Biomedical subjects

Hirofumi Mukai

Publications and source records attributed to Hirofumi Mukai.

9 recordsLinked to original sources

PubMed2026

Pembrolizumab plus chemotherapy followed by pembrolizumab in participants in Asia with early triple-negative breast cancer: An updated subgroup analysis of the KEYNOTE-522 randomized clinical trial.

BACKGROUND: In KEYNOTE-522 (NCT03036488), addition of perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR), event-free survival (EFS), and overall survival (OS) in early-stage triple-negative breast cancer (TNBC). pCR and EFS results in participants enrolled in Asia were consistent with those in the overall population. We report OS, updated EFS, and safety outcomes in participants enrolled in Asia. METHODS: Participants with newly diagnosed, high-risk, early-stage TNBC (T1c [N1‒N2] or T2‒T4 [N0‒N2] per AJCC 7th edition) were randomized 2:1 to 8 cycles of neoadjuvant pembrolizumab 200 mg Q3W or placebo plus chemotherapy. After definitive surgery, participants received adjuvant pembrolizumab 200 mg Q3W or placebo for ≤9 cycles. Primary endpoints were pCR (ypT0/Tis ypN0) and EFS. OS was a secondary endpoint. RESULTS: Of 1174 randomized participants, 216 were enrolled in Asia. At data cutoff (March 22, 2024), EFS events occurred in 18/136 participants (13.2%) in the pembrolizumab + chemotherapy group versus 22/80 (27.5%) in the placebo + chemotherapy group (HR, 0.43 [95% CI, 0.23‒0.81]); 60-month EFS rates (95% CIs) were 87.4% (80.6%‒92.0%) and 72.1% (60.7%‒80.6%), respectively. In the respective groups, 12/136 (8.8%) and 16/80 participants (20.0%) died (HR, 0.41 [95% CI, 0.19‒0.86]); 60-month OS rates (95% CIs) were 91.9% (85.8%‒95.4%) and 81.1% (70.5%‒88.1%). Treatment-related AEs led to treatment discontinuation in 19/136 participants (14.0%) with pembrolizumab + chemotherapy and 7/79 (8.9%) with placebo + chemotherapy. CONCLUSIONS: OS and updated EFS outcomes in KEYNOTE-522 participants enrolled in Asia were consistent with those in the overall population and support use of perioperative pembrolizumab + neoadjuvant chemotherapy as a standard-of-care treatment in this setting.

Adjuvant↗

PubMed2026

Quality of life with palbociclib plus tamoxifen in hormone receptor-positive, HER2-negative advanced breast cancer: results from PATHWAY, an Asian international, double-blind, randomized phase 3 trial.

BACKGROUND: In the Asian international PATHWAY trial, palbociclib-tamoxifen demonstrated improved progression-free survival compared with placebo-tamoxifen in patients with HR+/HER2- locally advanced or metastatic breast cancer (ABC). This analysis compared quality of life (QoL) between treatment arms. METHODS: Pre/peri or postmenopausal women with HR+/HER2- ABC were randomly assigned 1:1 to receive palbociclib-tamoxifen or placebo-tamoxifen. Patient-reported outcomes were assessed on day 1 of cycles 1 (baseline), 4, and 7, and at the end of treatment (EOT) using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Least-square mean (LSM) changes in scores from baseline were calculated. Kaplan-Meier method was used to calculate time to deterioration (TTD) in the minimally important difference (MID) in the pain subscale. RESULTS: In the comparison between treatment arms, no significant differences were observed in LSM changes in scores from baseline in global QoL (cycle 4: 0.70 [95% confidence interval (CI): -5.00, 6.41]; cycle 7: 2.17 [95% CI: -4.14, 8.48]; EOT: -5.19 [95% CI: -11.64, 1.26]). For both the EORTC QLQ-C30 and QLQ-BR23 functional and symptom subscales, no clinically meaningful differences between treatment arms were found in the LSM changes in scores from baseline. Median TTD in the MID in the pain subscale was 32.5 months (95% CI: 11.7, not estimable) for the palbociclib-tamoxifen arm and 21.2 months (95% CI: 5.5, 43.5) for the placebo-tamoxifen arm (hazard ratio = 0.729 [95% CI: 0.467, 1.138]). CONCLUSIONS: The combination of palbociclib and tamoxifen delayed deterioration in patients' QoL while they experienced reduced risk for disease progression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03423199; study registration date: February 6, 2018.

Humans↗

PubMed2006

An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients.

We report three cases of patients with advanced cancer who showed severe hepatic damage, and two of whom died of fulminant hepatitis. All the patients were taking Agaricus blazei (Himematsutake) extract, one of the most popular complementary and alternative medicines among Japanese cancer patients. In one patient, liver functions recovered gradually after she stopped taking the Agaricus blazei, but she restarted taking it, which resulted in deterioration of the liver function again. The other patients who were admitted for severe liver damage had started taking the Agaricus blazei several days before admission. Although several other factors cannot be completely ruled out as the causes of liver damage, a strong causal relationship between the Agaricus blazei extract and liver damage was suggested and, at least, taking the Agaricus blazei extract made the clinical decision-making process much more complicated. Doctors who are aware of their patients taking the extract may accept it probably because they believe there is no harm in a complementary and alternative medicine. When unexpected liver damage is documented, however, doctors should consider the use of the Agaricus blazei extract as one of its causal factors. It is necessary to evaluate many modes of complementary and alternative medicines, including the Agaricus blazei extract, in rigorous, scientifically designed and peer-reviewed clinical trials.

Agaricus↗

PubMed2006

Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors.

BACKGROUND: To evaluate the role of FDG-PET in assessing anti-tumor efficacy of molecular targeted drugs, we prospectively performed FDG-PET and CT for response evaluation in patients treated with lapatinib, a dual inhibitor of ErbB1 and ErbB2 tyrosine kinases. METHODS: Lapatinib was given orally once a day at doses ranging from 1200 to 1800 mg in a phase I study. CT and FDG-PET were performed before treatment, and at 1, 2 and 3 months after the initiation of the treatment and every 2 months thereafter. RESULTS: A total of 29 FDG-PET examinations were performed in eight patients with various solid tumors and the metabolic activity in the tumor was evaluated as SUVmax. The best responses, as assessed by CT, were as follows; one partial response, four stable disease and three disease progression. The partial response was observed in a patient with trastuzumab-resistant breast cancer, whose SUVmax was decreased by 60% from baseline. In all of the four patients whose best response was stable disease, the SUVmax was decreased by 6-42% one month after the start of treatment. Prolonged stable disease (10 months) was observed in a patient with colon cancer, whose SUVmax was decreased by 42%. In the patient group with disease progression, SUVmax was increased in two out of three patients. CONCLUSIONS: FDG-PET detected decreases in the metabolic activity of the tumors in patients who experienced clinical benefits on treatment with lapatinib. Thus, FDG-PET may be useful for the evaluation of molecular targeted drugs, such as lapatinib.

Adult↗

PubMed2006

The outpatient management of low-risk febrile patients with neutropenia: risk assessment over the telephone.

OBJECTIVE: The purpose of this retrospective study is to evaluate the feasibility of the risk assessment over the telephone in the outpatient management of low-risk febrile patients with neutropenia. MATERIALS AND METHODS: Febrile patients with neutropenia were eligible for outpatient management with oral ciprofloxacin if they demonstrated the following characteristics: resolution of neutropenia expected in <10 days, good performance status, controlled cancer, no symptoms or signs suggesting systemic infection other than fever, and no comorbidity requiring hospitalization. Eligible patients received oral ciprofloxacin (400 mg, three times daily) and were monitored as far as possible by telephone. Risk assessment concerning general condition was carried out over the telephone. RESULTS: Of the 60 consecutive patients who received neoadjuvant chemotherapy as a phase II trial of docetaxel (60 mg/m(2)) and doxorubicin (50 mg/m(2)) for primary breast cancer, 30 low-risk febrile patients received oral ciprofloxacin. Twenty-seven of these patients (90%) recovered uneventfully without hospitalization and the use of granulocyte colony-stimulating factor. Treatment was considered to have failed in the remaining three (10%) on the account of the need to modify or change their regimens. CONCLUSIONS: For carefully selected low-risk febrile patients with neutropenia, risk assessment over the telephone may be convenient, and close daily medical scrutiny may be not routinely required in the outpatient.

Adult↗

PubMed2006

[Treatment guidelines for systemic adjuvant therapy of breast cancer].

The rapidly growing body of knowledge provided by an efficient clinical trials process requires periodic revisions of clinical practice guidelines. These guidelines are prepared by experts whose delicate task is to digest the evidence provided by the clinical trials which may indicate a weak or a strong average treatment effect for a patient population and to translate this evidence into implications for individual patient care. Guidelines are thought to enhance the quality of care by reducing under-treatment, over-treatment and wrong treatment. At least one study has shown an adverse impact on overall mortality if treatment guidelines are not followed. Guidelines that have authority in the adjuvant treatment of breast cancer are the NIH and NCCN guidelines, those developed in St. Gallen and those by Japan Breast Cancer Society.

Breast Neoplasms↗

PubMed2003

Unknown primary carcinoma: a feasibility assessment of combination chemotherapy with cisplatin and docetaxel.

BACKGROUND: Docetaxel (Taxotere) and cisplatin are two of the most active single agents used in the treatment of solid tumors. We examined the feasibility of using a combination of docetaxel and cisplatin for the treatment of unknown primary carcinoma in order to prepare a larger scale prospective study. METHODS: Eligible patients were aged 18 to 75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less and a life expectancy of 8 weeks or more, and had been diagnosed as having unknown primary carcinoma by the required examinations. Patients were not permitted to have received prior chemotherapy and had to have measurable lesions. Docetaxel (60 mg/m(2)) was given intravenously over a 1-h period immediately before cisplatin (80 mg/m(2)), which was given intravenously over a 2-h period, every 3 weeks. Premedication included dexamethasone, granisetron, and standard hyperhydration. RESULTS: Twenty-six treatment courses in five patients were tested according to the protocol and feasibility was assessed. Adverse events observed included grade 4 neutropenia, leukopenia, grade 3 nausea/vomiting, grade 2 diarrhea, and mucositis. These adverse events were well tolerated, reversible, and manageable. Doses were not reduced and all injections were given or their due date without any delay in all patients. Four patients achieved a partial response and one had stable disease. CONCLUSION: Treatment of patients with unknown primary carcinoma with a combination of docetaxel and cisplatin is feasible. Conduct of a phase II trial of this regimen is warranted.

Adolescent↗

PubMed2003

Standardization of the body surface area (BSA) formula to calculate the dose of anticancer agents in Japan.

BACKGROUND: The importance of deciding the appropriate dose of anticancer agents cannot be overemphasized. Body surface area (BSA) has been used to calculate the dose in anticancer therapy since the 1950s. Japanese oncologists, often use their own Japanese BSA formula instead of western BSA formulae. However, it is not widely known that some discrepancies exist between the BSA products of the Japanese and western styles. On the other hand, recently dose-calculations according to BSA were criticized from the standpoint of pharmacokinetics (PK). Lately, we have had many opportunities for international collaborations, which make it necessary to review these BSA formulae, and the BSA-based dosing method. A unified BSA formula in cancer therapy is needed in Japan. METHODS: We searched and compiled frequently used BSA formulae across the world using the MEDLINE search, oncology text, a web search on cancer clinical trial groups, and personally communicated with medical oncologists from western countries. Using these formulae, we calculated BSA for a typical Japanese individual, and compared their products. We calculated BSA using these formulae for individuals of widely varying physique, from 140 to 185 cm in height, and from 30 to 96 kg in weight, and estimated the amount of discrepancies among them. RESULTS: Among the various BSA formulae used in western countries, the DuBois formula is the standard. In Japan, the Fujimoto formula has been used frequently. The Fujimoto formula was based on a study of 201 Japanese subjects in 1949. For the average Japanese individual, the BSA calculated using the Fujimoto formula was about 3% lower than that which was calculated by western formulae. The BSA calculated for all heights and body weights using the Fujimoto formula, ranged between 0.7 and 4.8% less than those calculated by using the DuBois formula. The other western formulae showed larger discrepancies than the Fujimoto and DuBois formulae. CONCLUSION: BSA-based dosing has failed to standardize the variation in PK for most anticancer agents, and individual dosing techniques are currently being investigated. However, until their clinical utilities are confirmed, it is necessary to depend on the BSA-based calculation for determining the dose of most anticancer agents. The DuBois formula, which is the western standard formula, is validated to a greater extent and its accuracy has been confirmed more than others, including the Fujimoto formula. We recommend the use of the DuBois formula instead of the Fujimoto formula in cancer chemotherapy and propose the standardization of this formula in Japan.

Adult↗

PubMed2002

[Genetic testing for effective Herceptin therapy].

Herceptin has provided the first proof that tyrosine kinase modulation, through monoclonal antibodies can translate into improved clinical outcomes in cancer therapy. The development of Herceptin was encouraged by the biologic significance of HER2 overexpression. Although the number of patients affected by the targeted molecular abnormality(30% of breast cancer patients) is small and the response rate observed in patients after treated with single agent Herceptin is rather low, the ability to document overexpression of the target in breast biopsies, and a growing interest in biologic therapy facilitated the rapid accrual of patients to clinical trials. The challenges of applying research techniques of molecular biology to routine clinical testing have been demonstrated by the experiences with the HER2/neu oncogene. Immunohistochemistry and fluorescence in situ hybridization yielded discrepant results regarding the frequency and degree of HER2 alterations even within the same sample. In order to make the complexity of interpretation of the discrepancy simple, it is wise to build an algorithm to help clinicians follow the ideal sequence of laboratory testings. The experience gained in the testing of Herceptin has provided important lessons for the future testing of molecularly targeted compounds.

Animals↗