Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

Takashima, Atsuo; Shitara, Kohei; Fujitani, Kazumasa; Koeda, Keisuke; Hara, Hiroki; Nakayama, Norisuke; Hironaka, Shuichi; Nishikawa, Kazuhiro; Kimura, Yutaka; Amagai, Kenji; Fujii, Hirofumi; Muro, Kei; Esaki, Taito; Choda, Yasuhiro; Takano, Toshimi; Chìn, Keisho; Satō, Atsushi; Goto, Masahiro; Fukushima, Noriyoshi; Hara, Takuya; Machida, Nozomu; Ohta, Michio; Boku, Narikazu; Shimura, Masashi; Morita, Satoshi; Koizumi, Wasaburo

doi:10.1007/s10120-018-0838-6

Cited by 45 publications

(40 citation statements)

References 17 publications

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“…This theory is consistent with taxan-containing therapies showing superior results than other regimens for treating gastric cancer [37,38]. Half of the patients with unresectable GC have PM at the time of second-line chemotherapy induction [2,38]. Because ICI was used after treatment failure of taxan-containing therapies, the phenotype of macrophages may have changed from M1 to M2 in the PM TME.…”

Section: Discussionsupporting

confidence: 55%

“…Low-dose paclitaxel changed macrophage phenotype from M2 to M1 through the toll-like receptor (TLR)-4, resulting in tumor growth inhibition [35,36]. This theory is consistent with taxan-containing therapies showing superior results than other regimens for treating gastric cancer [37,38]. Half of the patients with unresectable GC have PM at the time of second-line chemotherapy induction [2,38].…”

Section: Discussionmentioning

confidence: 64%

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Established fibrous peritoneal metastasis in an immunocompetent mouse model similar to clinical immune microenvironment of gastric cancer

Fujimori

Kinoshita

Yamaguchi

et al. 2020

Preprint

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Background Peritoneal metastasis (PM) in gastric cancer (GC) is characterized by diffusely infiltrating and proliferating cancer cells accompanied by extensive stromal fibrosis in the peritoneal space. The prognosis of GC with PM is still poor regardless of the various current treatments. In order to elucidate the cause of difficulties in PM treatment, we compared the tumor immune microenvironment (TME) in primary and PM lesions in GC. In addition, a PM model with fibrous stroma was constructed using immunocompetent mice to determine whether its TME was similar to that in patients. Methods Immuno-histochemical analyses of infiltrating immune cells were performed in paired primary and PM lesions from 28 patients with GC. A C57BL/6J mouse model with PM was established using the mouse GC cell line YTN16 either with or without co-inoculation of mouse myofibroblast cell line LmcMF with a-SMA expression. The resected PM from each mouse model was analyzed the immunocompetent cells using immunohistochemistry.Results The number of CD8+ cells was significantly lower in PM lesions than in primary lesions (P<0.01). Conversely, the number of CD163+ cells (M2 macrophages) was significantly higher in PM lesions than in primary lesions (P=0.016). Azan staining revealed that YTN16 and LmcMF co-inoculated tumors were more fibrous than tumor with YTN16 alone (P<0.05). Co-inoculated fibrous tumor also showed an invasive growth pattern and higher progression than tumor with YTN16 alone (P=0.045). Additionally, YTN16 and LmcMF co-inoculated tumors showed lower infiltration of CD8+ cells and higher infiltration of M2 macrophages than tumors with YTN16 alone (P<0.05, P<0.05). These results indicate that LmcMF plays as cancer-associated fibroblasts (CAFs) by crosstalk with YTN16 and CAFs contribute tumor progression, invasion, fibrosis, and immune suppression.Conclusions This model is the first immunocompetent mouse model to accurately reflect the similar to TME of human clinical PM with fibrosis. By using this model, new treatment strategies for PM, such as anti-CAFs therapies, may be developed.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 64%

Established fibrous peritoneal metastasis in an immunocompetent mouse model similar to clinical immune microenvironment of gastric cancer

Fujimori

Kinoshita

Yamaguchi

et al. 2020

Preprint

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“…In a subgroup analysis, PFS in patients with moderate/massive ascites tended to be better with nab-PTX plus RAM than PTX plus RAM. The ABSOLUTE trial, which demonstrated the non-inferiority of weekly nab-PTX to weekly PTX for patients with AGC, also suggested an increased efficacy of weekly nab-PTX in patients with ascites or peritoneal metastasis [11,16]. While the reason for this remains unclear, a multicenter randomized phase II P-SELECT trial of nab-PTX plus RAM versus PTX plus RAM as second-line therapy for AGC patients with peritoneal dissemination (WJOG10617G, jRCTs031180022) is underway and may confirm this observation.…”

Section: Discussionmentioning

confidence: 99%

Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

Okunaka

Kotani²,

Demachi

et al. 2020

Preprint

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Background Nanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC. Methods This study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital. Results A total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]: 3.4–4.3) in the nab-PTX plus RAM group and 3.9 months (95% CI: 3.1–4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83–1.40; P = 0.573). Median overall survival (OS) was 10.9 months (95% CI: 9.3–12.7) in the nab-PTX plus RAM group and 10.3 months (95% CI: 8.5–12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61–1.10; P = 0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group. Conclusions The combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC.

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“…As mentioned previously, GCYA patients are likely to have good bone marrow function and could tolerate this intensive regimen. Furthermore, in a subgroup analysis of the ABSOLUTE trial, 32 it has been reported that nab-paclitaxel has greater efficacy for peritoneal metastasis than paclitaxel. Most GCYA patients had diffuse-type histology.…”

Section: Discussionmentioning

confidence: 99%

Treatment features of systemic chemotherapy in young adults with unresectable advanced or recurrent gastric cancer

Nakayama

Chìn

Takahari

et al. 2018

CMAR

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PurposeGastric cancer in young adults (GCYA) is known to have distinct clinicopathological features, including a female predominance and diffuse-type histology. Previous reports have focused on patients who had undergone gastrectomy with curative intent. Information concerning the treatment of unresectable advanced- or recurrent-stage GCYA is lacking. Therefore, we aimed to investigate whether the distinct clinicopathological features of GCYA affect the outcome of systemic chemotherapy.Patients and methodsWe conducted a retrospective cohort study at a single institution in Japan. GCYA was classified as a disease in individuals who were <40 years of age at diagnosis. Initial systemic chemotherapy regimens for GCYA were investigated with a focus on patients who received S-1 plus cisplatin (SP) as a representative standard regimen. The efficacy, safety, and feasibility of systemic chemotherapy were evaluated.ResultsEighty-nine (7.5%) of 1,184 consecutive patients who received systemic chemotherapy at our institute between December 2005 and June 2016 were enrolled. As reported previously, the female sex (57.3%) and diffuse-type histology (91.0%) were the dominant features of GCYA. Thirty-two patients (36.0%) received SP as first-line treatment. The median overall survival and progression-free survival times were 13.2 (95.0% CI: 9.5–18.7) and 5.6 (95.0% CI: 4.7–7.9) months, respectively. The median number of treatment cycles, relative dose intensity, and cumulative dose of cisplatin were 4.5 (range: 1–10), 92.0% (IQR: 83.5–98.3), and 286.5 mg/m2 (IQR: 172.5–367.5), respectively. The most common adverse event of Grade 3 or higher was neutropenia (n=5 patients; 15.6%). No patient had febrile neutropenia. Non-hematological adverse events of Grade 3 or higher were only observed in 2 (6.3%) of 32 patients.ConclusionStandard chemotherapy used for general-aged GC patients has similar efficacy, reduced toxicity, and higher intensity in GCYA patients.

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Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

Cited by 45 publications

References 17 publications

Established fibrous peritoneal metastasis in an immunocompetent mouse model similar to clinical immune microenvironment of gastric cancer

Established fibrous peritoneal metastasis in an immunocompetent mouse model similar to clinical immune microenvironment of gastric cancer

Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

Treatment features of systemic chemotherapy in young adults with unresectable advanced or recurrent gastric cancer

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