Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial

2018 ◽  
Vol 36 (19) ◽  
pp. 1922-1929 ◽  
Author(s):  
Hironori Ishigami ◽  
Yoshiyuki Fujiwara ◽  
Ryoji Fukushima ◽  
Atsushi Nashimoto ◽  
Hiroshi Yabusaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Peritoneal Metastasis ◽  
Systemic Chemotherapy ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Clinical Effects ◽  
Overall Survival Rate ◽  
Phase Iii Trial

Purpose Intraperitoneal paclitaxel plus systemic chemotherapy demonstrated promising clinical effects in patients with gastric cancer with peritoneal metastasis. We aimed to verify its superiority over standard systemic chemotherapy in overall survival. Patients and Methods This randomized phase III trial enrolled patients with gastric cancer with peritoneal metastasis who had received no or short-term (< 2 months) chemotherapy. Patients were randomly assigned at a two-to-one ratio to receive intraperitoneal and intravenous paclitaxel plus S-1 (IP; intraperitoneal paclitaxel 20 mg/m2 and intravenous paclitaxel 50 mg/m2 on days 1 and 8 plus S-1 80 mg/m2 per day on days 1 to 14 for a 3-week cycle) or S-1 plus cisplatin (SP; S-1 80 mg/m2 per day on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 for a 5-week cycle), stratified by center, previous chemotherapy, and extent of peritoneal metastasis. The primary end point was overall survival. Secondary end points were response rate, 3-year overall survival rate, and safety. Results We enrolled 183 patients and performed efficacy analyses in 164 eligible patients. Baseline characteristics were balanced between the arms, except that patients in the IP arm had significantly more ascites. The median survival times for the IP and SP arms were 17.7 and 15.2 months, respectively (hazard ratio, 0.72; 95% CI, 0.49 to 1.04; stratified log-rank P = .080). In the sensitivity analysis adjusted for baseline ascites, the hazard ratio was 0.59 (95% CI, 0.39 to 0.87; P = .008). The 3-year overall survival rate was 21.9% (95% CI, 14.9% to 29.9%) in the IP arm and 6.0% (95% CI, 1.6% to 14.9%) in the SP arm. Both regimens were well tolerated. Conclusion This trial failed to show statistical superiority of intraperitoneal paclitaxel plus systemic chemotherapy. However, the exploratory analyses suggested possible clinical benefits of intraperitoneal paclitaxel for gastric cancer.

scholarly journals Randomized Phase III Trial of Intravenous And Intraperitoneal Paclitaxel With S-1 Versus Gemcitabine Plus Nab-Paclitaxel For Pancreatic Ductal Adenocarcinoma With Peritoneal Metastasis (SP Study)

2021 ◽  
Author(s):  
Tomohisa Yamamoto ◽  
Tsutomu Fujii ◽  
Satoshi Hirano ◽  
Fuyuhiko Motoi ◽  
Goro Honda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Peritoneal Metastasis ◽  
Systemic Chemotherapy ◽  
Ductal Carcinoma ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Ductal Carcinoma ◽  
Current Standard ◽  
Phase Iii Trial ◽  
Peritoneal Washing Cytology

Abstract The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. This study has been registered with the Japan Registry of Clinical Trials, registration number jRCTs051180199 (https://jrct.niph.go.jp/).

scholarly journals Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

2013 ◽  
Vol 31 (31) ◽  
pp. 3935-3943 ◽  
Author(s):  
Atsushi Ohtsu ◽  
Jaffer A. Ajani ◽  
Yu-Xian Bai ◽  
Yung-Jue Bang ◽  
Hyun-Cheol Chung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Safety Profile ◽  
Systemic Chemotherapy ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Double Blind ◽  
Previously Treated

Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers.

The Regulatory Role of Both MBNL1 and MBNL1-AS1 in Several Common Cancers

2021 ◽  
Vol 27 ◽  
Author(s):  
Qi Zhang ◽  
Yinxin Wu ◽  
Jinlan Chen ◽  
Yuxuan Cai ◽  
Bei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Rna Splicing ◽  
Metabolic Regulation ◽  
Overall Survival Rate

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer. Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers. Methods: It was searched by the PUMUB system and summarized its expression in various cancers. Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased. Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.

Randomized phase II study to compare docetaxel plus S-1 with cisplatin plus S-1 in advanced gastric cancer without measurable lesions (HERBIS-3).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 119-119 ◽  
Author(s):  
Jin Matsuyama ◽  
Yukinori Kurokawa ◽  
Kazuhiro Nishikawa ◽  
Yutaka Kimura ◽  
Atsushi Takeno ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Oral Intake ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Phase Iii Study

119 Background: Cisplatin and S-1 (CS) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. Docetaxel is a well-known agent with high anti-tumor effect for peritoneal metastasis from gastric cancer. A previous phase III study showed docetaxel plus S-1 (DS) regimen was recommended especially for advanced gastric cancer without measurable lesions. However, there was no study comparing the efficacy and safety of these two regimens. Methods: Eligibility criteria included HER2-negative unresectable or recurrent gastric adenocarcinoma, no measurable lesion according to RECIST v1.1, no massive peritoneal metastasis, no prior chemotherapy or radiotherapy, age ≤75, PS 0-2, adequate oral intake, and preserved organ functions. Patients were randomized to receive CS (cisplatin 60 mg/m² on day 8, S-1 40–60 mg twice a day for 3 weeks, every 5 weeks) or DS (docetaxel 40 mg/m² on day 1, S-1 40–60 mg twice a day for 2 weeks, every 3 weeks). Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse events. Results: Sixty-one patients were randomly allocated the CS group (n = 31) or the DS group (n = 30) between Aug 2011 and Sep 2015. All were unresectable primary cases, and baseline characteristics were well balanced between the two groups. One patient was ineligible due to HER2-positive. There was no treatment-related death. The main grade 3 or worse adverse events were neutropenia (27% in CS vs. 40% in DS), anemia (10% in CS vs. 10% in DS), fatigue (13% in CS vs. 7% in DS), anorexia (10% in CS vs. 3% in DS), and diarrhea (10% in CS vs. 3% in DS). The median OS time were 15.8 months in CS and 20.0 months in DS, respectively (log-rank P = 0.113). Hazard ratio for OS was 0.617 (95%CI, 0.337 – 1.128). The median PFS time were 9.6 months in CS and 11.2 months in DS, respectively (log-rank P = 0.196). Hazard ratio for PFS was 0.698 (95%CI, 0.404 – 1.208). Conclusions: DS showed less toxic and more active profiles than CS for treatment of advanced gastric cancer without measurable lesions. The clinical benefit of DS regimen should be demonstrated in a phase III study. Clinical trial information: UMIN000006179.

scholarly journals The Survival Benefit and Safety of Splenectomy for Gastric Cancer With Total Gastrectomy: Updated Results†

2021 ◽  
Vol 10 ◽  
Author(s):  
Kun Yang ◽  
Zhi-Yun Zang ◽  
Kai-Fan Niu ◽  
Li-Fei Sun ◽  
Wei-Han Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Lymph Nodes ◽  
Meta Analysis ◽  
Postoperative Mortality ◽  
Sensitivity Analyses ◽  
Cochrane Central Register ◽  
Overall Survival Rate ◽  
Duration Of Surgery

BackgroundSplenectomy was traditionally performed to dissect the splenic hilar lymph nodes. Considering the important functions of spleen, whether splenectomy would bring beneficial to gastric cancer patients is debatable. This meta-analysis aimed to make an updated evaluation on the effectiveness and safety of splenectomy.MethodsLiterature searches were performed to identify eligible RCTs concerning effectiveness or safety of splenectomy with gastrectomy from PubMed, MEDLINE, CBMdisc, EMBASE, and Cochrane Central Register of Controlled Trials. Two reviewers completed the study selection, data extraction, and quality assessment independently. The meta-analyses were performed by RevMan 5.3.ResultsA total of 971 patients from four studies were included (485 in splenectomy group and 486 in spleen preservation group). Splenectomy did not increase 5-year overall survival rate (RR=1.05, 95% CI: 0.96, 1.16) or increase postoperative mortality (RR=1.21, 95% CI: 0.41, 3.54). However, the analysis demonstrated that gastrectomy with splenectomy had significantly higher incidence of postoperative complications (RR=1.80, 95% CI: 1.33, 2.45). No significant differences were found in terms of the number of resected lymph nodes and reoperation rate; however, splenectomy had a tendency to prolong the duration of surgery and hospital stays. Subgroup analyses indicated that splenectomy could not increase overall survival rate for either whole or proximal gastric cancer. Sensitivity analyses also found similar results compared to the primary analyses.ConclusionsSplenectomy cannot benefit the survival of patients with tumor located at lesser curvature, and it could instead increase postoperative morbidity.

scholarly journals Necessity of prophylactic No.10 lymph node clearance for middle and upper third gastric cancer: a network meta-analysis

2019 ◽  
Author(s):  
Gaozan Zheng ◽  
Jinqiang Liu ◽  
Yinghao Guo ◽  
Fei Wang ◽  
Shushang Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Survival Rate ◽  
Complication Rate ◽  
Perioperative Complications ◽  
Meta Analysis ◽  
Cochrane Central Register ◽  
Overall Survival Rate ◽  
The Impact

Abstract Background It remains controversial whether prophylactic No.10 lymph node clearance is necessary for gastric cancer. Thus, the present study aims to investigate the impact of prophylactic No.10 lymph node clearance on the perioperative complications and prognosis of upper and middle third gastric cancer.Methods A network meta-analysis to identify both direct and indirect evidence with respect to the comparison of gastrectomy alone (G-A), gastrectomy combination with splenectomy (G+S) and gastrectomy combination with spleen-preserving splenic hilar dissection (G+SPSHD) was conducted. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published before September 2018. Perioperative complications and overall survival were analyzed. Hazard ratios (HR) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods.Results Ten retrospective studies involving 2565 patients were included. In the direct comparison analyses, G-A showed comparable 5-year overall survival rate (HR: 1.1, 95%CI: 0.97-1.3) but lower total complication rate (OR: 0.37, 95%CI: 0.17-0.77) compared with G+S. Similarly, the 5-year overall survival rate between G+SPSHD and G+S was comparable (HR: 1.1, 95%CI: 0.92-1.4), while the total complication rate of G+SPSHD was lower than that of G+S (OR: 0.50, 95%CI: 0.28-0.88). In the indirect comparison analyses, both the 5-year overall survival rate (HR: 1.0, 95%CI: 0.78-1.3) and total complication rate (OR: 0.75, 95%CI: 0.29-1.9) were comparable between G-A and G+SPSHD.Conclusion Prophylactic No.10 lymph node clearance was not recommended for treatment of upper and middle third gastric cancer.

Proximal gastrectomy versus total gastrectomy for adenocarcinoma of the esophagogastric junction: a meta-analysis

2019 ◽  
Vol 8 (10) ◽  
pp. 753-766 ◽  
Author(s):  
Yi-chuan Chen ◽  
Li Lu ◽  
Kai-hu Fan ◽  
Dao-han Wang ◽  
Wei-hua Fu
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Total Gastrectomy ◽  
Recurrence Rate ◽  
Meta Analysis ◽  
Proximal Gastrectomy ◽  
Cochrane Library ◽  
Overall Survival Rate ◽  
Upper Third

Aim: To compare efficacy between total gastrectomy (TG) and proximal gastrectomy (PG) for upper-third gastric cancer. Materials & methods: PubMed, Embase and Cochrane library were searched to select suitable researches. Stata was used for meta-analysis including 5-year overall survival rate, recurrence rate, complication morbidities and serum nutritional levels. Results: Ten retrospective English researches were contained. Our study showed no significant difference of 5-year overall survival rate, recurrence rate, reflux symptoms and anastomotic leakage. TG experienced longer operation time, more lymph nodes-retrieved number, more estimated blood loss and higher ileus, but less anastomotic stricture. PG showed advantages over TG in terms of serum nutritional levels. Conclusion: PG is more preferable to TG for treatment of upper-third gastric cancer.

scholarly journals Pharmacotherapy for liposarcoma: current and emerging synthetic treatments

2021 ◽  
Author(s):  
Florence Chamberlain ◽  
Charlotte Benson ◽  
Khin Thway ◽  
Paul Huang ◽  
Robin L Jones ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Subgroup Analysis ◽  
Systemic Chemotherapy ◽  
Median Overall Survival ◽  
Soft Tissue Sarcomas ◽  
Phase Iii ◽  
Targeted Agents ◽  
Phase Iii Trial ◽  
Localized Disease

Liposarcomas are rare tumors arising from adipocytic tissue and accounting for approximately 15–20% of all soft tissue sarcomas. Liposarcoma can be further classified into histopathological subtypes with variable chemosensitivity according to subtype. Decisions regarding management should be made on an individual basis, but surgery for localized disease and systemic chemotherapy remain the mainstay of treatment. Currently, only doxorubicin and trabectedin have robust Phase III data to support their use in the management of advanced liposarcoma. However, in the subgroup analysis of a Phase III trial comparing eribulin with dacarbazine, there was a greater than 7-month improvement in median overall survival in those treated with eribulin. There are also promising results from emerging studies in novel and targeted agents for the treatment of liposarcoma.

scholarly journals Necessity of prophylactic splenic hilum lymph node clearance for middle and upper third gastric cancer: a network meta-analysis

2020 ◽  
Author(s):  
Gaozan Zheng ◽  
Jinqiang Liu ◽  
Yinghao Guo ◽  
Fei Wang ◽  
Shushang Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Survival Rate ◽  
Complication Rate ◽  
Perioperative Complications ◽  
Meta Analysis ◽  
Cochrane Central Register ◽  
Overall Survival Rate ◽  
The Impact

Abstract Background It remains controversial whether prophylactic No.10 lymph node clearance is necessary for gastric cancer. Thus, the present study aims to investigate the impact of prophylactic No.10 lymph node clearance on the perioperative complications and prognosis of upper and middle third gastric cancer. Methods A network meta-analysis to identify both direct and indirect evidence with respect to the comparison of gastrectomy alone (G-A), gastrectomy combination with splenectomy (G+S) and gastrectomy combination with spleen-preserving splenic hilar dissection (G+SPSHD) was conducted. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published before September 2018. Perioperative complications and overall survival were analyzed. Hazard ratios (HR) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. Results Ten retrospective studies involving 2565 patients were included. In the direct comparison analyses, G-A showed comparable 5-year overall survival rate (HR: 1.1, 95%CI: 0.97-1.3) but lower total complication rate (OR: 0.37, 95%CI: 0.17-0.77) compared with G+S. Similarly, the 5-year overall survival rate between G+SPSHD and G+S was comparable (HR: 1.1, 95%CI: 0.92-1.4), while the total complication rate of G+SPSHD was lower than that of G+S (OR: 0.50, 95%CI: 0.28-0.88). In the indirect comparison analyses, both the 5-year overall survival rate (HR: 1.0, 95%CI: 0.78-1.3) and total complication rate (OR: 0.75, 95%CI: 0.29-1.9) were comparable between G-A and G+SPSHD. Conclusion Prophylactic No.10 lymph node clearance was not recommended for treatment of upper and middle third gastric cancer.

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