scholarly journals 1413P Antibiotic administration and outcome of patients with advanced gastric cancer receiving programmed death-1 inhibitors or with single-agent chemotherapy

2021 ◽  
Vol 32 ◽  
pp. S1061
Author(s):  
M. Jung ◽  
C.G. Kim ◽  
S-J. Shin ◽  
M. Hong ◽  
H.C. Chung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Single Agent ◽  
Antibiotic Administration ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Single Agent Chemotherapy

scholarly journals OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody

2020 ◽  
Vol 122 (10) ◽  
pp. 1507-1517 ◽  
Author(s):  
Hirofumi Ohmura ◽  
Kyoko Yamaguchi ◽  
Fumiyasu Hanamura ◽  
Mamoru Ito ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Gastric Cancer Patients

Activation of central/effector memory T cells in advanced gastric cancer patients treated with antiprogrammed death-1 antibody.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 54-54 ◽  
Author(s):  
Hirofumi Ohmura ◽  
Kyoko Yamaguchi ◽  
Fumiyasu Hanamura ◽  
Mamoru Ito ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Advanced Gastric Cancer ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Effector Memory ◽  
Cytotoxic T Cell ◽  
Programmed Death ◽  
Programmed Death 1

54 Background: Anti-programmed death-1 (PD-1) monoclonal antibody, nivolumab, enhances antitumor activity by inhibiting the interaction of PD-1 and programmed death-1 ligand 1 (PD-L1) and has shown efficacy for advanced gastric cancer (AGC) in the salvage line. However, specific subsets of immune cells predominantly activated during the period of anti-PD-1 therapy for AGC have not been clarified. Methods: Peripheral blood mononuclear cells of 20 AGC patients treated with nivolumab were prospectively obtained before the initial and second administrations of nivolumab, and at the time of progressive disease (PD). The proportion of immune cell subsets were systematically analyzed by flow cytometry, including the expression of costimulatory and coinhibitory molecules such as T-cell immunoglobulin and mucin domain 3 (TIM-3), Lymphocyte-activation gene 3 (LAG-3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), cytotoxic T cell antigen-4 (CTLA-4), CD28, OX40, and inducible T cell costimulator (ICOS). Association between changes in the proportion of the subsets and therapeutic effect were analyzed. Results: Median progression free survival (PFS) of the whole patients was 51 days (95% CI 35–83). After a single course of nivolumab, patients showed a significant increase in activated effector memory and activated effector subsets of CD4+/CD8+ T cells (p = 0.018, 0.018, 0.032, 0.024). At the time of PD, proportions of myeloid dendritic cell, IgM memory B cell and Tfh-Th1/17 cell subsets decreased (p = 0.024, 0.013, 0.0039). On the other hand, LAG3 positive CD4+/CD8+ T cells, TIM-3 positive CD4+/CD8 T cells increased at the time of PD (p = 0.013, 0.032, 0.042, 0.042). Significant positive correlations were found between PFS and the proportion of LAG3 positive CD4+/CD8+ T cells (p = 0.0056, 0.0054), OX 40 positive CD4+/CD8+ T cells (p = 0.0034, 0.0006) prior to the initial nivolumab therapy. Conclusions: Nivolumab therapy enhances activation of effector memory and effector subsets of CD4+/CD8+ T cells. The expression level of LAG3 and OX40 on T cells might be correlated with efficacy of nivolumab therapy.

Programmed death 1 induces cell chemoresistance to 5-fluorouracil in gastric cancer cell lines

2016 ◽  
Vol 5 (6) ◽  
pp. 781-788 ◽  
Author(s):  
Ning Liu ◽  
Jing Lv ◽  
Weiwei Qi ◽  
Libin Sun ◽  
Jing Guo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Lines ◽  
Programmed Death ◽  
Gastric Cancer Cell Lines ◽  
Programmed Death 1

scholarly journals Effect of neoadjuvant chemotherapy on the programmed death-1 pathway in esophageal and gastric cancer

2019 ◽  
Vol 30 ◽  
pp. v301
Author(s):  
M.C. Svensson ◽  
A. Lindén ◽  
J. Nygaard ◽  
C. Hedner ◽  
B. Nodin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Programmed Death ◽  
Programmed Death 1

A phase I study of S-1 administration and a 24-h infusion of cisplatin plus paclitaxel in patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4074-4074
Author(s):  
H. Iwase ◽  
M. Shimada ◽  
T. Tsuzuki ◽  
M. Okeya ◽  
K. Kobayashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Advanced Gastric Cancer ◽  
Dose Level ◽  
Combination Chemotherapy ◽  
Single Agent ◽  
Fixed Dose ◽  
Hematological Toxicity ◽  
Level 3 ◽  
Grade 3

4074 Background: S-1 may have a major role in the treatment of gastric cancer as single agent or as a component of combination chemotherapy in Japan. We previously reported a multicentric phase II study of S-1 combined with a 24-h infusion of cisplatin in patients with advanced gastric cancer. This combination was active, safe and had the possibility of being combined with other anticancer drug. Combination chemotherapy with S-1 and cisplatin plus paclitaxel for advanced gastric cancer might yield a stronger antitumor effect. The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD), and the preliminary antitumor activity of S-1 and cisplatin plus paclitaxel for advanced gastric cancer. Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1, and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160, and 180 mg/m2). The DLT was defined as any of the following: grade 3 neutropenia lasting more than 5 days, grade 4 hematological toxicity, grade 3 non-hematological toxicity, or treatment delay of greater than 2 weeks as a result of toxicity. Results: Twenty patients were enrolled. Hematological and non- hematological toxicity of over grade 2 was not observed at dose level 1 and 2. Three patients started at dose level 3. One developed grade 3 neutropenia for 5 days following by grade 2 neutropenia lasted more than 10 days. Five more patients were added at this level. The treatment was delayed over 2 weeks in 1 out of 8 patients. Three patients started at dose level 4. One developed grade 3 neutropenia and needed longer than 14 days to recover. Three patients added this level. In total, at dose level 4 the treatment was delayed over 2 weeks in 3 out of 6 patients as a result of neutropenia. We considered level 4 is the MTD and the RD of paclitaxcel was 160 mg/m2 (dose level 3). The overall response rate was 75%. Conclusions: Triple combination chemotherapy consisting of S-1, cisplatin, and paclitaxel showed a tolerable dose of adverse reactions and favorable antitumor activity for gastric cancer. No significant financial relationships to disclose.

Second-line chemotherapy with mitomycin C and S-1 in patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14083-14083 ◽  
Author(s):  
D. Shin ◽  
S. Lee ◽  
S. Park ◽  
S. Bang ◽  
E. Cho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Mitomycin C ◽  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Previously Treated ◽  
Line Chemotherapy

14083 Background: S-1, a fourth generation oral fluoropyrimidine that mimics infusional 5-fluorouracil, has demonstrated activity against advanced gastric cancer. Based on a single agent activity and in vitro synergy between mitomycin C (MMC) and 5-fluorouracil, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for previously treated, advanced gastric cancer. Methods: Patients with measurable gastric cancer, progressive after at least one prior chemotherapy for metastatic disease, were treated with MMC 7 mg/m2 on day 1 and S-1 40 mg/m2 twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks, for up to 4 cycles. Objective response rate was the primary endpoint and was evaluated every 2 cycles of chemotherapy. With a single-stage phase II design, at least 25 patients were required. Results: Of the 26 patients registered, 24 patients were evaluable for response and 26 for safety. Eighteen patients (69%) were previously treated with 5-fluorouracil-based chemotherapy, and 10 (39%) were treated with taxanes. The patients’ median age was 55 years (range, 38–73) and 7 (27%) had an ECOG performance status of 2. A total of 64 chemotherapy cycles were delivered (median, 2; range, 1–4). In an intent-to-treat analysis, 6 patients (23%) achieved a partial response, which maintained for 3.5 months. The median progression-free and overall survivals were 4.4 months (95% CI, 1.7–7.2) and 5.4 months (95% CI, 3.4–7.4), respectively. Major toxic effects included stomatitis, diarrhea and fatigue, but were generally mild and manageable. No patient developed hemolytic reaction. Conclusions: Second-line chemotherapy with MMC and S-1 is an effective regimen for advanced gastric cancer with an acceptable toxicity profile and a convenient administration schedule. No significant financial relationships to disclose.

Irinotecan plus S-1 (IRIS) versus S-1 alone as first line treatment for advanced gastric cancer: Preliminary results of a randomized phase III study (GC0301/TOP-002)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
K. Chin ◽  
H. Iishi ◽  
H. Imamura ◽  
O. Kobayashi ◽  
H. Imamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cancer Survival ◽  
Single Agent ◽  
Rest Period ◽  
Phase Iii ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
Gastric Cancer Patients

4525 Background: Irinotecan has single agent activity and combination activity with S-1 reportedly in phase I/II studies with advanced gastric cancer patients (pts). S-1, oral fluoropyrimidine, also has activity on gastric cancer. A multicenter, randomized phase III trial comparing IRIS to S-1 alone in advanced gastric cancer was conducted. Methods: Pts with previously untreated gastric cancer were randomized to Arm A (oral S-1 80 mg/m2/day from day 1 to 28 followed by a 14-day rest period), or Arm B (oral S-1 80 mg/m2/day from day 1 to 21 and intravenous irinotecan 80 mg/m2 on days 1 and 15 followed by a 14-day rest). Treatment was continued unless disease progression was observed. Inclusion criteria: PS (ECOG) of 0 to 2; adequate major organ functions. Primary endpoint was overall survival. Results: From June 2004 to November 2005, 326 pts were randomized to arm A (162 pts) and arm B (164 pts). Pts characteristics (arm A vs. arm B) were as follows: median age: 63 vs. 63 years, PS 0–1: 97% vs. 97%, and distribution of subtype of intestinal/diffuse/others: 44%/55%/1% vs. 41%/58%/1%. Among 187 RECIST-evaluable pts (93 vs 94) reviewed by independent review panel, best response rates were 26.9% for arm A and 41.5% for arm B(p=0.035). Among 319 toxicity-evaluable patients (161 vs 158), grade 3 or 4 toxicities for arm A vs arm B (% of pts) were as follows: neutropenia 9.3% vs 26.6%, diarrhea 5.6% vs 15.8%, anorexia 9.9% vs 15.8%, nausea 3.7% vs 7.0%, vomiting 0.6% vs 2.5%. Conclusions: IRIS is effective, and well tolerated in pts with advanced gastric cancer. Survival analysis is underway. No significant financial relationships to disclose.

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