The Experts below are selected from a list of 40581 Experts worldwide ranked by ideXlab platform
Jing-qi Feng - One of the best experts on this subject based on the ideXlab platform.
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Comparison of apatinib and Capecitabine (Xeloda) with Capecitabine (Xeloda) in advanced triple-negative breast cancer as third-line therapy: A retrospective study.
Medicine, 2018Co-Authors: Yang Zhou, Yu-wei Wang, Ling Tong, Run-xue Jiang, Lei Xiao, Guang-ju Zhang, Shu-shan Xing, Fang Qian, Jing-qi FengAbstract:The treatment of advanced triple-negative breast cancer, which failed in first-line or second-line therapy, is a significant challenge. We conducted this retrospective study to explore the efficacy and safety of apatinib and Capecitabine as the third-line treatment for advanced triple-negative breast cancer. This retrospective study involved 44 advanced triple-negative breast cancer patients who failed in first-line or second-line therapy in Tangshan People's Hospital from January 2016 to February 2017. Twenty-two patients received apatinib and Capecitabine, while 22 patients were treated with Capecitabine monotherapy as third-line therapy. The progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events were compared between 2 groups. The apatinib and Capecitabine group exhibited a higher PFS than Capecitabine group (P = .001). Meanwhile, ORR and DCR in apatinib and Capecitabine group were better than in Capecitabine group (P = .042; .016). The 2 groups showed no significant difference in adverse events except degree I-II bleeding (P = .021). Both the apatinib and Capecitabine and the Capecitabine regimens revealed good tolerability. The apatinib and Capecitabine regimen can achieve a better efficacy and similar serious adverse events compared with Capecitabine regimen as the third-line treatment for advanced triple-negative breast cancer.
Toshikazu Ikusue - One of the best experts on this subject based on the ideXlab platform.
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Variants of carboxylesterase 1 have no impact on Capecitabine pharmacokinetics and toxicity in Capecitabine plus oxaliplatin treated-colorectal cancer patients
Cancer Chemotherapy and Pharmacology, 2020Co-Authors: Natsumi Matsumoto, Masae Sekido, Yutaro Kubota, Hiroo Ishida, Ryotaro Ohkuma, Takuya Tsunoda, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Toshikazu IkusueAbstract:Purpose Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of Capecitabine. Methods We enrolled postoperative colorectal cancer (CRC) patients administered with adjuvant Capecitabine plus oxaliplatin (CapeOX) and metastatic CRC patients receiving CapeOX. The pharmacokinetic analysis of the first Capecitabine dose (1000 mg/m^2) was done on day 1, and oxaliplatin administration was shifted to day 2. Plasma concentrations of Capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine (5′-DFUR), and 5-FU were analyzed by high-performance liquid chromatography. CES1 polymorphisms (rs3217164, rs2244614, rs2244613, rs7187684, and rs11861118) and the functional CES1 genes ( 1A1 , var1A1 , 1A2 , and pseudo 1A3 ) in their diplotype configurations were analyzed by direct sequencing. Results Thirty-seven patients were enrolled from September 2017 to February 2020. Patients with a higher area under the plasma concentration–time curve to Capecitabine dose ratio (AUC/dose) of 5′-DFUR than its mean showed a higher frequency of overall ≥ grade 3 toxicity and lower relative dose intensity (RDI) of Capecitabine than those with a lower ratio. Higher CES1 activity expressed as a metabolic ratio (AUC of Capecitabine/sum of three AUCs of each metabolite) lower than its mean was associated with higher 5′-DFUR AUC/dose and lower RDI, indicating essential roles of CES1 in Capecitabine activation to produce 5′-DFUR. However, the association between CES1 variants and Capecitabine pharmacokinetics and toxicity was not significant. Conclusion CES1 variants are not associated with Capecitabine pharmacokinetics and toxicity.
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Variants of carboxylesterase 1 have no impact on Capecitabine pharmacokinetics and toxicity in Capecitabine plus oxaliplatin treated-colorectal cancer patients.
Cancer chemotherapy and pharmacology, 2020Co-Authors: Natsumi Matsumoto, Masae Sekido, Yutaro Kubota, Hiroo Ishida, Ryotaro Ohkuma, Takuya Tsunoda, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Toshikazu IkusueAbstract:Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of Capecitabine. We enrolled postoperative colorectal cancer (CRC) patients administered with adjuvant Capecitabine plus oxaliplatin (CapeOX) and metastatic CRC patients receiving CapeOX. The pharmacokinetic analysis of the first Capecitabine dose (1000 mg/m2) was done on day 1, and oxaliplatin administration was shifted to day 2. Plasma concentrations of Capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine (5′-DFUR), and 5-FU were analyzed by high-performance liquid chromatography. CES1 polymorphisms (rs3217164, rs2244614, rs2244613, rs7187684, and rs11861118) and the functional CES1 genes (1A1, var1A1, 1A2, and pseudo 1A3) in their diplotype configurations were analyzed by direct sequencing. Thirty-seven patients were enrolled from September 2017 to February 2020. Patients with a higher area under the plasma concentration–time curve to Capecitabine dose ratio (AUC/dose) of 5′-DFUR than its mean showed a higher frequency of overall ≥ grade 3 toxicity and lower relative dose intensity (RDI) of Capecitabine than those with a lower ratio. Higher CES1 activity expressed as a metabolic ratio (AUC of Capecitabine/sum of three AUCs of each metabolite) lower than its mean was associated with higher 5′-DFUR AUC/dose and lower RDI, indicating essential roles of CES1 in Capecitabine activation to produce 5′-DFUR. However, the association between CES1 variants and Capecitabine pharmacokinetics and toxicity was not significant. CES1 variants are not associated with Capecitabine pharmacokinetics and toxicity.
Xavier Pivot - One of the best experts on this subject based on the ideXlab platform.
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Analysis of overall survival from a phase III study of ixabepilone plus Capecitabine versus Capecitabine in patients with MBC resistant to anthracyclines and taxanes.
Breast Cancer Research and Treatment, 2010Co-Authors: Gabriel Hortobagyi, Xavier Pivot, Henry Gomez, Hyun-cheol Chung, Luis Fein, Valorie Chan, Jacek Jassem, Guillermo Lerzo, Fernando Hurtado De Mendoza, Linda VahdatAbstract:Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with Capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to Capecitabine (Thomas et al. J Clin Oncol 25:5210-5217, 2007). Here, we report the results of overall survival (OS), a secondary efficacy endpoint from the CA163-046 trial. Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were randomized to ixabepilone (40 mg/m(2) intravenously on day 1 of a 21-day cycle) plus Capecitabine (2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle) or Capecitabine alone (2,500 mg/m(2) on the same schedule). Patients receiving ixabepilone plus Capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving Capecitabine alone (HR = 0.9; 95%CI: 077-1.05; P = 0.19). This observed increase in median OS favored the combination; however, the difference was not statistically significant. Predefined subset analyses showed a clinically meaningful increase in OS in KPS 70-80 patients receiving ixabepilone plus Capecitabine (HR = 0.75; 95% CI: 0.58-0.98). Ixabepilone plus Capecitabine did not show a significant improvement in survival compared to Capecitabine alone in patients with MBC resistant to anthracyclines and taxanes. The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70-80 subgroup.
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Phase III randomized trial of sunitinib versus Capecitabine in patients with previously treated HER2-negative advanced breast cancer.
Breast Cancer Research and Treatment, 2010Co-Authors: Carlos Barrios, Mei-ching Liu, Soo Chin Lee, Laurence Vanlemmens, Jean-marc Ferrero, Toshio Tabei, Xavier Pivot, Hiroji Iwata, Kenjiro Aogi, Roberto Lugo-quintanaAbstract:This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with Capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or Capecitabine 1,250 mg/m(2) (1,000 mg/m(2) in patients >65 years) BID on days 1-14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to Capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with Capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than Capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16-1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus Capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with Capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than Capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC.
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Ixabepilone plus Capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment.
Journal of Clinical Oncology, 2007Co-Authors: Eva Thomas, Xavier Pivot, Henry Gomez, Hyun-cheol Chung, Luis Fein, Valorie Chan, Jacek Jassem, Judith Klimovsky, Fernando Hurtado De Mendoza, Mario CamponeAbstract:PURPOSE: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with Capecitabine in this setting. This study was designed to compare ixabepilone plus Capecitabine versus Capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m(2) intravenously on day 1 of a 21-day cycle plus Capecitabine 2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle, or Capecitabine alone 2,500 mg/m(2) on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. RESULTS: Ixabepilone plus Capecitabine prolonged progression-free survival relative to Capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [>/= grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. CONCLUSION: Ixabepilone plus Capecitabine demonstrates superior efficacy to Capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.
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ixabepilone plus Capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment
Journal of Clinical Oncology, 2007Co-Authors: Eva Thomas, Xavier Pivot, Hyun-cheol Chung, Jacek Jassem, Judith Klimovsky, Henry L Gomez, Rubi K Li, Luis Enrique Fein, Valorie F Chan, Fernando Hurtado De MendozaAbstract:Purpose Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with Capecitabine in this setting. This study was designed to compare ixabepilone plus Capecitabine versus Capecitabine alone in anthracycline-pretreated or -resistant and taxaneresistant locally advanced or metastatic breast cancer. Patients and Methods Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m 2 intravenously on day 1 of a 21-day cycle plus Capecitabine 2,000 mg/m 2 orally on days 1 through 14 of a 21-day cycle, or Capecitabine alone 2,500 mg/m 2 on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. Results Ixabepilone plus Capecitabine prolonged progression-free survival relative to Capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P .0003). Objective response rate was also increased (35% v 14%; P .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. Conclusion Ixabepilone plus Capecitabine demonstrates superior efficacy to Capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes. J Clin Oncol 25:5210-5217. © 2007 by American Society of Clinical Oncology
Yang Zhou - One of the best experts on this subject based on the ideXlab platform.
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Comparison of apatinib and Capecitabine (Xeloda) with Capecitabine (Xeloda) in advanced triple-negative breast cancer as third-line therapy: A retrospective study.
Medicine, 2018Co-Authors: Yang Zhou, Yu-wei Wang, Ling Tong, Run-xue Jiang, Lei Xiao, Guang-ju Zhang, Shu-shan Xing, Fang Qian, Jing-qi FengAbstract:The treatment of advanced triple-negative breast cancer, which failed in first-line or second-line therapy, is a significant challenge. We conducted this retrospective study to explore the efficacy and safety of apatinib and Capecitabine as the third-line treatment for advanced triple-negative breast cancer. This retrospective study involved 44 advanced triple-negative breast cancer patients who failed in first-line or second-line therapy in Tangshan People's Hospital from January 2016 to February 2017. Twenty-two patients received apatinib and Capecitabine, while 22 patients were treated with Capecitabine monotherapy as third-line therapy. The progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events were compared between 2 groups. The apatinib and Capecitabine group exhibited a higher PFS than Capecitabine group (P = .001). Meanwhile, ORR and DCR in apatinib and Capecitabine group were better than in Capecitabine group (P = .042; .016). The 2 groups showed no significant difference in adverse events except degree I-II bleeding (P = .021). Both the apatinib and Capecitabine and the Capecitabine regimens revealed good tolerability. The apatinib and Capecitabine regimen can achieve a better efficacy and similar serious adverse events compared with Capecitabine regimen as the third-line treatment for advanced triple-negative breast cancer.
Natsumi Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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Variants of carboxylesterase 1 have no impact on Capecitabine pharmacokinetics and toxicity in Capecitabine plus oxaliplatin treated-colorectal cancer patients
Cancer Chemotherapy and Pharmacology, 2020Co-Authors: Natsumi Matsumoto, Masae Sekido, Yutaro Kubota, Hiroo Ishida, Ryotaro Ohkuma, Takuya Tsunoda, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Toshikazu IkusueAbstract:Purpose Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of Capecitabine. Methods We enrolled postoperative colorectal cancer (CRC) patients administered with adjuvant Capecitabine plus oxaliplatin (CapeOX) and metastatic CRC patients receiving CapeOX. The pharmacokinetic analysis of the first Capecitabine dose (1000 mg/m^2) was done on day 1, and oxaliplatin administration was shifted to day 2. Plasma concentrations of Capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine (5′-DFUR), and 5-FU were analyzed by high-performance liquid chromatography. CES1 polymorphisms (rs3217164, rs2244614, rs2244613, rs7187684, and rs11861118) and the functional CES1 genes ( 1A1 , var1A1 , 1A2 , and pseudo 1A3 ) in their diplotype configurations were analyzed by direct sequencing. Results Thirty-seven patients were enrolled from September 2017 to February 2020. Patients with a higher area under the plasma concentration–time curve to Capecitabine dose ratio (AUC/dose) of 5′-DFUR than its mean showed a higher frequency of overall ≥ grade 3 toxicity and lower relative dose intensity (RDI) of Capecitabine than those with a lower ratio. Higher CES1 activity expressed as a metabolic ratio (AUC of Capecitabine/sum of three AUCs of each metabolite) lower than its mean was associated with higher 5′-DFUR AUC/dose and lower RDI, indicating essential roles of CES1 in Capecitabine activation to produce 5′-DFUR. However, the association between CES1 variants and Capecitabine pharmacokinetics and toxicity was not significant. Conclusion CES1 variants are not associated with Capecitabine pharmacokinetics and toxicity.
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Variants of carboxylesterase 1 have no impact on Capecitabine pharmacokinetics and toxicity in Capecitabine plus oxaliplatin treated-colorectal cancer patients.
Cancer chemotherapy and pharmacology, 2020Co-Authors: Natsumi Matsumoto, Masae Sekido, Yutaro Kubota, Hiroo Ishida, Ryotaro Ohkuma, Takuya Tsunoda, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Toshikazu IkusueAbstract:Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of Capecitabine. We enrolled postoperative colorectal cancer (CRC) patients administered with adjuvant Capecitabine plus oxaliplatin (CapeOX) and metastatic CRC patients receiving CapeOX. The pharmacokinetic analysis of the first Capecitabine dose (1000 mg/m2) was done on day 1, and oxaliplatin administration was shifted to day 2. Plasma concentrations of Capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine (5′-DFUR), and 5-FU were analyzed by high-performance liquid chromatography. CES1 polymorphisms (rs3217164, rs2244614, rs2244613, rs7187684, and rs11861118) and the functional CES1 genes (1A1, var1A1, 1A2, and pseudo 1A3) in their diplotype configurations were analyzed by direct sequencing. Thirty-seven patients were enrolled from September 2017 to February 2020. Patients with a higher area under the plasma concentration–time curve to Capecitabine dose ratio (AUC/dose) of 5′-DFUR than its mean showed a higher frequency of overall ≥ grade 3 toxicity and lower relative dose intensity (RDI) of Capecitabine than those with a lower ratio. Higher CES1 activity expressed as a metabolic ratio (AUC of Capecitabine/sum of three AUCs of each metabolite) lower than its mean was associated with higher 5′-DFUR AUC/dose and lower RDI, indicating essential roles of CES1 in Capecitabine activation to produce 5′-DFUR. However, the association between CES1 variants and Capecitabine pharmacokinetics and toxicity was not significant. CES1 variants are not associated with Capecitabine pharmacokinetics and toxicity.
