Yuichi Ando

Nagoya University, Nagoya, Aichi, Japan

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Publications (89)347.44 Total impact

  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 12/2014;
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    ABSTRACT: Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear.
    Breast cancer (Tokyo, Japan). 07/2014;
  • Tomoya Shimokata, Yuichi Ando
    The Lancet Oncology 06/2014; 15(7):e249-50. · 25.12 Impact Factor
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    ABSTRACT: PurposeIn Japan, biological safety cabinets are commonly used by medical staff to prepare antineoplastic agents. At the Division of Chemotherapy for Outpatients, Nagoya University Hospital, a class II B2 biological safety cabinet is used. The temperature inside this biological safety cabinet decreases in winter. In this study, we investigated the effect of low outside air temperature on the biological safety cabinet temperature, time required to admix antineoplastic agents, and accuracy of epirubicin weight measurement. /st>Studies were conducted from 1 January to 31 March 2008 (winter). The outside air temperature near the biological safety cabinet intake nozzle was compared with the biological safety cabinet temperature. The correlation between the outside air temperature and the biological safety cabinet temperature, time for cyclophosphamide and gemcitabine solubilization, and accuracy of epirubicin weight measurement were investigated at low and high biological safety cabinet temperatures. /st>The biological safety cabinet temperature correlated with the outside air temperature of 5-20 (p < 0.0001). Compared to cyclophosphamide and gemcitabine solubilization in the biological safety cabinet at 25, solubilization at 10 was significantly delayed (p < 0.01 and p < 0.0001, respectively). Measurement of epirubicin weight by using a syringe lacked accuracy because of epirubicin's high viscosity at low temperatures (p < 0.01). /st>These results suggest that the biological safety cabinet temperature decreases when cool winter air is drawn into the biological safety cabinet, affecting the solubilization of antineoplastic agents. We suggest that a decrease in biological safety cabinet temperature may increase the time required to admix antineoplastic agents, thereby increasing the time for which outpatients must wait for chemotherapy.
    Journal of Oncology Pharmacy Practice 04/2014;
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    ABSTRACT: Carboplatin is a platinum-based anticancer drug that has been long used to treat many types of solid cancer. Because the clearance of carboplatin strongly correlates with the glomerular filtration rate (GFR), its dosage is calculated with the Calvert formula on the basis of the patient's GFR to achieve the target area under the plasma drug concentration-time curve (AUC) for each patient. However, many lines of evidence from previous clinical studies should be interpreted with caution because different methods were used to estimate drug clearance and derive the dosage of carboplatin. There is a particularly high risk of carboplatin overdosing when the dosage is determined on the basis of standardized serum creatinine values. When deciding the dose of carboplatin for adult Japanese patients, preferred methods to assess renal function instead of directly measuring GFR include (1) 24-h urinary collection-based creatinine clearance adjusted by adding 0.2 mg/dl to the serum creatinine concentration measured by standardized methods, and (2) equation-based GFR (eGFR) with a back calculation to units of ml/min per subject. Given the limitations of serum creatinine-based GFR estimations, the GFR or creatinine clearance should be directly measured in each patient whenever possible. To ensure patient safety and facilitate a medical-team approach, the single most appropriate method available at each institute or medical team should be consistently used to calculate the dose of carboplatin with the Calvert formula.
    Nagoya journal of medical science 02/2014; 76(1-2):1-9.
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    ABSTRACT: A phase 1 study of pazopanib alone or in combination with lapatinib was conducted to assess the safety, tolerability, and pharmacokinetics of these oral tyrosine kinase inhibitors in Japanese patients with solid tumors. In part A (monotherapy), 7 patients initially received pazopanib 800 mg/day, the recommended dose for non-Japanese patients. Then, 3 patients received pazopanib 400 mg/day on day 1 followed by 800 mg/day from day 2 onward. Three other patients received pazopanib 1,000 mg/day. In part B (combination therapy), 17 patients received pazopanib plus lapatinib (pazopanib/lapatinib) at once-daily doses of 400/1,000 mg (4 patients), 800/1,000 mg (3 patients), 400/1,500 mg (3 patients), and then 600/1,250 mg (7 patients). There was no dose-limiting toxicity during the study. In part A, most drug-related adverse events were grade 2 or lower, including neutropenia/neutrophil count decreased, thrombocytopenia/platelet count decreased, diarrhea, hypertension, aspartate aminotransferase increased, and lipase increased. In part B, rash, decreased appetite, and serum thyroid-stimulating hormone increased also occurred. In all dose groups, the plasma concentrations after multiple doses of pazopanib exceeded the target trough concentration for inhibition of vascular endothelial growth factor receptor-2 activity (20 μg/mL). The pharmacokinetic profiles of pazopanib and lapatinib in Japanese patients were not apparently different from those reported in non-Japanese patients. There were no consistent trends in pharmacokinetic drug interactions between pazopanib and lapatinib. Pazopanib monotherapy at 800 and 1,000 mg once daily and pazopanib plus lapatinib once daily at any doses studied were well tolerated in Japanese patients.
    Cancer Chemotherapy and Pharmacology 01/2014; · 2.80 Impact Factor
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    ABSTRACT: Buparlisib (BKM120) is an oral pan-phosphatidylinositol 3-kinase inhibitor, targeting all four isoforms of class I PI3K (α, β, γ, and δ). This open-label, Phase I, dose-escalation study was conducted to determine the maximum tolerated dose of continuous daily buparlisib in Japanese patients with advanced solid tumors. Secondary objectives included safety and tolerability, pharmacokinetics, antitumor activity, and pharmacodynamic marker changes. Fifteen patients were treated at 25 mg/day (n=3), 50 mg/day (n=3), and 100 mg/day (n=9) dose levels. One dose-limiting toxicity of Grade 4 abnormal liver function occurred at 100 mg/day. Considering the safety profile and the maximum tolerated dose in the first-in-man study of buparlisib in non-Japanese patients, further dose escalation was stopped and 100 mg/day was declared the recommended dose. Most common treatment-related adverse events included rash, abnormal hepatic function (including increased transaminase levelss), increased blood insulin levels, and increased eosinophil count. Hyperglycemia was experienced by two patients, one each Grade 1 and 4, and mood alterations were experienced by three patients, two Grade 1 and one Grade 2. Pharmacokinetic results showed buparlisib was rapidly absorbed in a dose-proportional manner. Best overall response was stable disease for six patients, including one unconfirmed partial response. In these Japanese patients with advanced solid tumors, buparlisib had a manageable safety profile, with similar pharmacokinetics to non-Japanese patients. The recommended dose of 100 mg/day will be used in future studies of buparlisib in Japanese patients.(www.clinicaltrials.gov; NCT01283503) This article is protected by copyright. All rights reserved.
    Cancer Science 01/2014; · 3.48 Impact Factor
  • 01/2014; 15(8):e299–e300.
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    ABSTRACT: Attempts have been made to use bevacizumab (BEV) in an adjuvant or neoadjuvant setting. However, BEV is known to cause various adverse events, and the safety of neoadjuvant BEV has not yet been fully evaluated. This study assessed the postoperative complications in patients receiving neoadjuvant BEV for colorectal cancer. The data for 78 patients with resectable advanced or metastatic colorectal cancer who received neoadjuvant BEV followed by surgical resection were retrospectively analyzed. The median interval between the last BEV dose and surgery was 9 weeks. The most common postoperative complication was pelvic sepsis, which occurred in 11 patients (14 %). A biliary fistula developed in four of 23 patients who underwent liver resection. Anastomotic leakage occurred in six of 24 patients with a colorectal anastomosis, four of whom required re-laparotomy. In a univariate analysis, male gender and a greater intraoperative blood loss were associated with postoperative complications of any grade. Colorectal anastomosis was a risk factor for major complications. In a multivariate analysis, intraoperative blood loss was an independent risk factor for postoperative complications of any grade (HR 6.338; P = 0.003). With regard to major postoperative complications, colorectal primary anastomosis was the only independent predictive risk factor (HR 8.285; P = 0.013). In patients with colorectal cancer who underwent elective surgery after BEV treatment, the interval between BEV and surgery was not a risk factor for postoperative complications (based on a median interval of 9 weeks). Colorectal primary anastomosis was the only independent risk factor for major postoperative complications.
    Surgery Today 08/2013; · 0.96 Impact Factor
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    ABSTRACT: BACKGROUND: Nilotinib is a BCR-ABL kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (CML). The UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphism UGT1A1*28 (*28)/*28 has been linked to an increased risk of hyperbilirubinemia in patients with CML who receive nilotinib. Beside *28, UGT1A1*6 (*6) is another important variant allele in Japanese patients because it is associated with adverse events of irinotecan, metabolized by UGT1A1. We retrospectively investigated the association between severe toxicity of nilotinib and UGT1A1 polymorphisms (*6 and*28) in Japanese patients with CML. PATIENTS AND METHODS: Eight patients with cytogenetically confirmed CML who were receiving nilotinib were studied to explore the association of UGT1A1 polymorphisms with severe nilotinib-related toxicity. Genotyping analyses were determined for *6 and *28. RESULTS: All 3 patients with the *6/*6 or *6/*28 genotype had severe toxicity, including QT interval prolongation (grade 3), elevated lipase levels (grade 3) plus hyperbilirubinemia (grade 2), and anemia (grade 3) plus hepatic cyst hemorrhage (grade 2) in 1 patient each. Among the 5 patients with the *6/*1 or *1/*1 genotype, 1 had elevated lipase levels (grade 3) and another had severe pain in the lower extremities (grade 3). CONCLUSION: These findings suggest that UGT1A1 polymorphisms are important determinants of severe toxicity of nilotinib in Japanese patients.
    International Journal of Clinical Oncology 04/2013; · 1.41 Impact Factor
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    ABSTRACT: Objective: Pharmacogenomic associations between severe oxaliplatininduced chronic peripheral neurotoxicity (OXCPN) (Grade 2 lasting for > 7 days or Grade 3) and 9 single nucleotide polymorphisms (SNPs) in 8 genes (TAC1, FOXC1, ITGA1, ACYP2, DLEU7, BTG4, CAMK2N1, and FARS2) were reported by the genomewide association study (GWAS) in Korean patients. The present study was designed to explore reliable predictors of OXCPN and thereby improve the management of metastatic colorectal cancer (CRC). Methods: We retrospectively investigated pharmacogenomic characteristics of OXCPN in 70 Japanese patients with CRC who received oxaliplatin-based chemotherapy and updated the results of our previous analysis of ERCC1 (C118T, rs11615 and C8092A, rs3212986) and GSTP1 (Ile105Val, rs1695) polymorphisms. Results: Univariate analysis suggested potential associations of severe OXCPN with rs843748 in ACYP2 and rs17140129 in FARS2, as well as with the absence of diabetes mellitus (DM) (p = 0.056, 0.072, and 0.029, respectively). There was no association between severe OXCPN and any of the 7 other SNPs. Multiple logistic regression analysis showed that an increased risk of severe OXCPN was related to rs17140129 and the absence of DM (p = 0.034 and 0.030, respectively). On updated analysis, polymorphisms of ERCC1 (C118T, rs11615) and rs10486003 in TAC1 were associated with time to the onset of Grade 1 OXCPN (p = 0.024 and 0.049, respectively). Conclusions: Severe OXCPN is significantly related to rs17140129, found in the GWAS of Korean patients, in Japanese patients. Patients without DM are more likely to have OXCPN. The association between ERCC1 polymorphism and time to the onset of OXCPN was significant on updated analysis.
    International journal of clinical pharmacology and therapeutics 04/2013; · 1.20 Impact Factor
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    ABSTRACT: PURPOSE: This phase I study was designed to determine the maximum tolerated dose (MTD) and the dose to be recommended for a future phase II study of tasisulam sodium in Japanese patients with advanced, refractory solid tumors. Safety, pharmacokinetics and preliminary anti-tumor activities were assessed. Due to high-affinity albumin binding, an albumin-tailored dose to reduce the variability in tasisulam exposure was also studied. METHODS: A dose escalation scheme of tasisulam was used over 4 dose levels. Dose levels 1-3 targeted the maximum plasma concentration (C (max)) of 300, 340, and 360 μg/mL. Dose level 4 used an albumin-tailored range of C (max)-targeted doses to achieve an albumin-corrected exposure (AUCalb) of 1,200-6,400 μg h/mL, the range chosen for global tasisulam studies. Tasisulam was administered intravenously on day 1 of each 21-day (dose levels 1 and 2) or 28-day (dose levels 3 and 4) cycle. RESULTS: The major adverse events were related to bone marrow suppression, particularly neutropenia and thrombocytopenia. Dose-limiting toxicities (DLTs) were not observed until dose level 4, where 3 out of 6 patients experienced DLT, despite a tendency toward lower AUCalb variability (CV %) in the albumin-tailored dose group (38 %) compared with the targeted C (max) groups (50-236 %). CONCLUSIONS: Tasisulam in doses up to dose level 3 (target C (max) 360 μg/mL) was well tolerated. Although albumin-tailored dosing provided less AUCalb variability, a MTD that aligns with other global tasisulam studies was not identified. A lower AUCalb range may be required for the Japan population.
    Cancer Chemotherapy and Pharmacology 02/2013; · 2.80 Impact Factor
  • Ayako Mitsuma, Yuichi Ando
    Folia Pharmacologica Japonica 02/2013; 141(2):62-5.
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    ABSTRACT: PURPOSE: Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy. METHODS: We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure. RESULTS: The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension. CONCLUSIONS: This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy.
    Cancer Chemotherapy and Pharmacology 11/2012; · 2.80 Impact Factor
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    ABSTRACT: This pharmacokinetic study of S-1 was conducted in patients in whom glomerular filtration rate (GFR) was directly measured to explore the possibility of adjusting the S-1 dose on the basis of GFR in patients with normal or nearly normal renal function. S-1 was given to 12 patients twice daily for 28 consecutive days followed by 14 days of rest, repeated every 6 weeks. GFR was measured on the basis of inulin clearance (CLin) before the first day of treatment. The area under the time-concentration curve (AUC) of 5-fluorouracil (5-FU) correlated with that of 5-chloro-2,4-dihydroxypyridine (CDHP, r = 0.750, p = 0.005). The AUC of CDHP correlated with the measured 24-hour creatinine clearance (CLcr) per subject (r = -0.620, p = 0.032), but not with the CLin (r = -0.356, p = 0.257). The AUC of 5-FU did not correlate with either the 24-hour CLcr per subject (r = -0.401, p = 0.187) or with the CLin (r = -0.300, p = 0.351). Dosage adjustment based on the GFR does not reduce individual variations in 5-FU concentrations among patients with normal or nearly normal renal function who receive S-1.
    Oncology 06/2012; 83(1):38-44. · 2.17 Impact Factor
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    ABSTRACT: A massive extravasation of pegylated-liposomal doxorubicin (Doxil) accidentally occurred, affecting the right forearm of a 54-year-old woman with metastatic ovarian cancer who was receiving an intravenous infusion of the drug. In accordance with the institutional guidelines for vesicant drugs, a corticosteroid preparation was immediately injected subcutaneously into the surrounding tissues. Clobetasol propionate and an ice pack were then topically applied to the affected region. There were no serious complications at the extravasation site, such as tissue necrosis or severe pain, and only a transient erythema of the skin and desquamation remained after 2 months.
    Nagoya journal of medical science 02/2012; 74(1-2):189-92.
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    ABSTRACT: Purpose Sagopilone has recently been identified and preferentially used for the treatment of taxane-resistant cancer. The purpose of this dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics (PK) of sagopilone in refractory solid tumors. Methods A total of 17 Japanese patients received sagopilone in this Phase I study. Sagopilone was given as a 30-min intravenous infusion once every 3 weeks (one course) with an initial dose of 12.4 mg/m(2) up to 22.0 mg/m(2) for a maximum of 6 courses. Results The maximum tolerated dose (MTD) was determined to be 16.5 mg/m(2). The major dose-limiting toxicity (DLT) was peripheral sensory neuropathy. The PK data demonstrated that sagopilone did not accumulate after repeated administration. Two patients had stable disease (SD) over a period of 12 weeks. Conclusions Our study demonstrated clinically favorable safety, tolerability, and efficacy of sagopilone, which will help define the treatment of advanced tumors in more extensive clinical trials.
    Investigational New Drugs 12/2011; · 3.50 Impact Factor
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    ABSTRACT: Panobinostat (LBH589) is a potent pan-histone deacetylase inhibitor. As a result of promising preclinical data, Phase I and II clinical trials of intravenous and oral panobinostat have been conducted in patients with a wide variety of hematologic and solid tumors. This is the first report of a phase I study to evaluate intravenous panobinostat given on days 1 and 8 of a 21-day cycle in patients with solid tumors. The primary objective was to characterize the safety and tolerability of panobinostat by evaluating the occurrence of dose-limiting toxicity (DLT) and determining the maximum tolerated dose (MTD) in Japanese patients with advanced solid tumors. Secondary objectives included characterizing the pharmacokinetics and assessing antitumor activity. Fourteen patients were assigned to three dose levels (Cohort 1: 10 mg/m(2) [three patients], Cohort 2: 15 mg/m(2) [three patients], Cohort 3: 20 mg/m(2) [eight patients]), according to a standard "3 + 3" design. One patient who received 20 mg/m(2) had a DLT (grade 3 elevation of γ-glutamyl transpeptidase for >7 days). Thrombocytopenia was observed in all patients (grade 3 or 4 in 8), the severity of which was dependent on the dose and platelet count at baseline. The thrombocytopenia rapidly resolved within 8 days. Plasma panobinostat levels increased dose dependently, without clinically significant drug accumulation. Stable disease for ≥4 months was observed in six patients; however, there were no complete or partial responses. It is feasible to conclude that 20 mg/m(2) was the MTD and recommend as the starting dose for phase II clinical trials.
    Investigational New Drugs 10/2011; 30(5):1950-7. · 3.50 Impact Factor
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    ABSTRACT: Corrected QT (QTc) interval prolongation can induce fatal arrhythmias such as torsade de pointes. To assess the characteristics of QTc intervals and arrhythmias in women with early breast cancer who received FEC100 adjuvant chemotherapy, electrocardiograms (ECGs) were recorded before and after each chemotherapy. Associations between QTc interval prolongation and single nucleotide polymorphisms (SNPs) of potassium channel genes were also investigated. A total of 131 ECG records were obtained in 34 patients who received 153 cycles of FEC100. QTc intervals could be measured in 127 records. There was a significant trend toward QTc interval prolongation after each treatment, persisting through four cycles of chemotherapy (P < 0.001). Median QTc interval prolongations were 13, 11, 18, and 14 ms in the first through fourth cycles of chemotherapy, respectively. QTc intervals differed significantly between cycles 1 and 4 before treatment as well as after treatment (P < 0.05). A single supraventricular premature contraction was noted in 3 (2.3%) of the 131 cycles in 2 (5.9%) of the 34 patients. There was no significant association between QTc interval prolongation and SNPs of potassium channel genes. This prospective study confirmed that FEC100 is associated with significant QTc interval prolongation in women with early breast cancer.
    Annals of Oncology 06/2011; 23(3):743-7. · 7.38 Impact Factor
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    ABSTRACT: We examined the feasibility of regimen selection for first-line irinotecan, 5-fluorouracil and leucovorin or oxaliplatin, 5-fluorouracil and leucovorin in Japanese patients with advanced colorectal cancer based on UDP-glucuronosyltransferase 1A1 genotype as well as physical status of patients related to diarrhea. As first-line irinotecan, 5-fluorouracil and leucovorin is a little bit superior to oxaliplatin, 5-fluorouracil and leucovorin with respect to efficacy and toxicity, patients without risk factors of irinotecan-induced toxicity were first assigned to irinotecan, 5-fluorouracil and leucovorin. Patients with UDP-glucuronosyltransferase 1A1 28/ 28, 6/ 6, 28/ 6 or 28/ 27 and those with ascites, peritoneal dissemination or diarrhea first received oxaliplatin, 5-fluorouracil and leucovorin to avoid the irinotecan-induced neutropenia and diarrhea, respectively. We retrospectively evaluated the feasibility of this strategy by assessing toxicity and total progression-free survival in first- and subsequent second-line therapies in all patients studied. In the first-line irinotecan, 5-fluorouracil and leucovorin (n = 61), Grade 4 neutropenia, febrile neutropenia and Grade 3 diarrhea occurred in 8.2, 3.3 and 3.3% of patients, respectively. In the first-line oxaliplatin, 5-fluorouracil and leucovorin (n = 26), Grade 4 neutropenia, febrile neutropenia, Grade 3 thrombocytopenia and Grade 3 neuropathy were observed in 11.5, 3.8, 3.8 and 7.7% of patients, respectively. In the second-line oxaliplatin, 5-fluorouracil and leucovorin (n = 38), Grade 3 diarrhea occurred in 2.6% of patients. In the second-line irinotecan monotherapy (n = 11), Grade 4 or febrile neutropenia occurred in 18% of patients and Grade 3 diarrhea in 9.1% of patients. In second-line S-1 (n = 9), Grade 3 anemia occurred in 2 patients. Median total progression-free survival in all 87 patients was 11.5 months. Present regimen selection strategy would be feasible, since it causes less toxicity and similar efficacy comparing to previous studies. Determination of appropriate reduced dose in the second-line irinotecan monotherapy or other standard second-line therapy for patients with high-risk to irinotecan-induced toxicity might make this strategy more effective.
    Japanese Journal of Clinical Oncology 02/2011; 41(5):617-23. · 1.90 Impact Factor

Publication Stats

2k Citations
347.44 Total Impact Points

Institutions

  • 1998–2014
    • Nagoya University
      • • Division of Clinical Oncology and Chemotherapy
      • • Division of of Internal Medicine
      Nagoya, Aichi, Japan
    • Hokkaido University
      • Faculty of Pharmaceutical Sciences
      Sapporo-shi, Hokkaido, Japan
  • 2005–2011
    • Saitama Medical University
      • • Department of Internal Medicine
      • • Department of Medical Oncology
      Saitama, Saitama-ken, Japan
  • 2002
    • National Institutes of Health
      Maryland, United States
  • 2001
    • Japanese Red Cross
      Edo, Tōkyō, Japan
  • 1993–1999
    • Nagoya Second Red Cross Hospital
      Nagoya, Aichi, Japan
  • 1996
    • The University of Chicago Medical Center
      • Department of Medicine
      Chicago, IL, United States