Current Development of  Anti-Cancer Drug S-1

Chhetri, P; Giri, Archana; Shakya, Subarna; Sapkota, Binaya; Kc, Pramod

doi:10.7860/jcdr/2016/19345.8776

Cited by 29 publications

(23 citation statements)

References 28 publications

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“…This was a single-center, single-arm, nonrandomized trial. Another limitation of our study was that we did not test the levels of thymidylate synthase (TS), orotate phosphoribosyl-transferase (OPRT) and dihydropyrimidine dehydrogenase (DPD), which were considered potentially being associated with the efficacy and safety of S-1 [ 22 ]. Due to potential difference between Westerners and Asians in pharmacokinetics and pharmacodynamics of S-1, it is recommended that the plasma concentration, and effectiveness and toxicity related biomarkers (TS and DPD) should be monitored and examined if the similar regimen is applied to Western patients [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Nab-paclitaxel plus S-1 in advanced pancreatic adenocarcinoma (NPSPAC): a single arm, single center, phase II trial

et al. 2017

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This single-arm, phase II trial is to investigate efficacy and safety of nab-paclitaxel plus S-1 as first-line treatment in advanced pancreatic cancer. Nab-paclitaxel was administered at 120 mg/m2 intravenously on day 1 and 8, S-1 was given twice a day orally on day 1-14 of each 21-day cycle, for 6 cycles. The primary endpoint was objective response rate (ORR), the secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. The ORR in intent-to-treat population (N=60) by either blinded independent review (BIR) or investigator assessment was 50.0%. Median PFS (mPFS) by BIR and median OS (mOS) were 5.6 months (95%CI, 4.6 to 6.6 m) and 9.4 months (95%CI, 8.0 to 10.8m), respectively. The most common grade 3 or 4 toxicities were leukopenia/neutropenia (35%) and fatigue (8.3%). Subgroup analyses based on BIR showed a remarkable ORR (>70%) was achieved in patients with female gender, ≥ 50% decline from baseline CA19-9, and developed grade 3 or 4 leukopenia/neutropenia. Remarkable survival benefit was statistically significant in female (mPFS: 7.7m, mOS: 18.2m), ≥ 50% decline from baseline CA19-9 (mPFS: 6.8m, mOS: 11.8m), objective responders (mPFS: 6.9m, mOS: 12.2m), and ECOG of 0 at baseline (mPFS: 7.5m, mOS: 16.1m). Nab-paclitaxel plus S-1 showed encouraging ORR and manageable toxicities, which is an effective alternative treatment regimen for advanced pancreatic cancer. (https://clinicaltrials.gov/ number, NCT02124317)

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Section: Discussionmentioning

confidence: 99%

Nab-paclitaxel plus S-1 in advanced pancreatic adenocarcinoma (NPSPAC): a single arm, single center, phase II trial

et al. 2017

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“…CAP is approved for the treatment of colon cancer, metastatic colorectal cancer, and metastatic breast cancer (Pratt, McLeod, Dean, Malheiro, & Rubinstein, ). S‐1 is composed of tegafur combined with 2 modulators of 5‐FU activity, gimeracil, and potassium oxonate (oteracil) and is used for treating gastric, pancreatic, lung, head, neck, and breast carcinomas (Chhetri et al, ; Ter Veer et al, ). The frequency of HFS induced by CAP is 51–78% (Degen et al, ; Miller, Gorcey, & McLellan, ).…”

Section: Introductionmentioning

confidence: 99%

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

Deng

Sun

2018

Phytotherapy Research

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The aims of this study were to evaluate the efficacy of herbal medicine for the prevention and management of hand-foot syndrome (HFS) induced by fluoropyrimidines and to identify herbs associated with HFS alleviation for further research. The PubMed, Cochrane, Springer, China National Knowledge Infrastructure, and Wanfang databases were searched up to May 2017 for randomized controlled trials (RCTs) that evaluated herbal medicine for relieving HFS in patients undergoing fluoropyrimidine-based chemotherapy. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using RevMan 5.3. In total, 35 RCTs (2,668 participants) were included. Meta-analysis showed that the addition of herbal medicine significantly reduced the incidences of all-grade and high-grade HFS. The total effective rate and complete remission rate of HFS patients increased significantly with herbal medicine arm. Further sensitivity analysis identified Paeoniae Radix Alba, Carthami Flos, Cinnamomi Ramulus, and Glycyrrhizae Radix et Rhizoma as being consistently associated with significant reductions in HFS incidence without important heterogeneity. However, the lack of blinding in most studies may have led to overestimation of these effects. More high-quality RCTs and experimental research are needed to confirm and investigate the efficacy of the herbs identified in this study.

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“…CDHP inhibits 5‐fluorourcil degradation in liver, which results in the maintenance of the 5‐fluorourcil concentration in the body. S‐1 is used for therapies for various cancers, such as breast, gastric, and pancreatic cancers . The previous study has reported that S‐1 administration inhibits metastasis of a high lung‐metastatic subline of a basal‐like breast cancer cell line, MDA‐MB‐231, in a mouse xenograft model .…”

Section: Introductionmentioning

confidence: 99%

5‐Chloro‐2,4‐dihydroxypyridine, CDHP, prevents lung metastasis of basal‐like breast cancer cells by reducing nascent adhesion formation

et al. 2018

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A drug for metastasis prevention is necessary. The orally administered anticancer drug S‐1 contributes to cancer therapy. In a mouse xenograft model of metastatic breast cancer from our previous study, the administration of S‐1 inhibited lung metastasis. However, the mechanism of inhibition remains elusive. S‐1 contains 5‐chloro‐2,4‐dihydroxypyridine (CDHP), which does not have the antigrowth activity, but prevents the degradation of 5‐fluorouracil, an anticancer reagent. In this study, we found that CDHP treatment shrinks cell morphology in metastatic basal‐like breast cancer cell lines. Wound healing assays showed reduced cell migration in CDHP‐treated cells. At the molecular level, CDHP treatment reduced the number of nascent adhesions, whereas the number of mature focal adhesions was not changed. These findings indicate that CDHP impairs focal adhesion formation, which results in a reduction in cell migration. For the in vivo metastasis assay, we used a highly lung‐metastatic cell line. We xenografted them into immunodeficient mice, and administered CDHP. To determine whether CDHP prevents metastasis, we measured the weights of harvested lungs. The results showed that the lung weights of the CDHP‐treated animals were not significantly different compared to the no‐tumor controls, whereas the vehicle group showed a number of metastatic foci and an increase in lung weight. These observations indicate that CDHP administration prevents metastasis. This study reveals a novel effect of CDHP for lung metastasis prevention. Our findings may facilitate the establishment of future metastasis prevention therapies.

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Current Development of Anti-Cancer Drug S-1

Cited by 29 publications

References 28 publications

Nab-paclitaxel plus S-1 in advanced pancreatic adenocarcinoma (NPSPAC): a single arm, single center, phase II trial

Nab-paclitaxel plus S-1 in advanced pancreatic adenocarcinoma (NPSPAC): a single arm, single center, phase II trial

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

5‐Chloro‐2,4‐dihydroxypyridine, CDHP, prevents lung metastasis of basal‐like breast cancer cells by reducing nascent adhesion formation

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