Phase II multicenter study of adjuvant S-1 for colorectal liver metastasis: survival analysis of N-SOG 01 trial

Kato, Takehiro; Uehara, K.; Maeda, Atsuyuki; Shimizu, Eiji; Hiramatsu, Kazuhiro; Takeuchi, Eiji; Goto, Hidenari; Tojima, Yuichiro; Yatsuya, Hiroshi; Nagino, Masato

doi:10.1007/s00280-015-2752-5

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…However, the excellent safety profile is contrasted by an inferior therapeutic efficacy. Nevertheless, basing a bacterial therapy along an adjuvant effect alone might prove unfeasible [87–90]. Symbioflor-2 needs to undergo recombinant strengthening to gain efficiency, either by supplementing the bacteria with additional virulence factors and/ or equipping them with expression and secretion systems that ensure delivery of therapeutic molecules to the target tumor.…”

Section: Discussionmentioning

confidence: 99%

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

et al. 2016

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To date, virulent bacteria remain the basis of most bacteria mediated cancer therapies. For clinical application attenuation is required. However, this might result in a drastically lowered therapeutic capacity. Herein we argue that the E. coli probiotic Symbioflor-2, with a history of safe application may constitute a viable tumor therapeutic candidate. We demonstrate that Symbioflor-2 displays a highly specific tumor targeting ability as determined in murine CT26 and RenCa tumor models. The excellent specificity was ascribed to reduced levels of adverse colonization. A high safety standard was demonstrated in WT and Rag1−/− mice. Thus, Symbioflor-2 may represent an ideal tumor targeting delivery system for therapeutic molecules. Moreover, Symbioflor-2 was capable of inducing CT26 tumor clearance as result of an adjuvant effect on tumor specific CD8+ T cells analogous to the Salmonella variant SL7207. However, lower therapeutic efficacy against RenCa tumors suggested a generally reduced therapeutic potency for probiotics. Interestingly, concurrent depletion of Gr-1+ or Ly6G+ cells installed therapeutic efficacy equal to SL7207, thus highlighting the role of innate effector cells in restraining the anti-tumor effects of Symbioflor-2. Collectively, our findings argue for a strategy of safe strain application and a more sustainable use of bacteria as a delivery system for therapeutic molecules.

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Section: Discussionmentioning

confidence: 99%

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

et al. 2016

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“…The results were promising and support a further evaluation of irinotecan-based adjuvant chemotherapy after liver metastasectomy of CRM. The role of a 12-month S-1 scheme, an oral combination of tegafur and two enzyme inhibitors (gimeracil and oteracil), as an alternative approach after metastasectomy was explored by Kato et al [ 39 ] in a single-arm phase II clinical trial with 62 patients from 19 hospitals. The study showed promising results in patients with low tumor burden, but no added benefit was noted regarding the patients in the high-risk group for recurrence, namely those with lymph node metastases around the primary site and/or early liver metastasis.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, Nishioka et al [ 38 ] reported that severe toxicities were significantly more frequent in the oxaliplatin group (50.9%) compared to the UFT group (6.8%, p < 0.001), which led to higher adherence in the UFT arm (84.1%, p < 0.001). Neutropenia was the most common hematological toxicity (5%) also among the patients who received the S-1 regimen according to the results of Kato et al [ 39 ]. The most frequent one though was fatigue in 6.7% of cases.…”

Section: Resultsmentioning

confidence: 99%

Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review

Georgilis

Gavriatopoulou

Tsilimigras

et al. 2023

JCM

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The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to collate the currently available data of the agents used in the adjuvant setting in order to define the most optimal therapeutic strategy. A systematic review of the literature was conducted by searching PubMed/Medline and Cochrane library databases. We included studies that evaluated the efficacy, the tolerability and the safety profile of various chemotherapeutic agents that are used as adjuvant treatment after surgical resection of CRLMs. The outcomes of interest were regression-free survival (RFS), disease-free survival (DFS), overall survival (OS) and severe toxicities. From 543 initial articles, 29 publications with 7028 patients were finally included. In general, the results of the eligible studies indicated that adjuvant therapy after resection of CRLMs led to improved RFS/DFS rates, but this benefit did not contribute to a statistically significant prolongation of OS. Moreover, the choice of the therapeutic strategy, namely systematic or regional chemotherapy or the combination of both, did not seem to have a differential impact on patient outcomes. However, these results should be interpreted with caution since the majority of the chosen studies are of low or moderate quality. In this context, further high-quality clinical trials conducted on patient sub-populations with modern therapies are required in order to reduce in-study and between-study heterogeneity and determine which patients are expected to derive the maximum benefit from adjuvant therapy after surgery for CRLMs.

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“…Moreover, with advances in surgical technique and the following extension of the surgical indication, conversion therapy with curative intent was reported to improve survival; 10) however, these studies included both oncologically unresectable and technically borderline resectable, stage IV and metachronous recurrent disease after curative primary resection. Early liver metastasis after curative resection including stage IV disease has been reported to be a worse prognostic factor [11][12][13] . Faron et al reported that 30% of the registered patients had metachronous recurrence in the four large European randomized controlled trials (RCTs) 7) .…”

Section: Introductionmentioning

confidence: 99%

Outcomes of stage IV patients with colorectal cancer treated in a single institution: What is the key to the long-term survival?

Mukai

Uehara

Aiba

et al. 2018

J Anus Rectum Colon

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Abstract:Objectives: The purpose of this study is to summarize our short-and long-term treatment results for stage IV colorectal cancer (CRC) and to clarify the factors predicting the favorable long-term survival. Methods: Between January 2008 and December 2015, 149 consecutive patients with stage IV CRC underwent initial treatment at Nagoya University Hospital. Their clinical and pathological characteristics, the treatment methods used, and the outcomes were retrospectively analyzed. Results: The median observation period was 23 months. All of the primary and metastatic lesions were technically resectable in 74 patients; however, the remaining 75 were judged as initially unresectable. R0/1 resection during the treatment course was achieved in 74 patients (50%). For the cohort as a whole, the 5-year overall survival (OS) rate was 35%. The 5-year OS rate in the R0/1 resection group was 57%, which was significantly better than that of the non-R0/1 resection group (6%, p < 0.001). In the R0/1 resection group, perioperative chemotherapy significantly improved the outcome (5-year OS; 62% vs. 0%, p = 0.03). In the non-R0/1 resection group, primary tumor resection was associated with a significantly higher favorable prognosis (3-year OS; 20.4% vs. 0%, p = 0.026). Moreover, the additional use of molecular targeted drugs significantly improved the survival. In multivariate analysis, the differentiated histologic type, R0/1 resection, and parallel use of molecular targeted drugs remained independent factors of a favorable outcome. Conclusions: The present study suggested that aggressive curative resection with perioperative chemotherapy might improve survival and that primary tumor resection might improve the outcome in the non-R0/1 group.

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Phase II multicenter study of adjuvant S-1 for colorectal liver metastasis: survival analysis of N-SOG 01 trial

Cited by 9 publications

References 27 publications

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review

Outcomes of stage IV patients with colorectal cancer treated in a single institution: What is the key to the long-term survival?

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