Hiroi Kasai - Academia.edu (original) (raw)

Papers by Hiroi Kasai

Breast Cancer Research and Treatment, 2021

Purpose To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-n... more Purpose To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Methods Patients in group A (aged < 65 years with homologous recombination deficiency, HRD, score ≥ 42, or those at any age with germline BRCA mutation, gBRCAm) were randomized to 4 cycles of paclitaxel plus carboplatin (group A1) or eribulin plus carboplatin (group A2), followed by 4 cycles of anthracycline. Patients in group B (aged < 65 years with HRD score < 42, or aged ≥ 65 years without gBRCAm) were randomized to 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2); non-responders to the first 4 cycles of the eribulin-based therapy received anthracycline. Primary endpoint was pCR rate (ypT0-is, ypN0; centrally confirmed). Main secondary endpoint was safety. Results The full analysis set comprised 99 patients. The pCR rate was 65% (90% CI, 46%–81%) and 45% (27%–65%) in groups A1 and A2, respect...

Frontiers in Bioengineering and Biotechnology, 2020

Medical products comprising human cells, genes, and tissues have been developed for clinical appl... more Medical products comprising human cells, genes, and tissues have been developed for clinical applications worldwide, and their developmental environment has been established. These products can be imported and exported, but marketing authorization regulations are complicated among regions. This investigation was conducted to identify the characteristics of medical products comprising human cells, genes, and tissues. We used website data, books from survey companies, and reports from public agencies to conduct two investigations. We used website data to conduct a general information survey of 143 cell-therapy and gene-therapy products sold in 24 countries and public assessment reports to individually survey non-clinical and clinical developments of 18 cell-therapy and gene-therapy products developed in Japan and the European Union (EU). The first survey revealed that the numbers of products used in orthopedic surgery and dermatology have increased since 2000, and the numbers of hemat...

Journal of medical and dental sciences, 2006

Along with continued efforts to improve data quality in clinical trials, it is imperative to make... more Along with continued efforts to improve data quality in clinical trials, it is imperative to make critical assessments about the recognition, traceability, and validation of the data on final outputs of clinical trials. The present study investigated protocols in 36 clinical trials and case report forms (CRFs) for 141 patients. CRFs were categorized as Book Type (BT), Visit Type (VT), and Separate binding Type (ST). The achievement of recognition, traceability, and validation of the data in CRFs was assessed using arbitrary grading scales. There were significant differences between the VT and BT conditions in terms of traceability and validation 1 (the integrity of clinical laboratory test data). No significant differences were observed among the three types of CRFs in terms of recognition and validation 2 (verification of test drug compliance). These findings indicate that the traceability and the integrity of clinical laboratory test data depend on the structure of the CRFs used, ...

163MO Randomized phase II study of eribulin-based neoadjuvant chemotherapy for triple-negative primary breast cancer patients stratified by homologous recombination deficiency status (JBCRG-22)

Annals of Oncology, 2020

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics, 2020

Background : Limited data are available to create an effective instruction strategy for clinical ... more Background : Limited data are available to create an effective instruction strategy for clinical research coordinators (CRCs)based on their experience(years). We aimed to understand the association between the expertise level and experience of CRCs. Methods : Data from a survey that developed a scale for evaluating the expertise level of CRCs were used. Pearsonʼs coefficients of correlation were calculated to examine the association among the following four subscales : knowledge, basic skills, management skills and attitude, and experience(years). The mean scores on the subscales were compared among 5 groups categorized as per experience(years)using analysis of variance and multiple comparisons. Results : Total 974 valid responses were received. Pearsonʼs coefficient of correlation among the three subscales of knowledge, basic skill and management skill, and experience(years)wasB0.5. The mean score of CRCs withB11 years of experience was 3.9／5 for knowledge, 4.5／5 for basic skills, 4.0／5 for management skills, and 4.0／5 for attitude. The mean scores for each subscale were significantly different for all five groups. However, there were no significant differences among several groups in multiple comparisons. Conclusion : Knowledge, basic skills, and management skills of CRCs are associated with their professional experience (years). However, the basic skills do not improve after six years of experience ; knowledge and management skills do not match those of an expert. Attitude is not associated with experience.

Breast Cancer, 2018

Background Dual blockade of HER2 promises increased pathological complete response (pCR) rate com... more Background Dual blockade of HER2 promises increased pathological complete response (pCR) rate compared with single blockade in the presence of chemotherapy for HER2-positive (+) primary breast cancer. Many questions remain regarding optimal duration of treatment and combination impact of endocrine therapy for luminal HER2 disease. Methods We designed a randomised phase II, five-arm study to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks) followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks) with/without prolongation of anti-HER2 therapy prior to chemotherapy (18 vs. 6 weeks), and with/without endocrine therapy in patients with HER2+ and/or oestrogen receptor (ER)+ disease. The primary endpoint was comprehensive pCR (CpCR) rate. Among the secondary endpoints, pCR (yT0-isyN0) rate, safety, and clinical response were evaluated. Results In total, 215 patients were enrolled; 212 were included in the full analysis set (median age 53.0 years; tumour size = T2, 65%; and tumour spread = N0, 55%). CpCR was achieved in 101 (47.9%) patients and was significantly higher in ER− patients than in ER+ patients (ER− 63.0%, ER+ 36.1%; P = 0.0034). pCR with pN0 was achieved in 42.2% of patients (ER− 57.6%, ER+ 30.3%). No significant difference was observed in pCR rate between prolonged exposure groups and standard groups. Better clinical response outcomes were obtained in the prolongation phase of the anti-HER2 therapy. No surplus was detected in pCR rate by adding endocrine treatment. No major safety concern was recognised by prolonging the anti-HER2 treatment or adding endocrine therapy. Conclusions This study confirmed the therapeutic impact of lapatinib, trastuzumab, and paclitaxel therapy for each ER− and ER+ subgroup of HER2+ patients. Development of further strategies and tools is required, particularly for luminal HER2 disease.

European Journal of Cancer, 2015

annual frequency of 0.3. The use of chest radiographs, abdominal and pelvic ultrasounds, and tumo... more annual frequency of 0.3. The use of chest radiographs, abdominal and pelvic ultrasounds, and tumor markers (CEA, CA 15−3) were regularly performed although it is not recommended for routine follow-up according to the guidelines. The complete blood counts and chemistry panels were done according to the national guidelines although this is not recommended by international guidelines. Conclusion: Among postmenopausal women with early, hormone receptor-positive breast cancer receiving adjuvant endocrine therapy in Croatia, more follow-up procedures were done compared to the guidelines' recommendations. Use of diagnostic tests not proven to increase overall, recurrence free-or disease-specific survival during standard follow-up in early breast cancer patients is not cost-effective and has become large, unnecessary burden for overstretched and limited transition countries' budgets.

P203 Dual HER2 blockage with lapatinib and trastuzumab for Japanese patients with HER2+ breast cancer

The Breast, 2015

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics, 2016

Introduction : The recent revision of the Declaration of Helsinki strengthened the ethical obliga... more Introduction : The recent revision of the Declaration of Helsinki strengthened the ethical obligation to provide compensation for harm of research subjects. However, the actual status of providing compensation has rarely been disclosed, especially in the situation of investigator-initiated clinical trials(IITs). Objectives : To figure out the actual situation of compensation for injured subjects of IITs in Japan and to identify the necessary steps to fulfill the ethical obligation of compensation. Method : We conducted two types of surveys of compensation in IITs in Japan over the past five years. A : questionnaire survey delivered to 1,700 institutions on(1)number and paid amount of compensation cases ; number and amount of contract fees paid to insurance companies ; and (2) institutional management system of compensation cases. B : complementary survey to the item(1) of the survey A, at two institutions, on contract fees paid to and insurance paid from insurance companies. Result : In the survey A, we found only two cases of compensation provided, but could not find any serious cases claiming payment from insurance companies, although we could not exclude possibility of undisclosed cases. In the survey B, at the two institutions, a substantial amount of contract fees has been paid to insurance companies without claiming insurance payment ; however, the total amount for each institution is less than that expected for one case of a serious injury. Also we found that there remain several points to improve the institutional management system of compensation in IITs in Japan. Conclusion : To provide appropriate compensation for injured subjects of IITs, we need to develop an institutional management system, along with a system to gather statistical information of compensation cases, to achieve proper resource allocation. This system should also provide education for investigators and support staff to manage injury cases.

Journal of Cardiovascular Electrophysiology, 1998

Supernormal Intraventricular Conduction. Introduction: Conduction time (CT) is given by the formu... more Supernormal Intraventricular Conduction. Introduction: Conduction time (CT) is given by the formula: conducting distance divided by conduction velocity. Based on this formula, we hypothesized that CT shortening (i.e., supernormal conduction) may result from dimensional shortening of the distance of impulse propagation, which naturally occurs during ventricular systole. Methods and Results: To test the above, two separate groups of patients were studied, group A {14 patients) for electrophysiologic study and group B (12 patients) for echocardiographic study. In group A patients, CT from the stimulus artifact to the basal lateral wall of the left ventricle (LV) (S-LV interval) was measured using right ventricular (RV) apical extrastimulus testing. S-LV interval shortening in premature RV beats was demonstrated in all 14 patients. The maximum shortening was 20 ± 9 msec (range 10 to 40), and the maximum % shortening was 16% ± 6% (7% to 27%). In group B patients with implanted pacemakers, the major (long) and minor (short) axis dimensions of the LV were measured with echocardiography. The major axis dimension was used as an approximate measure of the linear length from the RV apex to the basal lateral wall of LV. The maximum % shortening of the major axis dimensions was 15% ± 4%, 16% ± 2%, and 11 % ± 4% during VVI pacing, respectively, at paced cycle lengths of 1,000 (11 patients), 800 (5 patients), and 600 msec (12 patients). The maximum % shortening of the S-LV intervals was comparahle in magnitude with that of the major axis dimensions: 20% versus 15% ± 4%, 15% ± 7% versus 16% ± 2% and 16% ± 6% versus 11% ± 4%, respectively, at paced cycle lengths of 1,000, 800, and 600 msec. There was also a good temporal correlation between the electrophysiologic (CT shortening) versus echocardiographic (dimensional shortening) parameters. Thus, the intraventricular CT and the major axis dimension of the LV were shortened in a similar magnitude and also at a similar timing in the cardiac cycle. Conclusion: These fmdings suggest the possibility that supernormal conduction may result, at least in part, from dimensional shortening of the pathway length of impulse propagation from the stimulating to recording electrodes, which naturally occurs during ventricular systole.

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics, 2009

Japanese Journal of Electrocardiology, 1998

Oncotarget, Jan 20, 2016

Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (C... more Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (CRT) for esophageal cancer. However, PDT required long sun shade period. This study aimed to evaluate the safety and efficacy of PDT using second generation photosensitizer, talaporfin sodium for local failure after CRT. This was the multi-institutional non-randomized phase II study. Patients with histologically proven local failure limited within the muscularis propria after 50Gy or more radiotherapy (RT) for esophageal cancer were eligible. We set the primary endpoint as local complete response (L-CR) per patients. And, secondary endpoints were confirmed L-CR, local progression free survival (L-PFS), progression free survival (PFS), overall survival (OS), L-CR per lesions (Lesion L-CR), and confirmed Lesion L-CR. The PDT procedure commenced with intravenous administration of a 40 mg/m2 dose of talaporfin sodium followed by diode laser irradiation at a 664 nm wavelength. 26 eligible pati...

PloS one, 2014

Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotro... more Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. T...

$Research paper thumbnail of Multicenter phase II study of trifluridine/tipiracil for esophageal squamous carcinoma refractory/intolerant to 5-fluorouracil, platinum compounds, and taxanes: the ECTAS study$

Multicenter phase II study of trifluridine/tipiracil for esophageal squamous carcinoma refractory/intolerant to 5-fluorouracil, platinum compounds, and taxanes: the ECTAS study

Esophagus

Therapeutic Innovation & Regulatory Science

Background The International Council for Harmonisation of Technical Requirements for Pharmaceutic... more Background The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders. Methods A total of 105 academic stakeholders from 18 institutions responded to the survey. The research group developed recommendations reflecting the survey results and the opinions from patients and the public. Results The survey showed the top four principles needing renovation were (i) informed consent (Chapter 2.9, 12.4% of respondents believed it needed renovation), (ii) systems for quality assurance (Chapter 2.13, 9.5%), (iii) information on an investigational product (Chapter 2.4, 5.7%), and (iv) proce...

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics

Background : There is a lack of information to create an effective instruction strategy for clini... more Background : There is a lack of information to create an effective instruction strategy for clinical research coordinators(CRCs). This study aimed to develop a scale that evaluates the level of expertise of CRCs. Methods : The original scale was developed including 96 items based on items reviewed by several researchers and the results of a pilot survey. The original scale was distributed to 12 CRCs who attended a training program at an academic society to investigate its test-retest reliability. The original scale was also distributed to another group of CRCs at medical institutes or site management organizations in order to perform exploratory factor analysis and confirmatory factor analysis. Results : The interclass correlation coefficient of the whole scale was 0.957 through the first survey of 12 CRCs. Exploratory factor analysis by the maximum-likelihood approach with promax rotation indicated 4 factors, i.e., knowledge, attitude, management skill and basic, from 90 items. Cronbachʼs a of the whole scale was 0.984, and those of the subscales were 0.943-0.979. Regarding fit indexes, chi-square value was 35732.138(p＜0.01), Goodness of Fit Index (GFI) was 0.449, Adjusted GFI (AGFI) was 0.423, and Root Mean Square Error of Approximation(RMSEA) was 0.091 from the results of confirmatory factor analysis. Conclusion : The scale that evaluates the level of expertise of CRCs that we developed is reliable and valid although there was an issue regarding fitness of the model.

A descriptive research: Exclusion from submitted clinical data package in the review process of new drug approval due to GCP violation in Japan

Contemporary Clinical Trials Communications

$Research paper thumbnail of O3-7-6ECTAS: A phase II study of TAS-102 for advanced/recurrent esophageal cancer refractory/intolerable to standard therapies$

O3-7-6ECTAS: A phase II study of TAS-102 for advanced/recurrent esophageal cancer refractory/intolerable to standard therapies