Sagara Hospital

Kagoshima-shi, Japan

Sagara Hospital

Kagoshima-shi, Japan

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PubMed | National Hospital Organization Osaka National Hospital, Shizuoka Cancer Center, Juntendo University, Aichi Cancer Center Hospital and 8 more.
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2016

The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer.Patients were randomized to either low-dose XT (capecitabine 825mg/mIn total, 162 patients were treated. Median PFS was 10.5months with low-dose XT and 9.8months with single-agent docetaxel (hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.40-0.97]; p=0.03). The OS HR was 0.89 (95% CI 0.52-1.53; p=0.68). Grade 3 treatment-related toxicities occurred in 74% of XT-treated patients and 76% of docetaxel-treated patients. The main differences in grade 3 treatment-related toxicities were hand-foot syndrome (7.3% of XT-treated patients vs 0% receiving docetaxel), fatigue/malaise (2.4 vs 10.0%), and peripheral edema (1.2 vs 7.5%). Dose modifications were required in 100% of low-dose XT and 49% of docetaxel patients. Toxicity-related treatment discontinuations occurred in 18 and 33%, respectively.The improved PFS with low-dose XT versus docetaxel alone is consistent with higher-dose XT phase III experience, but the safety profile was more favorable and manageable.


PubMed | Miyara Clinic, Hirosaki National Hospital, Nagumo Clinic Fukuoka, Shonan Memorial Hospital and 4 more.
Type: Journal Article | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2015

Cancer-related fatigue (CRF) is one of the most common symptoms reported by cancer patients. This randomized trial investigated the efficacy of the amino acid jelly Inner Power() (IP), a semi-solid, orally administrable dietary supplement containing coenzyme Q10 and L-carnitine, in controlling CRF in breast cancer patients in Japan.Breast cancer patients with CRF undergoing chemotherapy were randomly assigned to receive IP once daily or regular care for 21 days. The primary endpoint was the change in the worst level of fatigue during the past 24 h (Brief Fatigue Inventory [BFI] item 3 score) from day 1 (baseline) to day 22. Secondary endpoints were change in global fatigue score (GFS; the average of all BFI items), anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HADS), quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific QLQ (EORTC QLQ-BR23), and adverse events.Fifty-nine patients were enrolled in the study, of whom 57 were included in the efficacy analysis. Median patient age was 50 years. Changes in the worst level of fatigue, GFS, and current feeling of fatigue were significantly different between the intervention and control groups, whereas the change in the average feeling of fatigue was not significantly different between groups. HADS, EORTC QLQ-C30, and EORTC QLQ-BR23 scores were not significantly different between the two groups. No severe adverse events were observed.IP may control moderate-severe CRF in breast cancer patients.The registration number of this study in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) is UMIN000008646.


Yumimoto K.,Kyushu University | Akiyoshi S.,Kyushu University | Ueo H.,Kyushu University | Sagara Y.,Sagara Hospital | And 6 more authors.
Journal of Clinical Investigation | Year: 2015

The gene encoding F-box protein FBXW7 is frequently mutated in many human cancers. Although most previous studies have focused on the tumor-suppressive capacity of FBXW7 in tumor cells themselves, we determined that FBXW7 in the host microenvironment also suppresses cancer metastasis. Deletion of Fbxw7 in murine BM-derived stromal cells induced accumulation of NOTCH and consequent transcriptional activation of Ccl2. FBXW7-deficient mice exhibited increased serum levels of the chemokine CCL2, which resulted in the recruitment of both monocytic myeloid-derived suppressor cells and macrophages, thereby promoting metastatic tumor growth. Administration of a CCL2 receptor antagonist blocked the enhancement of metastasis in FBXW7-deficient mice. Furthermore, in human breast cancer patients, FBXW7 expression in peripheral blood was associated with serum CCL2 concentration and disease prognosis. Together, these results suggest that FBXW7 antagonizes cancer development in not only a cell-autonomous manner, but also a non-cell-autonomous manner, and that modulation of the FBXW7/NOTCH/CCL2 axis may provide a potential approach to suppression of cancer metastasis.


Iwata H.,Aichi Cancer Center Hospital | Masuda N.,National Hospital Organization | Sagara Y.,Sagara Hospital | Kinoshita T.,National Cancer Center Hospital | And 10 more authors.
Cancer | Year: 2013

Background: The increasing costs associated with large-scale adjuvant trials mean that the prognostic value of biologic markers is increasingly important. The expression of nuclear antigen Ki-67, a marker of cell proliferation, has been correlated with treatment efficacy and is being investigated for its value as a predictive marker of therapeutic response. In the current study, the authors explored correlations between Ki-67 expression and tumor response, estrogen receptor (ER) status, progesterone receptor (PgR) status, and histopathologic response from the STAGE study (S-tudy of T-amoxifen or A-rimidex, combined with G-oserelin acetate to compare E-fficacy and safety). METHODS: In a phase 3, double-blind, randomized trial (National Clinical Trials identifier NCT00605267), premenopausal women with ER-positive, early stage breast cancer received either anastrozole plus goserelin or tamoxifen plus goserelin for 24 weeks before surgery. The Ki-67 index, hormone receptor (ER and PgR) status, and histopathologic responses were determined from histopathologic samples that were obtained from core-needle biopsies at baseline and at surgery. Tumor response was determined by using magnetic resonance imaging or computed tomography. RESULTS: In total, 197 patients were randomized to receive either anastrozole plus goserelin (n = 98) or tamoxifen plus goserelin (n = 99). The best overall tumor response was better for the anastrozole group compared with the tamoxifen group both among patients who had a baseline Ki-67 index ≥20% and among those who had a baseline Ki-67 index <20%. There was no apparent correlation between baseline ER status and the Ki-67 index in either group. Positive PgR status was reduced from baseline to week 24 in the anastrozole group. CONCLUSIONS: In premenopausal women with ER-positive breast cancer, anastrozole produced a greater best overall tumor response compared with tamoxifen regardless of the baseline Ki-67 index. © 2012 American Cancer Society.


Iwata H.,Aichi Cancer Center Hospital | Masuda N.,Osaka National Hospital | Ohno S.,National Kyushu Cancer Center | Rai Y.,Sagara Hospital | And 9 more authors.
Breast Cancer Research and Treatment | Year: 2013

The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced, hormone-receptor-positive breast cancer. This phase 3, randomized, double-blind study directly compared time to progression (TTP) for exemestane and anastrozole therapy in this patient population. Eligible patients were randomized to receive exemestane 25 mg or anastrozole 1 mg, each once daily. The primary endpoint was TTP based on assessment by an expert radiologic images review committee (ERIRC). Secondary endpoints included investigator-assessed TTP, time to treatment failure, overall survival, objective response rate, clinical benefit rate, and safety. A total 298 patients were randomized to receive exemestane (n = 149; mean age 63.4 years) or anastrozole (n = 149; mean age 64.0 years). Median ERIRC-assessed TTP was 13.8 and 11.1 months (hazard ratio = 1.007; 95 % confidence interval [CI]: 0.771, 1.317) and median investigator-assessed TTP was 13.8 and 13.7 months (hazard ratio = 1.059; 95 % CI: 0.816, 1.374) in the exemestane and anastrozole arms, respectively. Median overall survival was 60.1 months in the anastrozole arm and was not reached in the exemestane arm at data cutoff. The objective response rate was 43.9 % (95 % CI: 35.3, 52.8) and 39.1 % (95 % CI: 30.6, 48.1) in the exemestane and anastrozole arms, respectively. Treatment-related adverse events grade ≥3 occurred in 9.4 and 6.0 % of patients, and treatment-related serious adverse events occurred in 4.0 and 3.4 % of patients in the exemestane and anastrozole arms, respectively. In this study, the efficacy and safety profiles of exemestane were similar to those of anastrozole in Japanese patients with advanced, hormone-receptor-positive breast cancer; however, TTP non-inferiority of exemestane versus anastrozole was not confirmed. © 2013 The Author(s).


Aogi K.,Shikoku Cancer Center | Yoshida M.,Seirei Hamamatsu General Hospital | Sagara Y.,Sagara Hospital | Kamigaki S.,Sakai Municipal Hospital | And 6 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Purpose: Gemcitabine (GEM)-paclitaxel combination therapy has been confirmed as a standard therapy for metastatic/recurrent breast cancer (MBC) in Western countries. This study was conducted to assess the efficacy and safety of GEM-paclitaxel combination therapy in Japanese MBC patients. Methods: Patients were administered paclitaxel 175 mg/m2 on day 1, and GEM 1,000 or 1,250 mg/m2 on days 1 and 8 of 21-day cycle. The primary endpoint of this study was overall response rate; secondary endpoints were duration of response, time to progression, survival time and rate. Results: Paclitaxel 175 mg/m2 plus GEM 1,250 mg/m2 was determined as the recommended dose. A total of 56 patients received 506 cycles of treatment (median: 7.5 cycles) with a relative dose intensity of 79.6% for GEM and 85.8% for paclitaxel. The response rate was 44.6% (25/56 patients), median time to progression 8.6 months and median survival time 27.1 months. In triple-negative patients, the response rate was 35.7% (5/14 patients), and the median time to progression was 6.0 months. The most frequent grade ≥ 3 toxicities were neutropenia (82.1%), leukopenia (62.5%) and ALT increase (14.3%). Conclusions: This study confirmed the efficacy and safety of GEM-paclitaxel combination therapy in Japanese MBC patients. © 2010 Springer-Verlag.


Shibuta K.,Ueo Breast Surgical Hospital | Ueo H.,Ueo Breast Surgical Hospital | Furusawa H.,Breastopia Namba Hospital | Komaki K.,Breastopia Namba Hospital | And 4 more authors.
Breast Cancer | Year: 2011

Background: Estrogen receptor (ER), progesterone receptor (PgR), and HER2 expression status in breast cancer function as prognostic and predictive factors that enable individualized treatment. Intrinsic subtype classification has also been performed based on these and other biological and prognostic characteristics. However, clinical analysis of such subtypes in a large number of Japanese breast cancer patients has not yet been reported. Methods: Between January 2003 and December 2007, 4,266 patients with primary breast cancer were registered. Four subtypes based on immunohistochemically evaluated ER/PgR/HER2 status, clinicopathological features, and prognosis were analyzed retrospectively. Results: The following subtype distribution was observed: luminal A type (ER+ and/or PgR+, HER2-), 3,046 cases (71%); luminal B type (ER+ and/or PgR+, HER2+), 321 cases (8%); HER2 type (ER-, PgR-, HER2+), 398 cases (9%); and triple negative (TN) type (ER-, PgR-, HER2-), 501 cases (12%). The HER2+ subtypes (luminal B and HER2 types) had a significantly higher incidence of lymph node metastasis and lymphatic permeation, while the hormone receptor negative subtypes (HER2 and TN types) showed a significantly higher nuclear grade. Overall, patients with HER2-type and TN-type disease had a significantly poorer prognosis than other subtypes. Conclusion: Intrinsic breast cancer subtypes are associated with clinicopathological features and prognosis in Japanese women. Long-term clinical observation of the relationship between each subtype and therapies used should provide useful information for selecting appropriately tailored treatments. © 2010 The Japanese Breast Cancer Society.


Ohno S.,National Kyushu Cancer Center | Rai Y.,Sagara Hospital | Iwata H.,Aichi Cancer Center Hospital | Yamamoto N.,Chiba Cancer Center | And 7 more authors.
Annals of Oncology | Year: 2010

Background: FINDER1 compared efficacy, tolerability and pharmacokinetics (PK) of three fulvestrant dose regimens in postmenopausal Japanese women with estrogen receptor (ER)-positive locally advanced/metastatic breast cancer recurring or progressing after prior endocrine therapy. Patients and methods: The primary end point of this randomised, multicentre, phase II study was objective response rate (ORR) and the secondary end points included time to progression (TTP), clinical benefit rate (CBR), PK profiles and tolerability. Postmenopausal women with ER-positive advanced breast cancer were randomised to 28-day cycles of fulvestrant approved dose (AD), loading dose (LD) or high dose (HD) until disease progression.Results: Hundred and forty-three patients (median age 61 years) received fulvestrant AD (n = 45), LD (n = 51) or HD (n = 47). ORR was similar across dose regimens: 11.1%, 17.6% and 10.6% for AD, LD and HD, respectively, with overlapping confidence intervals. TTP and CBR were also similar between groups (median TTP: 6.0, 7.5 and 6.0 months, respectively; CBR: 42.2%, 54.9% and 46.8% for AD, LD and HD, respectively). Cmax and area under the plasma concentration-time curve were dose proportional and PK steady state was reached earlier with LD and HD than with AD. All three doses were well tolerated, with a similar adverse-event profile and no emerging safety concerns.Conclusion: Fulvestrant AD, LD and HD had similar efficacy and tolerability profiles in postmenopausal Japanese women with ER-positive advanced breast cancer. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


PubMed | National Cancer Center Hospital East, Shiga Medical Center for Adults, National Defense Medical College, Okayama University and 7 more.
Type: | Journal: Breast cancer (Tokyo, Japan) | Year: 2016

Sentinel lymph node biopsy (SLNB) alone has been compared with SLNB followed by axillary lymph node dissection (ALND) in sentinel lymph node (SLN)-positive breast cancer patients in randomized phase III trials: the addition of ALND did not further improve the patients outcome. However, there is still some controversy, regarding the clinical application of SLNB alone. To identify the optimal axillary treatment in the era of SLNB, the Japanese Breast Cancer Society conducted a group study of SLNB in 2014.A questionnaire on axillary surgery and radiation therapy was sent to 432 Japanese institutes in December 2014, and 309 (72%) completed the questionnaire.SLNB was performed at 98% of the institutes, and 77% offered irradiation for cancer treatment. Regarding breast-conserving surgery (BCS), SLNB alone was indicated at 41% of the institutes in the cases of SLN with micrometastases. However, in the cases of SLN with macrometastases, ALND was performed at 64%. The proportion of ALND seemed to be higher in total mastectomy than in BCS regardless of the SLN-positive status. In the cases of SLN with micrometastases, the radiation field was localized in the conserved breast at about half of the institutes. On the other hand, in the cases of SLN with macrometastases, it was extended to axillary and/or supraclavicular lesions beyond the conserved breast at about 70% of the institutes.Japanese breast physicians were conservative with respect to the omission of ALND in SLN-positive breast cancer, especially in the cases of SLN with macrometastases.


Masuda N.,National Hospital Organization | Sagara Y.,Sagara Hospital | Kinoshita T.,National Cancer Center Hospital | Iwata H.,Aichi Cancer Center Hospital | And 7 more authors.
The Lancet Oncology | Year: 2012

Background: Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer. We aimed to assess the efficacy and safety of anastrozole versus tamoxifen in premenopausal women receiving goserelin for early breast cancer in the neoadjuvant setting. Methods: In this phase 3, randomised, double-blind, parallel-group, multicentre study, we enrolled premenopausal women with oestrogen receptor (ER)-positive, HER2-negative, operable breast cancer with WHO performance status of 2 or lower. Patients were randomly assigned (1:1) to receive goserelin 3·6 mg/month plus either anastrozole 1 mg per day and tamoxifen placebo or tamoxifen 20 mg per day and anastrozole placebo for 24 weeks before surgery. Patients were randomised sequentially, stratified by centre, with randomisation codes. All study personnel were masked to study treatment. The primary endpoint was best overall tumour response (complete response or partial response), assessed by callipers, during the 24-week neoadjuvant treatment period for the intention-to-treat population. The primary endpoint was analysed for non-inferiority (with non-inferiority defined as the lower limit of the 95% CI for the difference in overall response rates between groups being 10% or less); in the event of non-inferiority, we assessed the superiority of the anastrozole group versus the tamoxifen group. We included all patients who received study medication at least once in the safety analysis set. We report the primary analysis; treatment will also continue in the adjuvant setting for 5 years. This trial is registered with . ClinicalTrials.gov, number . NCT00605267. Findings: Between Oct 2, 2007, and May 29, 2009, 204 patients were enrolled. 197 patients were randomly assigned to anastrozole (n=98) or tamoxifen (n=99), and 185 patients completed the 24-week neoadjuvant treatment period and had breast surgery (95 in the anastrazole group, 90 in the tamoxifen group). More patients in the anastrozole group had a complete or partial response than did those in the tamoxifen group during 24 weeks of neoadjuvant treatment (anastrozole 70·4% [69 of 98 patients] . vs tamoxifen 50·5% [50 of 99 patients]; estimated difference between groups 19·9%, 95% CI 6·5-33·3; p=0·004). Two patients in the anastrozole group had treatment-related grade 3 adverse events (arthralgia and syncope) and so did one patient in the tamoxifen group (depression). One serious adverse event was reported in the anastrozole group (benign neoplasm, not related to treatment), compared with none in the tamoxifen group. Interpretation: Given its favourable risk-benefit profile, the combination of anastrozole plus goserelin could represent an alternative neoadjuvant treatment option for premenopausal women with early-stage breast cancer. Funding: AstraZeneca. © 2012 Elsevier Ltd.

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