docetaxel and cisplatin for locally advanced esophageal squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  

Abstract Background This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. Results A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). Conclusion CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

2020 ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  

Abstract Background: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients who had locally advanced ESCC and received CCRT with S-1 (70mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25mg/m2) and cisplatin (25mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Treatment-related toxicities, response rate, and survival outcomes were compared between groups. Results: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than in the DP group (22.2% versus 45.6%, p = 0.002). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% versus 25.0%, p = 0.275). Conclusion: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4073-4073
Author(s):  
Jinming Yu ◽  
Xue Meng ◽  
Jian hua Wang ◽  
Xindong Sun ◽  
Lv hua Wang ◽  
...  

4073 Background: In China more than 90% of esophageal malignancies are of squamous cell carcinoma (SCC). We conducted this Chinese multicenter trial to determine the efficacy and safety of the addition of cetuximab with paclitaxel, cisplatin, and concurrent radiation for patients with esophageal SCC and to determine whether KRAS status predicts response. Methods: Patients with unresectable locally advanced cervical, upper or mid-esophageal SCC without distant metastasis were eligible for this open-label phase II trial. All patients received cetuximab (400 mg/m2 day 1 before chemoradiotherapy and 250 mg/m2 q1w × 7 weeks), paclitaxel (45 mg/m2 q1w × 7 weeks) and cisplatin (20 mg/m2 q1w × 7 weeks) with 59.4 Gy of radiation. The primary end point was response rate. Second end points included toxicity, overall survival (OS), progression-free survival (PFS), and KRAS mutation status. Results: Fifty-five patients were enrolled and evaluable to safety. Non-hematological adverse events were generally grade 1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue (45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia (1.82%). Ten patients did not complete the protocol therapy (6 for chemotherapy dose delays, 1 for paciltaxel hypersensitivity, 1 by the treating physicians for unstated reasons, 1 for concurrent unrelated infection, and 1 for tracheo-esophageal fistula). The response rate was 97.7%. The 1-year OS and median OS was 87.3% and 16.8 months, the 1-year PFS and median PFS was 30.4% and 13.9 months, respectively. No mutations were detected at KRAS codons 12 or 13 in the 52 available specimens. Conclusions: Cetuximab can be safely administered with chemoradiation for Chinese patients with esophageal cancer and may improve the clinical response rate. KRAS mutations were too rare to be analyzed as a predictor of response.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4074-4074
Author(s):  
Hironaga Satake ◽  
Makoto Tahara ◽  
Satoshi Mochizuki ◽  
Sadamoto Zenda ◽  
Takashi Kojima ◽  
...  

4074 Background: Standard of care for unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is concurrent chemoradiotherapy (CRT). However, its survival remains limited. Neoadjuvant chemotherapy with docetaxel, cisplatin and 5-FU (DCF) demonstrated promising activity with pathological complete response (CR) of 22% for resectable stage II/III ESCC (Hara H et.al, ASCO 2012). This study was performed to assess the efficacy and safety of induction chemotherapy with DCF followed by CRT in patients with unresectable locally advanced ESCC. Methods: Eligibility criteria included clinically T4 and/or M1 lymph node (LYM) ESCC, PS 0-1, and 20-70 years old. Treatment consisted of docetaxel 70 mg/m2, cisplatin 70 mg/m2 on day 1 and fluorouracil 750 mg/m2 on days 1 to 5, repeated every 3 weeks for three cycles, followed by cisplatin 70 mg/m2 on days 64 and 92, and fluorouracil 700 mg/m2on days 64 to 67 and 92 to 95 concurrently with radiotherapy (60Gy in 30 fractions, 5 days/week). Results: From August 2009 to November 2011, 33 patients were enrolled.There were 16 pts with T4M0 disease, 13 with nonT4M1 LYM, and 4 with T4M1 LYM.Most grade 3 or 4 toxicities were neutropenia (66%), leukopenia (39%), anorexia (18%), dysphasia (12%), nausea (9%), febrile neutropenia (6%), and hyponatremia (6%) during induction chemotherapy. Most grade 3 or 4 toxicities were leukopenia (27%), neutropenia (20%), dysphasia (17%), anorexia (13%), esophagitis (13%), nausea (10%), and febrile neutropenia (3%) during CRT. No treatment related death was observed. The completion rate of protocol treatment was 88% (29/33). The overall response rate after completion of induction chemotherapy was 61%. Eleven pts (38%) achieved CR after completion of protocol treatment. With a median follow-up period of 14 months, 1y-PFS and 1y-OS are 38.5 and 78.6 %, respectively. Of a total of 33 patients, eighteen patients (55%) received secondary treatment. Conclusions: Induction chemotherapy with DCF followed by CRT in unresectable locally advanced ESCC was well tolerated. Although these data are preliminay, this approach warrants further evaluation. Clinical trial information: UMIN000003370.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Delin Liu ◽  
Qin Zhang ◽  
Jinghua Zhu ◽  
Ting Qian ◽  
Rong Yin ◽  
...  

e16029 Background: Compared with neoadjuvant chemotherapy alone,Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15520-15520 ◽  
Author(s):  
A. A. Javed ◽  
A. Shaharyar ◽  
I. H. Shah ◽  
M. A. Shah ◽  
T. N. Ansari ◽  
...  

15520 Background: The optimum radiosensitizing dose and schedule of gemcitabine for squamous cell carcinoma of head and neck are not known. The objectives of this study were to evaluate the efficacy and toxicity of weekly gemcitabine as a radiosensitizer concurrent with radical radiotherapy in locally advanced head and neck cancer. Method: Thirty-nine patients with stage III or IV B inoperable carcinoma of head and neck were enrolled. Eligible patients had histopathologically confirmed squamous cell carcinoma with age between 18–70 years. Patients had a KPS >70 with an adequate marrow, hepatic and renal function. No prior chemotherapy or radiotherapy was allowed. Patients with nasopharyngeal, glottic or sub-glottic cancer were excluded. Gemcitabine 150 mg/m2 or a total dose not exceeding 200 mg was given on day 1,8,15,22,29, and 36 during radiation treatment. Gemcitabine was infused in 200 ml of normal saline in 2 hours and radiation was delivered two hours after the completion of gemcitabine infusion. Conventional fractionation was used to deliver a total dose of 66 Gy. CTC version 2.0 of NCI and RTOG/EORTC Late Radiation Morbidity Scoring Scheme were used for evaluation of toxicity and RECIST was used for response evaluation. Results: Only 35 patients were considered evaluable for response. Complete response was seen in 8 (22.9%) (95% CI; 10.4–40.1%), partial response in 25 (71.4%), with an overall response rate of 94.3% (95% CI; 80.8–99.3%). All the thirty-nine patients were evaluable for toxicity. Grade 3 and 4 mucositis was seen in 28 (71.8%) and 2 (5.1%) patients respectively. Grade 3 pharyngeal toxicity was seen in 6 (15.4%). One patient developed pharyngo-cutaneous fistula. Despite vigorous symptomatic and supportive care acute toxicities led to treatment interruption in 16 (41%) of patients. Conclusion: Weekly gemcitabine at a dose of 150mg/m2 concurrent with radiation therapy gives a high overall response rate and a high rate of acute toxicity. No significant financial relationships to disclose.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 79-79
Author(s):  
C. Lin ◽  
C. Hsu ◽  
J. C. Cheng ◽  
C. Yen ◽  
H. Shiah ◽  
...  

79 Background: We investigated the efficacy and safety of adding cetuximab into twice-weekly paclitaxel/cisplatin-based concurrent chemoradiotherapy (CCRT), followed by surgery, for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with operable ESCC (T3N0-1M0 or T1-3N1M0 or M1a) were treated with paclitaxel (35 mg/m2 1 h on days 1 and 4/week), cisplatin (15 mg/m2 1 h on days 2 and 5/week), cetuximab (400 mg/m2 2 h on day -5, then 250 mg/m2 2 h on day 3/week) and radiotherapy (2 Gy on days 1-5/week). When the accumulated radiation dose reached 40 Gy, the feasibility of esophagectomy was evaluated for all patients. In patients for whom esophagectomy was not feasible, CCRT was continued to a radiation dose of 60-66 Gy. Results: Sixty-two patients with ESCC were enrolled, and the majority had T3N1M0 or M1a tumors by endoscopic ultrasonographic staging (94%). All patients received CCRT to 40 Gy. Forty-three patients underwent surgery, and 17 patients continued definitive CCRT to 60-66 Gy. Of the scheduled doses of paclitaxel, cisplatin, and cetuximab, 80%, 79%, and 99% were given, respectively. The intent-to-treat pathological complete response rate was 24% (15/62) (95% confidence interval: 13-35%). At the median follow-up of 13.3 months, the one-year progression-free and overall survivals were 76% and 63%, respectively. The most common grade 3/4 toxic effects were leukopenia (51%), neutropenia (15%), esophagitis (19%), and infection (12%). Grade 1, 2, and 3 skin rash occurred in 59%, 36%, and 2% of patients, respectively. Grade 1, 2, 3, and 4 hypomagnesemia occurred in 14%, 5%, 0%, and 5% of patients, respectively. Conclusions: Adding cetuximab to twice-weekly paclitaxel/cisplatin-based CCRT prior to esophagectomy is an active and tolerable treatment for locally advanced ESCC. No significant financial relationships to disclose.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 101-101
Author(s):  
Xiaoyuan Wu ◽  
Yongshun Chen ◽  
Yuanyuan Yang ◽  
Daxuan Hao ◽  
Xue Li ◽  
...  

101 Background: Preoperative chemoradiotherapy is an accepted standard treatment for patients with locally advanced esophageal cancer. Nimotuzumab is a monoclonal antihuman EGFR IgG1 antibody that has demonstrated synergistic activity with both radiotherapy and platinum-based chemotherapy in some solid tumors. The aim of this study is to investigate the safety and efficacy of nimotuzumab in combination with preoperative concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Previously untreated patients with stage II-III ESCC received nimotuzumab (200mg per week in weeks1-5), paclitaxel(45 mg/m2 per week in weeks 2-5), cisplatin(20 mg/m2 per week in weeks 2-5) and radiotherapy at a total dose of 40 Gy (2.0Gy/d,5 days per week in weeks 2-5). Esophagectomy was performed 4 weeks after the completion of preoperative strategies. Results: Eighteen eligible patients were enrolled. All patients completed the preoperative regimen, and seventeen patients underwent surgery. The clinical response rate was 94.4% (17/18). The most frequent Grade 1/2 toxicities were esophagitis(12/17), leukocytopenia(14/17), nausea/vomiting(8/17) and fatigue(4/17). Grade 3 leukocytopenia was observed in 11.8 % of patients (3/17). The rate of radical resection was 100%, and the pathological complete response rate was 41.2%(7/17). Downstaging occurred in 15/17 (88.2 %) patients by T stage and 8/17 (47.1%) by N stage. The incidences of postoperative anastomotic leak, pulmonary infection, hoarseness and arrhythmia were 11.8%, 11.8%, 5.9%, and 5.9%, respectively. No perioperative deaths occurred in the study. Conclusions: The regimen of nimotuzumab in combination with preoperative concurrent chemoradiotherapy is safe for locally advanced ESCC. The preoperative strategy is able to achieve substantially high clinical response rate and pathological complete response rate.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4055-4055
Author(s):  
Dashan Ai ◽  
Yun Chen ◽  
Qi Liu ◽  
Xiangpeng Zheng ◽  
Yunhai Li ◽  
...  

4055 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC) . Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. TP group had a significant higher incidence of acute grade 3/4 neutropenia (59.7% vs. 16.8%(TF) or 32.4%(TC)), thrombocytopenia (12.7% vs. 3.5%(TF) or 6.2%(TC)), anemia (6.4% vs. 4.4%(TF) or 4.4%(TC)), fatigue (10.0% vs. 0.9%(TF) or 0.9%(TC)) and vomiting (5.5% vs. 0%(TF) or 0.9%(TC)) than other two groups ( P < 0.05). TF group had a significant higher incidence of grade 3/4/5 esophagitis (13.1% vs. 1.8%(TP) or 5.3%(TC)) and pneumonitis (4.4% vs. 0%(TP) or 1.8%(TC)) than other two groups ( P < 0.05). One patient in TF group died of acute pneumonitis. One patient in TF group and one in TC group died of acute esophagitis. Conclusions: TP and TF regimen showed different severe AEs in CCR in ESCC patients and TC showed mild AEs. Clinical trial information: NCT02459457.


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