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T Hirashima - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety analysis according to histology for s 1 in combination with Carboplatin as first line chemotherapy in patients with advanced non small cell lung cancer updated results of the west japan oncology group lets study
Annals of Oncology, 2013Co-Authors: Hiroshige Yoshioka, Isamu Okamoto, Satoshi Morita, M Ando, Koji Takeda, Takashi Seto, Noboru Yamamoto, Hideo Saka, Shinji Atagi, T HirashimaAbstract:Background: A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for Carboplatin–S-1 compared with Carboplatin–paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Patients and methods: A total of 564 patients were randomly assigned to receive either Carboplatin on day 1 plus oral S-1 on days 1–14 or Carboplatin–paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented. Results: The updated analysis revealed a median OS of 15.2 months in the Carboplatin–S-1 arm and 13.1 months in the Carboplatin–paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793–1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the Carboplatin–S-1 arm and 10.6 months in the Carboplatin–paclitaxel arm (HR 0.713; 95% CI 0.476–1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859–1.308) for those with non-SCC. Conclusions: These results establish the efficacy and safety of Carboplatin–S-1 in patients with advanced NSCLC regardless of tumor histology.
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phase iii trial comparing oral s 1 plus Carboplatin with paclitaxel plus Carboplatin in chemotherapy naive patients with advanced non small cell lung cancer results of a west japan oncology group study
Journal of Clinical Oncology, 2010Co-Authors: Isamu Okamoto, Hiroshige Yoshioka, Satoshi Morita, M Ando, Koji Takeda, Takashi Seto, Hideo Saka, Nobuyuki Yamamoto, Kazuhiro Asami, T HirashimaAbstract:Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with Carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with Carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either Carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or Carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of Carboplatin and S-1 compared with Carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the Carboplatin and S-1 arm and ...
Yoshikazu Higami - One of the best experts on this subject based on the ideXlab platform.
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Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways
International Journal of Molecular Sciences, 2019Co-Authors: Kanako Miyano, Miki Nonaka, Seiji Shiraishi, Toru Yokoyama, Kiyoshi Terawaki, Hiroaki Murata, Koichiro Minami, Masami Suzuki, Yuka Sudo, Yoshikazu HigamiAbstract:Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is not only involved in pain transmission, but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on Carboplatin-induced PN is unclear. We revealed that Carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in Carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, Carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, Carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and Carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased the Carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved Carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that Carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.
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Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways
2019Co-Authors: Kanako Miyano, Miki Nonaka, Seiji Shiraishi, Toru Yokoyama, Kiyoshi Terawaki, Hiroaki Murata, Koichiro Minami, Masami Suzuki, Yuka Sudo, Yoshikazu HigamiAbstract:Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is involved not only in pain transmission but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on Carboplatin-induced PN is unclear. We revealed that Carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in Carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, Carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, Carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and Carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased Carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved Carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that Carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.
Isamu Okamoto - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety analysis according to histology for s 1 in combination with Carboplatin as first line chemotherapy in patients with advanced non small cell lung cancer updated results of the west japan oncology group lets study
Annals of Oncology, 2013Co-Authors: Hiroshige Yoshioka, Isamu Okamoto, Satoshi Morita, M Ando, Koji Takeda, Takashi Seto, Noboru Yamamoto, Hideo Saka, Shinji Atagi, T HirashimaAbstract:Background: A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for Carboplatin–S-1 compared with Carboplatin–paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Patients and methods: A total of 564 patients were randomly assigned to receive either Carboplatin on day 1 plus oral S-1 on days 1–14 or Carboplatin–paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented. Results: The updated analysis revealed a median OS of 15.2 months in the Carboplatin–S-1 arm and 13.1 months in the Carboplatin–paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793–1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the Carboplatin–S-1 arm and 10.6 months in the Carboplatin–paclitaxel arm (HR 0.713; 95% CI 0.476–1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859–1.308) for those with non-SCC. Conclusions: These results establish the efficacy and safety of Carboplatin–S-1 in patients with advanced NSCLC regardless of tumor histology.
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thymidylate synthase and dihydropyrimidine dehydrogenase expression levels are associated with response to s 1 plus Carboplatin in advanced non small cell lung cancer
Lung Cancer, 2011Co-Authors: Masayuki Takeda, Isamu Okamoto, Naoko Hirabayashi, Mami Kitano, Kazuhiko NakagawaAbstract:Abstract S-1 is an oral fluoropyrimidine derivative that is active against non-small cell lung cancer (NSCLC). Development of S-1 combination chemotherapy for advanced NSCLC is under way. Given the importance of designing therapeutic strategies based on specific tumor biology, we have evaluated the relation between immunohistochemical expression levels of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), or dihydropyrimidine dehydrogenase (DPD) and the response to treatment with S-1 plus Carboplatin in patients with advanced NSCLC. Chemotherapy-naive patients with advanced (stage IIIB or IV) NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and archival tumor tissue were assigned to receive S-1–Carboplatin ( n = 22). The predictive or prognostic relevance of the molecular markers was also examined by their evaluation in patients treated with paclitaxel plus Carboplatin ( n = 25). Expression levels of TS, OPRT, or DPD in tumor specimens did not differ significantly between patients treated with S-1–Carboplatin and those treated with paclitaxel–Carboplatin. A low expression level of TS or of DPD was associated with a better response and longer survival in patients treated with S-1–Carboplatin but not in those treated with paclitaxel–Carboplatin. Tumor expression levels of TS and DPD are predictive of response to S-1–Carboplatin chemotherapy in patients with advanced NSCLC.
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phase iii trial comparing oral s 1 plus Carboplatin with paclitaxel plus Carboplatin in chemotherapy naive patients with advanced non small cell lung cancer results of a west japan oncology group study
Journal of Clinical Oncology, 2010Co-Authors: Isamu Okamoto, Hiroshige Yoshioka, Satoshi Morita, M Ando, Koji Takeda, Takashi Seto, Hideo Saka, Nobuyuki Yamamoto, Kazuhiro Asami, T HirashimaAbstract:Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with Carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with Carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either Carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or Carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of Carboplatin and S-1 compared with Carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the Carboplatin and S-1 arm and ...
Pamela A. Hershberger - One of the best experts on this subject based on the ideXlab platform.
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Vorinostat increases Carboplatin and paclitaxel activity in non‐small cell lung cancer cells
International journal of cancer, 2010Co-Authors: Taofeek K. Owonikoko, Suresh S. Ramalingam, Beatriz Kanterewicz, Trent E. Balius, Chandra P. Belani, Pamela A. HershbergerAbstract:We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/Carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to Carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 µM) synergistically increased the growth inhibitory effects of Carboplatin/paclitaxel in 128-88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of Carboplatin but not paclitaxel. The % colony formation was: control 100%; 1 µM vorinostat 83% ± 10%; 5 µM Carboplatin, 41% ± 11%; Carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat 46% ± 21%. In A549 and 128-88T, vorinostat potentiated Carboplatin induction of gamma-H2AX (a DNA damage marker) and increased α-tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in α-tubulin acetylation, which reversed upon drug wash-out. We conclude that vorinostat interacts favorably with Carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat-mediated irreversible increase in DNA damage in the case of Carboplatin and a reversible increase in microtubule stability in the case of paclitaxel.
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vorinostat increases Carboplatin and paclitaxel activity in non small cell lung cancer cells
International Journal of Cancer, 2010Co-Authors: Taofeek K. Owonikoko, Suresh S. Ramalingam, Beatriz Kanterewicz, Trent E. Balius, Chandra P. Belani, Pamela A. HershbergerAbstract:We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/Carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to Carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 µM) synergistically increased the growth inhibitory effects of Carboplatin/paclitaxel in 128-88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of Carboplatin but not paclitaxel. The % colony formation was: control 100%; 1 µM vorinostat 83% ± 10%; 5 µM Carboplatin, 41% ± 11%; Carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat 46% ± 21%. In A549 and 128-88T, vorinostat potentiated Carboplatin induction of gamma-H2AX (a DNA damage marker) and increased α-tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in α-tubulin acetylation, which reversed upon drug wash-out. We conclude that vorinostat interacts favorably with Carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat-mediated irreversible increase in DNA damage in the case of Carboplatin and a reversible increase in microtubule stability in the case of paclitaxel.
Hiroshige Yoshioka - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety analysis according to histology for s 1 in combination with Carboplatin as first line chemotherapy in patients with advanced non small cell lung cancer updated results of the west japan oncology group lets study
Annals of Oncology, 2013Co-Authors: Hiroshige Yoshioka, Isamu Okamoto, Satoshi Morita, M Ando, Koji Takeda, Takashi Seto, Noboru Yamamoto, Hideo Saka, Shinji Atagi, T HirashimaAbstract:Background: A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for Carboplatin–S-1 compared with Carboplatin–paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Patients and methods: A total of 564 patients were randomly assigned to receive either Carboplatin on day 1 plus oral S-1 on days 1–14 or Carboplatin–paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented. Results: The updated analysis revealed a median OS of 15.2 months in the Carboplatin–S-1 arm and 13.1 months in the Carboplatin–paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793–1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the Carboplatin–S-1 arm and 10.6 months in the Carboplatin–paclitaxel arm (HR 0.713; 95% CI 0.476–1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859–1.308) for those with non-SCC. Conclusions: These results establish the efficacy and safety of Carboplatin–S-1 in patients with advanced NSCLC regardless of tumor histology.
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phase iii trial comparing oral s 1 plus Carboplatin with paclitaxel plus Carboplatin in chemotherapy naive patients with advanced non small cell lung cancer results of a west japan oncology group study
Journal of Clinical Oncology, 2010Co-Authors: Isamu Okamoto, Hiroshige Yoshioka, Satoshi Morita, M Ando, Koji Takeda, Takashi Seto, Hideo Saka, Nobuyuki Yamamoto, Kazuhiro Asami, T HirashimaAbstract:Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with Carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with Carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either Carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or Carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of Carboplatin and S-1 compared with Carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the Carboplatin and S-1 arm and ...