Preoperative chemotherapy with cisplatin in combination with docetaxel and gemcitabine in locally advanced non-small-cell lung cancer

Despite surgery, both locoregional and distant disease controls remain poor in stage III non-small-cell lung cancer (NSCLC). Preoperative chemotherapy has become an accepted treatment but no established regimen exists. Our objective was to define the activity and feasibility of cisplatin in combination with docetaxel and gemcitabine in stage III NSCLC followed by surgery or radiotherapy. Thirty-two chemotherapy-naive patients with NSCLC (59% stage IIIAN2, 41% stage IIIB) received cisplatin 75 mg/m² on day 1, gemcitabine 1,000 mg/m² on days 1 and 8, and docetaxel 20 mg/m² on days 1, 8 and 15. Patients received induction chemotherapy (3 cycles) before re-evaluation, followed by thoracotomy or thoracic radiotherapy. Radiographic response was 50% and stable disease at computed tomography (CT) scan was observed in 30% of patients. Thirty patients were evaluable for response; thoracotomy was performed in 16 patients (53%) and resection was complete in 8 patients (27%). Grade 3/4 neutropenia, the main hematologic toxicity, occurred in 53% of patients but only 3 patients required hospitalization due to neutropenic fever. Severe non-hematologic toxicity was uncommon. There were 3 treatment-related deaths. To date, 22% of patients remain alive and disease-free with a median follow-up of 13 months. Median survival for all recruited patients was 14 months, with an estimated 1-year survival rate of 60%. The combination of cisplatin/docetaxel/gemcitabine is a welltolerated regimen. Although it has potential serious toxic effects, high response rates and manageable toxicity justify its use in further trials. The Spanish Lung Cancer Group (SLCG) is currently performing a trial with this regimen in stage III disease.     

Validity of neoadjuvant chemotherapy with docetaxel,cisplatin, and S-1 for resectable locally advanced gastric cancer

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.     

Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer

A phase I study of S-1 and biweekly docetaxel (DOC) combination therapy was conducted to determine the maximum tolerated dose (MTD) and pharmacokinetic parameters. Fourteen patients with advanced or recurrent gastric cancer were analyzed. The treatment consisted of S-1 [body surface area (BSA) <1.25 m2:80 mg/day, 1.25相似文献   

Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination

Purpose

Peritoneal dissemination is the most frequent and life-threatening mode of metastasis and recurrence in patients with gastric cancer. A multicenter phase II study was designed to evaluate the efficacy and tolerability of S-1 and docetaxel combination chemotherapy regimen for the treatment of advanced or recurrent gastric cancer patients with peritoneal dissemination.

Methods

Nineteen patients with histologically confirmed unresectable or recurrent gastric cancer with peritoneal dissemination were enrolled. Oral S-1 at 80 mg/m²/day was administered twice daily for 2 weeks, followed by 1 drug-free week. Docetaxel infusion at 40 mg/m² was performed on day 1, simultaneous with S-1 administration. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary endpoints were the response rates and safety status.

Results

Patients received a median of 4 cycles of the S-1 and docetaxel regimen (range 1–43). The disease control rate was 73.7 % (14/19). Median overall survival was 459 days (15.3 months), while median time to progression was 212 days (7.1 months). Neutropenia was the most common type of toxicity (n = 7, 36.8 %).

Conclusions

Combination chemotherapy with S-1 and docetaxel is a tolerable and effective treatment for advanced or recurrent gastric cancer patients with peritoneal dissemination.     

Analysis of four patients with advanced gastric cancer undergoing gastrectomy after pre-operative combination chemotherapy using docetaxel, cisplatin and S-1

We analyzed the clinical efficacy of pre-operative combination chemotherapy using docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were enrolled and staging laparoscopy was performed. Patients received intravenous docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day 1-14 every 4 weeks. Two patients received two courses of chemotherapy and two patients received three courses of chemotherapy. Neutropenia of more than grade 3 was found in 3 cases. All cases were PR on preoperative imaging. Curative operation was performed on three cases. Histological anti-tumor effect was judged to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all patients received S-1-based adjuvant chemotherapy. The combination chemotherapy using docetaxel, cisplatin and S-1 plus operation was a candidate for the standard treatment strategy for advanced gastric cancer.     

含替吉奥联合化疗方案治疗进展期胃癌研究的进展

替吉奥胶囊（Ｓ-１）是替加氟及优福定的升级换代产品,使用替吉奥联合化疗方案治疗晚期胃癌在不同的临床研究中取得了初步肯定的治疗效果,毒副作用小,疗效确切,给药方便。本文就含替吉奥联合化疗方案治疗进展期胃癌的研究进展作一综述。     

Preoperative combination chemotherapy with S-1 and low dose cisplatin against highly advanced gastric carcinoma

We performed preoperative chemotherapy with S-1 and low-dose CDDP (TSLD) to treat 9 patients of highly advanced gastric cancer. Five cases showed significant effect with severe fibrosis diagnosed as grade 1b-2 effect in histology, and all 9 cases showed at least grade 1a effect in either primary lesion or lymph node. While toxicity of less than grade 3 (gastrointestinal disorder and/or bone marrow suppression) were observed in 5 out of 9 cases (55.6%), no symptom was observed in 3 out of the 5 patients. We conclude that the TSLD is useful to control highly advanced gastric cancer.     

Combination chemotherapy of S-1 and docetaxel on advanced and recurrent gastric cancer

In the present article, we have summarized the phase I/II clinical trials on combination therapy of S-1 and docetaxel. With result of the phase I study, patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1 and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients received a total of 272 treatment cycles. No complete responses (CRs) and 27 partial responses (PRs) were observed for an overall response rate (CR+PR) of 56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3 patients (6.2%) had progressive disease (PD) as best response. The tumor control rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3 months (95% CI: 10.7-20.3 months) and the median time to tumor progression was 7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%, and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia 14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all treatment-related toxicities were resolved. The mechanisms underlying these synergistic effects of S-1 and docetaxel were examined by expression and activity analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric cancer cell. These findings strongly indicate that the combination chemotherapy of docetaxel and S-1 is effective against gastric carcinomas and therefore is a good candidate as a standard chemotherapeutic strategy in treating these tumors.     

周剂量紫杉醇联合替吉奥治疗晚期胃癌(英文)

Objective:There remains no standard first-line chemotherapeutic regimen for advanced gastric cancer (AGC).The aim of this study was to evaluate the efficacy and safety of combination regimen with weekly paclitaxel and S-1 as a first-line chemotherapy for AGC. Methods:Forty-six patients with AGC were included in this study. Paclitaxel was administered weekly at a dose of 60 mg/m2 on days 1, 8 and 15, S-1 was administered orally twice daily at 80 mg/m2/day for 2 weeks. The regimen was repeated every four weeks. Results:The results showed that the overall response rate was 45.7%, with 3 patients achieved complete response and 18 patients had a partial response, the disease control rate was 76.1%. The median progress free survival was 7.2 months 95% confidence interval (CI):6.3-8.1 months and the median overall survival was 11.6 months (95% CI:10.6-12.6 months) after treatment with paclitaxel and S-1. Neutropenia occurred in 25 patients (54.3%) and grade 3/4 neutropenia was observed in 8 patients (17.4%), gastrointestinal reactions were the most common non-hematologic toxicities, while severe gastrointestinal toxicities were uncommon. Conclusion:The regimen of weekly paclitaxel and S-1 demonstrated activity and acceptable toxicity for AGC as a first-line chemotherapy.     

A case of locally advanced gastric cancer responding to preoperative S-1/CDDP combination chemotherapy

A 59-year-old man visited our department with the complaint of an abdominal mass. After detailed examination, he was diagnosed with cT3 (SE) N2M0, cStage III C gastric cancer and underwent a 3 course preoperative S-1/CDDP combination chemotherapy. After tumor down-staging was achieved after the 3 course combination chemotherapy, a surgery was scheduled. The patient underwent distal gastrectomy with D2 lymph node dissection. Histopathological diagnosis was M, type 1, 75 × 35 mm, papillary>moderately-differentiated tubular adenocarcinoma [pT2 (MP), ly3, v0, pN2, Stage IIB]. The patient is now treated with oral S-1 as postoperative adjuvant chemotherapy on an outpatient basis, and there are no signs of recurrence as of 1 year after the surgery. Preoperative chemotherapy appears to be a promising treatment option for gastric cancer with extensive lymph node metastasis.     

Phase II trial of preoperative chemotherapy with docetaxel, cisplatin and S-1 for T4 locally advanced gastric cancer

The standard treatment for T4 locally advanced gastric cancer is gastrectomy with D2 lymph node dissection followed by adjuvant chemotherapy with S-1 for 12 months; however, prognostic outcome in Stage IIIb has been insufficient. It is expected that survival is improved by preoperative treatment with a triplet regimen of docetaxel, cisplatin and S-1 (divided DCS therapy). A multicenter Phase II study has been conducted to evaluate the safety and efficacy of two courses of preoperative chemotherapy followed by gastrectomy. Fifty-five patients are required for this study. The primary endpoint of the study is pathological response rate of primary lesions. Secondary endpoints are overall survival, disease-free survival, R0 resection rate and adverse events.     

Phase II study of biweekly docetaxel and S-1 combination chemotherapy as first-line treatment for advanced gastric cancer

Purpose

We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer.

Methods

Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0?C2 and no prior chemotherapy history were eligible for inclusion (n?=?45). Patients received a total of 215 treatment courses (median, 4; range, 2?C12) of S-1 oral administration twice daily for 1?week followed by a drug-free interval of 1?week. Docetaxel (40?mg/m²) was administered intravenously on days 1 and 15.

Results

We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3?months, the median time to progression was 6.9?months, and the median duration of response in 26 patients was 8.0?months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths.

Conclusions

S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.     

A case report of advanced gastric cancer with peritoneal dissemination effectively treated by combination chemotherapy of S-1 and docetaxel

The present patient was a 69-year-old male diagnosed as gastric cancer with peritoneal dissemination by staging laparoscopy. He was treated with chemotherapy using S-1 (120 mg/body/day) and docetaxel (70 mg/body/day 1) administered for 2 weeks, followed by one drug-free week in three-week courses. After 4 courses of treatment, the primary tumor regressed, but only slightly. Because of an adverse event, we continued with a lower dose. After 4 more courses of treatment, the primary tumor and dissemination were undetectable on abdominal CT scan but were endoscopically detected. The patient has been followed on an outpatient basis without surgical treatment for 2 years.     

A case of advanced gastric cancer showing pathological CR after neoadjuvant chemotherapy with docetaxel, cisplatin and S-1 combination

A 69-year-old man suffering from heart-burn was referred to our hospital, and diagnosed as type 3 advanced gastric cancer with lymph node metastasis. Neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin and S-1 was attempted. After two courses of chemotherapy were completed, distal gastrectomy with D2 lymphadenectomy was performed. Pathologically, there were no viable cancer cells remaining in the primary lesion and lymph nodes. The pathological response of NAC was judged to be grade 3. The postoperative course was uneventful, and the patient is currently visiting our outpatient clinic for treatment with S-1 as postoperative adjuvant chemotherapy.     

Phase I study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer

The aim of this dose escalation study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and preliminary efficacy of docetaxel, S-1 and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Seventeen patients received oral S-1 (40 mg m(-2) bid) on days 1-14, intravenous cisplatin (60 mg m(-2)) and docetaxel (60, 70 or 80 mg m(-2) depending on DLT) on day 8 every 3 weeks. The MTD of this combination was presumed to be docetaxel 70 mg m(-2). At this dose level, 40% of the patients (two of five) developed grade 4 neutropenia and 20% (one of five) exhibited grade 3 nausea during the first course. Therefore, the recommended dose of docetaxel was defined as 60 mg m(-2). The DLT was neutropenia. The response rate (RR) was 88.2% (15 of 17), consisting of one complete response and 14 partial responses. There were two stable diseases but no progressive disease. Of these 15 responders, four (23.5%) with high VEGF expression showed rapid tumour regression and achieved downstaging, leading to subsequent curative gastrectomy. Three of these have been disease free for about 3 years, suggesting a complete cure. In conclusion, this regimen was tolerable and showed a quite high RR, with an appreciable downstaging rate in metastatic gastric cancer.     

Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer

Purpose

We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer.

Methods

Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0–2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m² b.i.d.) on days 1–14 and intravenous cisplatin (60 mg/m²) and docetaxel (60 mg/m²) on day 8 every 3 weeks.

Results

Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44–77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0–1,138.1] and 226 days (95% CI, 182.5–379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed.

Conclusions

DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.     

Combination chemotherapy of S-1 plus biweekly docetaxel for advanced and recurrent gastric cancer

The S-1 +biweekly docetaxel (DOC) combination therapy was evaluated for advanced or recurrent gastric cancer patients. This combination therapy was evaluated in vitro using the nude rat-gastric cancer xenograft system. S-1 alone or DOC alone showed antitumor activity, and the antitumor activity was synergistic when two drugs were combined. In clinical settings, the schedule was S-1 80 mg/m2 (day 1-14, orally) and DOC (day 1 and day 15, intravenously) followed by a 2-week rest. In phase I study, the dose of DOC was evaluated, and a recommended dose for phase II was determined as 35 mg/m2. The entry for phase II study was completed, and the preliminary results of 33 patients showed the response rate of 21.2%. The incidence of more than grade 3 adverse effects was 29%(neutropenia, leukocytopenia, anorexia and mucositis). The S-1 +biweekly DOC combination therapy can be a candidate for outpatient chemotherapy for advanced or recurrent gastric cancer.