Publications by authors named "Hiroo Ishida"

Background: Pembrolizumab monotherapy significantly extends progression-free and overall survival compared to platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC), but also has a significant impact on medical costs.

Aim: To clarify the health economic evidence for selecting the first-line treatment for patients with stage IV advanced NSCLC with a programmed cell death ligand 1 tumor proportion score of 50% or greater in Japan, we assessed the cost-effectiveness of pembrolizumab monotherapy compared with that of platinum-based chemotherapy.

Method: Using a Markov model, the study simulated three health states for patients, based on clinical data and utility values from KEYNOTE-024.

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Background/aim: Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose.

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Purpose: Treatment with regorafenib, which inhibits vascular endothelial growth factor (VEGF) receptor, frequently results in hand-foot skin reaction (HFSR), requiring treatment discontinuation or dose reduction. In our prospective study of regorafenib on patients with metastatic colorectal cancer, 17% of patients developed grade 3 HFSR. Herein, we retrospectively examined genetic polymorphisms associated with regorafenib-induced severe HFSR.

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Purpose: Capecitabine is a prodrug that converts to 5-fluorouracil (5-FU) in three steps. A previous study showed that ABCA2 rs2271862 (C > T) and ABCG5 rs6720173 were associated with increased clearance of 5-FU and 5'-deoxy-5-fluorouridine, respectively, in Spanish patients with colorectal cancer (CRC) (Br J Clin Pharmacol 2021) and reported that ABCA2 rs2271862 was associated with decreased risk of capecitabine-induced neutropenia. Other studies have reported that ABCB1 rs1128503, rs2032592, and rs1045642 were associated with capecitabine-induced toxicity in Spanish CRC patients (Oncotarget 2015, Phamacogenomics 2010).

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Regorafenib improves the survival of patients with metastatic colorectal cancer (mCRC); however, it is also characterized by detrimental dermal side effects that may require treatment cessation or modified dosing. In our previous prospective pharmacokinetic, pharmacodynamic, and pharmacogenetic studies, 17.5% (7/40) of the patients with mCRC had grade 3 erythema multiforme (EM) that caused treatment discontinuation.

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Background: The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported.

Objectives: We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy.

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Background: Gefitinib is recommended as a first-line treatment option for elderly patients with non-small cell lung cancer (NSCLC). Because no pharmacokinetics of gefitinib have been examined, we prospectively assessed the pharmacokinetics of gefitinib in patients with epidermal growth factor receptor gene-mutated advanced NSCLC who were 75 years or older.

Methods: Gefitinib was orally administered once daily at a dose of 250 mg.

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Article Synopsis
  • The study investigates the effectiveness and safety of durvalumab following chemoradiotherapy (CRT) using cisplatin and S-1 in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), a combination not previously evaluated prospectively.
  • Out of 59 patients treated, 86.4% successfully transitioned to durvalumab, with the most common reasons for not proceeding being disease progression and adverse events, though most issues were manageable.
  • The results show promising outcomes with a 62.7% objective response rate and high disease control rate, alongside low incidences of severe side effects like pneumonitis.
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Background: To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC.

Methods: Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients.

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Osimertinib is active against T790M-positive epidermal growth factor receptor mutant non-small cell lung cancer. We enrolled 122 sensitive epidermal growth factor receptor mutant non-small cell lung cancer patients who were planned to receive or were receiving first-/second-generation epidermal growth factor receptor tyrosine kinase inhibitors without disease progression and monitored plasma T790M every 1-2 months using the cobas® EGFR Mutation Test v2. We previously reported the concordance between T790M status in plasma and tissue.

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Rationale: Bladder cancer is one of the most common cancers worldwide. The anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab, which is an immune checkpoint inhibitor (ICI), has improved survival in bladder cancer. We report a case of bladder cancer that had a high antitumor effect with anti-programmed cell death PD-1 antibody pembrolizumab, an ICI, but asthma occurred an immune-related adverse event (irAE).

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Single nucleotide polymorphisms in genes encoding microRNAs (miRNA-SNPs) may affect the maturation steps of miRNAs or target mRNA recognition, leading to changes in the expression of target mRNAs to cause gain- or loss-of-function changes. Several miRNA-SNPs are known to be associated with the risk of diseases such as cancer. The purpose of this study was to comprehensively determine the miRNA-SNPs in Japanese individuals to evaluate the differences in allele frequencies between ethnicities by comparing data from the global population in the 1000 Genomes Project and differences between healthy subjects and cancer patients.

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Purpose: SN-38, a pharmacologically active metabolite of irinotecan, is taken up into hepatocytes by organic anion transporting polypeptide (OATP) 1B1. The effects of functional OATP1B1 521T>C on the pharmacokinetics of SN-38 remain controversial. Here, we prospectively examined the effects of OATP1B1 function on the area under the plasma total or unbound concentration-time curve (tAUC or uAUC) of SN-38 by assessing OATP1B1 521T>C and the plasma levels of endogenous OATP1B1 substrates, coproporphyrin (CP)-I and III, in cancer patients treated with irinotecan.

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Introduction: Immune checkpoint inhibitors (ICIs), particularly anti-PD-1 antibody, have dramatically changed cancer treatment; however, fatal immune-related adverse events (irAEs) can develop. Here, we describe a severe case of sclerosing cholangitis-like irAE. We report the use of 3 immunosuppressive agents that resulted in the death of the patient due to treatment inefficacy.

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Background/aim: Rapid tumor growth after administration of immune checkpoint inhibitors is designated hyper progressive disease (HPD). In this study, besides the conventional HPD category, we proposed the "super HPD" category where the disease is naturally rapidly growing.

Patients And Methods: Patients treated for advanced gastric cancer with irinotecan or nivolumab as a third-line treatment were retrospectively compared.

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Background: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings.

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Introduction: Dexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although our multicentre randomised double-blind comparative study verified non-inferiority of sparing DEX after day 2 of chemotherapy when combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) for patients receiving HEC regimen, DEX sparing was not non-inferior in patients receiving cisplatin (CDDP)-based HEC regimens in subgroup analysis. Recently, the efficacy of the addition of olanzapine (OLZ) to standard triple antiemetic therapy on HEC has been demonstrated by several phase III trials.

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Recently, cancer-related venous thromboembolism (VTE) has been termed "cancer-associated thrombosis (CAT)" and is the focus of current research. We retrospectively investigated the efficacy of a single-drug approach with edoxaban for the treatment of non-acute CAT. Thirty-two non-acute CAT patients who received edoxaban were analyzed.

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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.

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Paclitaxel has been considered to cause OATP1B-mediated drug-drug interactions at therapeutic doses; however, its clinical relevance has not been demonstrated. This study aimed to elucidate in vivo inhibition potency of paclitaxel against OATP1B1 and OATP1B3 using endogenous OATP1B biomarkers. Paclitaxel is an inhibitor of OATP1B1 and OATP1B3, with K of 0.

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Article Synopsis
  • - Regorafenib helps improve survival in patients with metastatic colorectal cancer but can cause serious side effects that might necessitate changes in dosage or treatment schedules.
  • - The drug is processed in the liver, leading to active metabolites M-2 and M-5, which have a much lower protein binding compared to regorafenib itself.
  • - Higher plasma concentrations of M-2 and M-5 correlated with shorter progression-free survival, suggesting that side effects, particularly during the first treatment cycle, can lead to discontinuation of the drug.
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Pancreatic cancer has an extremely poor prognosis, and identification of novel predictors of therapeutic efficacy and prognosis is urgently needed. Chemoresistance-related molecules are correlated with poor prognosis and may be effective targets for cancer treatment. Here, we aimed to identify novel molecules correlated with chemoresistance and poor prognosis in pancreatic cancer.

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Article Synopsis
  • The study investigated how VEGF inhibitors impact D-dimer levels in colorectal cancer patients, particularly regarding venous thromboembolism (VTE) diagnosis.
  • 104 colorectal cancer patients undergoing chemotherapy were analyzed, split into groups with and without VTE.
  • Results showed that VEGF inhibitors do not significantly raise D-dimer levels in patients without VTE, suggesting they don't interfere with VTE diagnosis.
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Rationale: We developed a new high-throughput method to analyze tegafur (FT) and 5-fluorouracil (5-FU) in tear and plasma samples using hydrophilic interaction liquid chromatography (HILIC)/tandem mass spectrometry (MS/MS).

Methods: The tear samples (10 μL) spiked with FT, 5-FU, and 5-chlorouracil (internal standard) were diluted using 40 μL of 2 M ammonium acetate and 250 μL of acetonitrile with 2% formic acid; 20 μL of plasma spiked with the two drugs and internal standard was diluted with 80 μL of 2 M ammonium acetate and 500 μL of acetonitrile with 2% formic acid. After centrifugation, the clear supernatant extract (15 μL) was directly injected into the HILIC/MS/MS instrument, and each drug was separated on a Unison UK-Amino column (50 mm × 3 mm i.

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Purpose: Several retrospective studies have shown that the antitumor efficacy of capecitabine-containing chemotherapy decreases when co-administered with a proton pump inhibitor (PPI). Although a reduction in capecitabine absorption by PPIs was proposed as the underlying mechanism, the effects of PPIs on capecitabine pharmacokinetics remain unclear. We prospectively examined the effects of rabeprazole on the pharmacokinetics of capecitabine and its metabolites.

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