Kanako Azuma

Bio: Kanako Azuma is an academic researcher from Tokyo Medical University. The author has contributed to research in topics: Medicine & Criterion validity. The author has an hindex of 6, co-authored 10 publications receiving 325 citations.

The Japanese version of the National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE): psychometric validation and discordance between clinician and patient assessments of adverse events

Abstract: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed by the National Cancer Institute as an adverse event assessment system to evaluate patients’ symptoms, which tend to be underestimated in cancer clinical trials. The aim of this study was to assess the psychometric properties of the Japanese version of the PRO-CTCAE and the degree of adverse event assessment discordance between clinicians and patients. A total of 187 cancer patients receiving systemic therapy were enrolled. Reproducibility, criterion validity, and responsiveness of the Japanese version of PROCTCAE were assessed. The EORTC QLQ-C30 was used as an external anchor. Discordance of assessment of adverse events between clinician and patients were also assessed using the CTCAE and PRO-CTCAE. A total of 187 participants (187 for criterion validity, 80 for reproducibility, and 100 for responsiveness), were analyzed (Mage = 62.4 years). All patients responded to at least one symptom item (M = 16). The mean (SD) intra-class correlation coefficients of overall reproducibility for the Japanese PRO-CTCAE was 0.63 (0.02). The correlation coefficient for the corresponding items in the EORTC QLQ-C30 and the Japanese PRO-CTCAE was high (Pearson r = 0.56–0.76). The analysis of responsiveness revealed significant dose-response trends (Jonckheere-Terpstra test, ps < 0.001). Depending on the adverse events, a discrepancy was observed in evaluation between the clinician and patient. These results revealed that there is underestimation in the assessment of adverse events in Japan, and that the Japanese version of the PRO-CTCAE had acceptable reliability and validity for common and clinically important symptoms.

Development and validation of the Japanese version of the Decisional Conflict Scale to investigate the value of pharmacists’ information: a before and after study

Abstract: The information provided in patient-centered care and shared decision-making influences patients’ concerns and adherence to treatment. In the decision-making process, patients experience decisional conflict. The Decisional Conflict Scale (DCS) is a 16-item, self-administered questionnaire consisting of 5 subscales developed to assess patients’ decisional conflict. This study aimed to develop the Japanese version of the DCS and to clarify the influence of the information provided by pharmacists’ on decisional conflict among patients with cancer. We developed the Japanese version of the DCS by using the forward-backward translation method. One hundred patients who were recommended a new chemotherapy regimen were recruited. The psychometric properties of the Japanese DCS, including internal consistency, convergent validity, discriminant validity, and construct validity, were examined. We assessed the decisional conflict of patients before and after the pharmacists’ provision of information. Ninety-four patients, predominately female, with an average age of 58.1 years were sampled. The scores on the 5 subscales of the DCS showed high internal consistency (Cronbach’s alpha = 0.84–0.96). Multi-trait scaling analysis and cluster analysis showed strong validity. The mean total DCS score decreased significantly from 40.2 to 31.7 after patients received information from the pharmacists (p < 0.001, paired t-test). Scores on all 5 subscales, namely, uncertainty, informed, values clarity, support, and effective decision, also significantly improved (p < 0.001 for all categories, paired t-test). The psychometric properties of the Japanese version of the DCS are considered appropriate for it to be administered to patients with cancer. Pharmacists’ provision of information was able to decrease decisional conflict among patients with cancer who were recommended a new chemotherapy regimen.

Assessment of Cancer-Related Fatigue, Pain, and Quality of Life in Cancer Patients at Palliative Care Team Referral: A Multicenter Observational Study (JORTC PAL-09)

Abstract: Introduction Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams.

Patient-generated health data collection using a wearable activity tracker in cancer patients—a feasibility study

Abstract: Incorporation of patient-generated health data (PGHD) into clinical research requires an investigation of the validity of outcomes and feasibility of implementation. This single-arm pilot trial investigated the feasibility of using a commercially available activity tracking wearable device in cancer patients to assess adherence to the device and real-time PGHD collection in a clinical research setting. From July to November 2017, enrolled adult patients were asked to wear a wristband-style device. Brief Fatigue Inventory (BFI) and MD Anderson Symptom Inventory (MDASI) were assessed at baseline and on day 29. Furthermore, 29-day Pittsburgh Sleep Quality Index, global impression of the devices, and NCI CTCAE v4 were evaluated. Of 30 patients (mean age, 58.6 years; male, 21 [70%]), 15 (50%) and 11 (36.7%) had gastrointestinal and lung cancer, respectively, and 27 (90%, 95% CI: 0.74–0.98) were well adhered (> 70%) to the device for 28 days. The mean adherence was 84.9% (range: 41.7–95.2%). More frequent PGHD synchronization tended to show better device adherence, with moderate correlation (r = 0.62, 95% CI: 0.33–0.80, p < 000.1). The feasibility of using a wearable activity tracker was confirmed in cancer patients receiving chemotherapy for a month. For future implementation in clinical trials, there is a need for further comprehensive assessment of the validity and reliability of wearable activity trackers. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN: UMIN000027575.

Palonosetron (PALO) versus granisetron (GRA) in the triplet regimen with dexamethasone (DEX) and aprepitant (APR) for preventing chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC) with cisplatin (CDDP): A randomized, double-blind, phase III trial.

Abstract: 9621 Background: Standard antiemetic care for preventing CINV due to HEC is a combination of 5-HT3 receptor antagonist (RA), DEX, and APR. This study compared the efficacy of two 5-HT3drugs, PALO and GRA, in the triplet regimen. Methods: Pts with a malignant solid tumor who were receiving HEC containing 50 mg/m2or more CDDP were enrolled. They were randomly assigned to either Arm A (PALO 0.75 mg, i.v.) or Arm B (GRA 1 mg, i.v.), 30 min before chemotherapy on day 1, both arms with DEX (9.9 mg on day 1 and 6.6 mg on day 2-4, i.v.) and APR (125 mg on day 1 and 80 mg on day 2–3, p.o.). Primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medications) at the overall (0-120 hours) phase. Secondary endpoints included CR at the acute (0-24 h) and delayed (24-120 h) phases, and total control (TC; no emetic episodes, no rescue medications, and no nausea) at the overall, acute, and delayed phases. The planned sample size of 840 provided 90% power to detect a 10% improvement in the ...

The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics

Abstract: In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept. Gut microbiota can be manipulated to benefit host health, including the use of probiotics, prebiotics and synbiotics. This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019.

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers.

Abstract: PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86–100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8–55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8+PD-1+ T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data. Results from the NICHE study show remarkable pathological responses to neoadjuvant combination immunotherapy in patients with early-stage colon cancer and uncover potential biomarkers of response.

Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

Abstract: Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts. Treatment commenced with a 3-week dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety expansion. Results NHL subtypes included mantle cell lymphoma (MCL; n = 28), follicular lymphoma (FL; n = 29), diffuse large B-cell lymphoma (DLBCL; n = 34), DLBCL arising from chronic lymphocytic leukemia (Richter transformation; n = 7), Waldenstrom macroglobulinemia (n = 4), and marginal zone lymphoma (n = 3). Venetoclax was generally well tolerated. Clinical tumor lysis syndrome was not observed, whereas laboratory tumor lysis syndrome was documented in three patients. Treatment-emergent adverse events were reported in 103 patients (97%), a majority of which were grade 1 to 2 in severity. Grade 3 to 4 events were reported in 59 patients (56%), and the most common were hematologic, including anemia (15%), neutropenia (11%), and thrombocytopenia (9%). Overall response rate was 44% (MCL, 75%; FL, 38%; DLBCL, 18%). Estimated median progression-free survival was 6 months (MCL, 14 months; FL, 11 months; DLBCL, 1 month). Conclusion Selective targeting of BCL-2 with venetoclax was well tolerated, and single-agent activity varied among NHL subtypes. We determined 1,200 mg to be the recommended single-agent dose for future studies in FL and DLBCL, with 800 mg being sufficient to consistently achieve durable response in MCL. Additional investigations including combination therapy to augment response rates and durability are ongoing.

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial

Abstract: Summary Background Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer. Methods The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0–2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin–etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up. Findings Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35–58), median overall survival was 30 months (95% CI 24–34) in the twice-daily group versus 25 months (21–31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95–1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50–62) in the twice-daily group and 51% (45–57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI −3·2% to 13·7%]). The most common grade 3–4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3–4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3–4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group). Interpretation Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting. Funding Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups).

Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA.

Abstract: Purpose Cabazitaxel 25 mg/m2 (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m2 (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25. To claim noninferiority of C20 (maintenance of ≥ 50% of the OS benefit of C25 v mitoxantrone in TROPIC) with 95% confidence level, the upper boundary of the CI of the hazard ratio (HR) for C20 versus C25 could not exceed 1.214 under a one-sided 98.89% CI after interim analyses. Secondary end points included progression-free survival, prostate-specific antigen (PSA), tumor and pain responses and progression, health-related quality of life, and safety. Results Overall, 1,200 patients were randomly assigned (C20, n = 598; C25, n = 602). Baseline characteristics were similar in both arms. Median OS was 13.4 months for C20 and 14.5 months for C25 (HR, 1.024). The upper boundary of the HR CI was 1.184 (less than the 1.214 noninferiority margin). Significant differences were observed in favor of C25 for PSA response (C20, 29.5%; C25, 42.9%; nominal P < .001) and time to PSA progression (median: C20, 5.7 months; C25, 6.8 months; HR for C20 v C25, 1.195; 95% CI, 1.025 to 1.393). Health-related quality of life did not differ between cohorts. Rates of grade 3 or 4 treatment-emergent adverse events were 39.7% for C20 and 54.5% for C25. Conclusion The efficacy of cabazitaxel in postdocetaxel patients with mCRPC was confirmed. The noninferiority end point was met; C20 maintained ≥ 50% of the OS benefit of C25 versus mitoxantrone in TROPIC. Secondary efficacy end points favored C25. Fewer adverse events were observed with C20.