Biomedical subjects

Naohito Yamamoto

Publications and source records attributed to Naohito Yamamoto.

11 recordsLinked to original sources

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

Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer.

PURPOSE: To evaluate the efficacy and tolerability of dofequidar plus cyclophosphamide, doxorubicin, and fluorouracil (CAF) therapy in comparison with CAF alone, in patients with advanced or recurrent breast cancer. Dofequidar is a novel, orally active quinoline derivative that reverses multidrug resistance. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled trial, patients were treated with six cycles of CAF therapy: 28 days/cycle, with doxorubicin (25 mg/m2) and fluorouracil (500 mg/m2) administered on days 1 and 8 and cyclophosphamide (100 mg orally [PO]) administered on day 1 through 14. Patients received dofequidar (900 mg PO) 30 minutes before each dose of doxorubicin. Primary end point was overall response rate (ORR; partial or complete response). In total, 221 patients were assessable. RESULTS: ORR was 42.6% for CAF compared with 53.1% for dofequidar + CAF, a 24.6% relative improvement and 10.5% absolute increase (P = .077). There was a trend for prolonged progression-free survival (PFS; median 241 days for CAF v 366 days for dofequidar + CAF; P = .145). In retrospectively defined subgroups, significant improvement in PFS in favor of dofequidar was observed in patients who were premenopausal, had no prior therapy, and were stage IV at diagnosis with an intact primary tumor. Except for neutropenia and leukopenia, there was no statistically significant excess of grade 3/4 adverse events compared with CAF. Treatment with dofequidar did not affect the plasma concentration of doxorubicin. CONCLUSION: Dofequidar + CAF was well tolerated and is suggested to have efficacy in patients who had not received prior therapy.

Adult↗

PubMed2006

Carotid angioplasty with stenting for chronic internal carotid artery occlusion: technical note.

INTRODUCTION: Carotid angioplasty with stenting (CAS) is becoming accepted as an effective and reliable treatment option for severe carotid artery stenosis. However, it is rarely applied for carotid occlusion, especially in its chronic stage. We report our experience of CAS for chronic internal carotid artery occlusion representing compromised cerebral blood flow using various protection methods. METHODS: A 77-year-old woman, who was already diagnosed with severe left internal carotid artery stenosis, suddenly had right hemiparesis and aphasia. At that time, she was treated conservatively because her neurological status was quite good, in spite of left carotid artery occlusion. Her symptoms improved in the short term, except slight aphasia, but deteriorated again 18 days from the onset, and magnetic resonance imaging (MRI) showed new ischemic lesions. CAS was then performed for the occluded carotid artery on the 23rd day from the first onset. RESULTS: Using the proximal protection technique, the occluded lesion was crossed carefully with a microguidewire. Stents were also placed successfully with the distal protection technique. The occluded carotid artery was completely recanalized without any unfavorable events or neurological deterioration. CONCLUSION: In this patient, CAS was successfully to treat chronic carotid artery occlusion. These procedures and techniques are reviewed and discussed.

Aged↗

PubMed2006

Two cases of adenoid cystic carcinoma: preoperative cytological findings were useful in determining treatment strategy.

Adenoid cystic carcinoma (ACC) of the breast is a rare variant of breast malignancy and is known to have an excellent prognosis. We report two cases of ACC diagnosed by preoperative fine-needle aspiration cytology (FNAC), which proved to be very useful in determining the appropriate treatment. The patients were a 57-year-old woman (case 1) and a 71-year-old woman (case 2). On physical examinations and imaging studies both tumors were recognized as lobulated tumors that measured 3.0 x 2.3 cm (case 1) and 3.9 x 3.4 cm (case 2) respectively. FNAC materials showed clusters of malignant cells surrounding globules of mucus, therefore, ACC was diagnosed. Considering the characteristics of ACC, breast-conserving surgeries with axillary dissection and adjuvant radiotherapy were performed instead of primary chemotherapy or mastectomy. Histologically, a distinctive biphasic pattern was observed that consisted of true laminae and pseudocystic spaces. Tumor sizes were 4.0 x 3.3 cm (case 1) and 4.6 x 3.8 cm (case 2), respectively, and surgical margins were negative on microscopic examination. Lymph node metastasis was not present in either case. Even though ACC is very rare, preoperative diagnosis can be made based on its characteristic features. Preoperative diagnosis is extremely useful for determining appropriate treatment.

Aged↗

PubMed2006

Combination docetaxel and trastuzumab treatment for patients with HER-2-overexpressing metastatic breast cancer: a multicenter, phase-II study.

BACKGROUND: Pre-clinical and clinical studies indicate that a combination of docetaxel and trastuzumab may effectively treat patients with human epidermal growth factor receptor-2 (HER-2) overexpressing metastatic breast cancer. We evaluated the efficacy and safety of this combination in a multicenter, open-label phase II study in Japan. METHODS: Women with metastatic breast cancer whose tumors overexpressed HER-2, as assessed by immunohistochemistry and by fluorescence in situ hybridisation, received 2 to 6 cycles of docetaxel (70 mg/m2, every 3 weeks) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). The primary endpoint was tumor response. Secondary endpoints were time to disease progression and adverse events. RESULTS: Of the 40 women enrolled in the study, 27 (68%) completed 6 cycles of treatment. Three patients discontinued the study before the second cycle. Median follow-up was 20.8 months (range, 0.6 to 30.9 months). The overall response rate was 65% (26/40; 95% CI, 48% to 79%). The median time to progression was 6.8 months (range, 0.6 to 21.2 months). Of the 40 patients, 35 (88%) had grade 3 or 4 leukopenia, and 33 (83%) had grade 3 or 4 neutropenia. Most instances of leukopenia and neutropenia were manageable by reducing the dose of docetaxel or by treatment with granulocyte colony-stimulating factor. In 4 patients, left ventricular ejection fraction decreased by more than 10% from baseline. CONCLUSIONS: The combination of docetaxel and trastuzumab was as effective as reported in other similar studies and was well tolerated in these patients.

Adult↗

PubMed2006

Analysis of non-genetic risk factors for adverse skin reactions to radiotherapy among 284 breast cancer patients.

OBJECTIVES: We analyzed non-genetic risk factors for adverse skin reactions to irradiation at 4 collaborating Japanese institutions, to design future investigation into genetic risk factors for adverse skin reactions to irradiation in a multicenter setting. METHODS: From April 2001, 284 breast cancer patients, who underwent radiotherapy with breast-conserving surgery, were enrolled from 4 collaborating institutions in Japan. We graded skin reactions according to international scoring systems. Clinical factors were tested against adverse effects. RESULTS: Grade 1+ skin reactions were observed in 261 (92%) of the patients in less than 3 months, 118 (42%) at 3 months, and 29 (10%) at 6 months in the late phase. Univariate analysis of treatment risk factors (such as the use of a multi-leaf colimeter, wedge-filter, or immobilization device) for skin reactions revealed a significant association (p< 0.0001). After a variable selection procedure with logistic regression, the institution, operative procedure, and magnitude of photon energy remained significantly associated with acute skin reactions. Only the institution was an explanatory variable for skin reactions at 3 and 6 months in the final logistic model. CONCLUSION: After stratification, substantial remaining variations in the occurrence of skin reactions of a given level suggested that individual genetic factors contribute markedly to individual radiosensitivity. Analysis of genetic factors associated with adverse effects would be possible by stratifying patients according to institution. Selection of eligible institutions, where appropriate treatment modalities could be performed, would also be possible when planning such a study.

Adult↗

PubMed2006

[Multicenter phase II trial of thrice-weekly docetaxel and weekly trastuzumab as preoperative chemotherapy in patients with HER 2-overexpressing breast cancer--Japan East Cancer Center Breast Cancer Consortium (JECBC) 02 Trial].

The efficacy and safety of combination therapy of 4 cycles with docetaxel 70 mg/m(2)every 3 weeks and trastuzumab as primary chemotherapy for operable breast cancer was determined in 21 patients (pts) by assessing the pathological complete response (pCR) rate, clinical response rate (RR), breast conservation surgery (BCS) rate and toxicities. To date, 19 pts have completed surgery. The pCR rate was 21% [95% CI 6%-46%] . The overall RR was 90% [95% CI 67%-99%] , with 5 CR, 12 PR, 2 SD and 0 PD. Grade 3 or 4 adverse events were leukopenia 48%, neutropenia 67%, hemoglobin 5%, and febrile neutropenia 10%. All non-hematological toxicities were mild and manageable. The pCR rate is not as low as that achieved in previous international studies. The combination of docetaxel and trastuzumab was a well-tolerated and very active regimen for the treatment of patients with HER 2-overexpressing operable breast cancer. This regimen promises to be one of the leading future treatments for progressive breast cancer.

Adult↗

PubMed2005

Long-term efficacy of hybrid pharmacologic and ablation therapy in patients with pilsicainide-induced atrial flutter.

BACKGROUND: Combination therapy with catheter ablation of the cavo-tricuspid isthmus and continued drug therapy, that is, "hybrid therapy," in patients with atrial fibrillation (AF) and drug-induced atrial flutter (AFL) is reported to be an alternative means of achieving and maintaining sinus rhythm. With respect to choosing this method among the rhythm control therapies, its long-term efficacy and the prevalence of AFL in patients with AF are very important and have not been fully elucidated. HYPOTHESIS: The purpose of this study was to investigate the long-term effectiveness of this hybrid therapy and the dose prevalence in Ic drug-induced AFL. METHODS: The subjects were 89 patients (aged 62.4 years, 72 men) with episodes of AF (paroxysmal type: 65, persistent type: 11, permanent type: 13). After 4 weeks of oral pilsicainide administration, the dose was increased in those with no documented AFL. The patients who experienced AFL with pilsicainide (Ic-AFL) underwent ablation. RESULTS: Pilsicainide administration resulted in the common type AFL in 17 patients (19.1%). The pilsicainide plasma concentration in the patients with Ic-AFL was significantly higher than in those without AFL (0.79 +/- 0.41 vs. 0.51 +/- 0.24 microg/ml, respectively, p < 0.01). During a 10-54 (mean 37 +/- 14) month follow-up period, sinus rhythm was maintained in 10 of 12 patients after successful ablation followed by continued antiarrhythmic drug administration. CONCLUSIONS: Hybrid therapy with ablation and high doses of pilsicainide was useful in maintaining sinus rhythm in some selected patients with AF and drug-induced AFL.

Aged↗

PubMed2004

Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter.

We examined the expression level of the midkine (MK) and c-erbB-2 genes in both tumorous and matched nontumorous specimens from 18 patients with breast cancer. Expression of the MK and c-erbB-2 genes in nontumorous regions was relatively low, and the expression levels of both genes were not markedly different among the nontumorous samples. In contrast, the expression of the MK and c-erbB-2 genes in tumorous specimens was upregulated in 18 and 6 specimens, respectively. Regulatory regions of the MK gene were able to activate a reporter gene to a similar degree as those of the c-erbB-2 gene in the human breast cancer cell lines tested. Transfection of breast cancer cells with either the MK promoter- or the c-erbB-2 promoter-linked herpes simplex virus thymidine kinase gene increased their sensitivity to the prodrug ganciclovir. These data showed that the MK promoter activated a therapeutic gene in a wider range of human breast cancer than the c-erbB-2 promoter and suggest that MK promoter-mediated gene therapy is potentially more favorable in clinical settings.

Adult↗

PubMed2003

Phyllodes tumor arising in ectopic breast tissue of the axilla.

We examined a 31-year-old woman with a solid mass in her left axilla. Physical examination and ultrasonography confirmed a 2 cm well-defined mass. Fine needle aspiration biopsy suggested fibroadenoma of breast. Excisional biopsy revealed benign phyllodes tumor of the ectopic breast tissue. Phyllodes tumor in ectopic breast tissue is an extremely rare occurrence. Only nine cases have been reported, including tumors of the vulva, inguinal region and axilla. This is the second case in the axillary region.

Adult↗

PubMed2002

Will subareolar injection be a standard technique for sentinel lymph node biopsy?

BACKGROUND: Controversy surrounds the correct injection site of radioisotope (RI) and blue dye for sentinel node biopsy (SNB) in breast cancer, and there have been some reports on the advantages of subareolar (SA) injection. We carried out a study to assess whether SA injection is useful for all patients undergoing SNB. METHODS: In this prospective study, 20 patients with T1 or T2 tumors clinically node negative, were enrolled. Injection of 99mTc-phytate (0.5 mCi) was performed two times (3 to 5 days before surgery and the day of surgery) for each patient. The first RI injection was SA, and the second RI injection was subdermal (SD). The location and number of hot nodes were assessed by lymphoscintigraphy (LSG) and hand-held gamma probe. RESULTS: There were no patients in whom hot nodes on LSG were visualized in clearly different locations between the SA and SD injection sites. However, there were 2 patients in whom hot nodes were identified at different locations with a gamma probe. Seven patients had more hot nodes on LSG with SD injection than SA injection. Eight patients had a higher RI count of hot nodes by SD injection than SA injection. The mean RI count of hot nodes by SA injection was higher than that after SD injection. CONCLUSION: SA and SD lymphatic flow run into the same node in most patients, however, SD injection is more useful than SA injection in some patients. Though SA injection is a useful technique, it may not identify sentinel lymph nodes correctly in patients with multiple lesions or tumors in the upper outer quadrant.

Aged↗