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Yamamoto D.,Kansai Medical University | Tsubota Y.,Kansai Medical University | Sueoka N.,Kansai Medical University | Yamamoto C.,Seiko Hospital | Kon M.,Kansai Medical University
Japanese Journal of Cancer and Chemotherapy | Year: 2015

The purpose of our study was to test the efficacy and toxicity of everolimus plus exemestane therapy for breast cancer. Between 2014 and 2015, 20 patients diagnosed with breast carcinoma were selected for this retrospective study. Patients received everolimus plus exemestane. As a result, 4 patients showed a partial response to treatment and the median PFS was 2.5 months (range, 1-9). The most common adverse events (AEs) associated with combination therapy were stomatitis, rash, dysgeusia, and noninfectious lung disease. The AEs reported were mostly grade 1 and 2, and manageable with appropriate intervention. Therefore, everolimus plus exemestane therapy for breast cancer seems to be effective and generally tolerable. Source


Yamamoto D.,Kansai Medical University | Iwase S.,University of Tokyo | Tsubota Y.,Kansai Medical University | Sueoka N.,Kansai Medical University | And 4 more authors.
OncoTargets and Therapy | Year: 2012

Background: Brain metastases from breast cancer occur in 20%-40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation. Methods: Five patients with brain metastases who did not respond to whole brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed. Results: The median time to disease progression was 86 days. Of five patients, two (40%) achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment related adverse events (all grades) were hypertension (60%), neuropathy (40%), and proteinuria (20%). No grade 3 toxicity was seen. No intracranial hemorrhage was observed. Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab. © 2012 Yamamoto et al, publisher and licensee Dove Medical Press Ltd. Source


Yamamoto D.,Kansai Medical University | Iwase S.,University of Tokyo | Yoshida H.,Kansai Medical University | Kuroda Y.,University of Tokyo | And 4 more authors.
Anticancer Research | Year: 2010

Background: S-1 is an orally administered fluorinated pyrimidine with high activity in metastatic breast carcinoma (MBC) and in chemotherapy-pretreated metastatic breast carcinoma. Patients and Methods: Forty patients with MBC who did not respond to capecitabine-based chemo-therapy and then received S-1 were identified from our data base of records between 2006 and 2008. The clinico-pathological data and outcomes of these patients were then reviewed. Results: The overall response rate was 27.8%. The median survival was 19.2 months, and the median time to disease progression was 6.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (15%), nausea (15%), vomiting (7.5%), disorder of taste (7.5%), and diarrhea (5%). However, the majority were mild to moderate in intensity, and only one patient experienced grade 3 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths. Conclusion: The results of the current study demonstrate that S-1 is an effective and well-tolerated treatment in patients with capecitabine-resistant MBC. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment. Source


Yamamoto D.,Kansai Medical University | Iwase S.,Tokyo Medical University | Tsubota Y.,Kansai Medical University | Ariyoshi K.,Tokyo Medical University | And 10 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015

Purpose: Capecitabine and S-1 are orally administered fluorinated pyrimidines with high-level activity against metastatic breast cancer (MBC). This randomized, multicenter, phase II study compared the activities and safeties of the oral fluoropyrimidines, capecitabine and S-1, in breast cancer patients. Methods: Patients with MBC were randomly assigned to receive capecitabine 825 g/m2 twice daily on days 1-21 every 4 weeks or S-1 40-60 mg twice daily, according to body surface area, on days 1-28 every 6 weeks. The primary endpoint was progression-free survival (PFS). Results: A total of 142 patients were enrolled and randomized to either capecitabine (N = 73) or S-1 (N = 69). Median PFS (progression-free survival) was 1.2 years for capecitabine and 1.3 years for S-1, with a hazard ratio (S-1/capecitabine) of 0.85 (95 % confidence interval [CI] 0.52-1.38) (P = 0.48 by log-rank). The confirmed objective response rates were 24.0 % for capecitabine and 23.1 % for S-1 (P = 0.938). The most common treatment-related adverse events were grade 1-2 in intensity. Thrombocytopenia (S-1: 9.2 %, capecitabine: 1.4 %; P = 0.040) and nausea (S-1: 26.2 %, capecitabine: 14.1 %; P = 0.079) were more frequent in the S-1 group, while hand-foot syndrome occurred more often in the capecitabine group (S-1: 10.8 %, capecitabine: 25.4 %; P = 0.029). Conclusions: The results of the current study demonstrate that both S-1 and capecitabine are effective and well-tolerated treatments in patients with MBC, while their adverse events were different. They are both convenient, orally administered drugs, making them attractive agents for use in outpatient treatment. © 2015 Springer-Verlag Berlin Heidelberg. Source


Yamamoto D.,Kansai Medical University | Iwase S.,University of Tokyo | Yoshida H.,Kansai Medical University | Kuroda Y.,University of Tokyo | And 4 more authors.
Anticancer Research | Year: 2011

Background: We reported that doxorubicin and cyclophosphamide (DC) followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. However, as one of the side effects of paclitaxel, neuropathy was noted in up to 30% of patients. Cyclooxygenase-2 (COX-2) and its derived prostaglandins play a role in stimulating angiogenesis, inhibiting apoptosis, and suppressing the immune response. Some recent studies showed that COX-2 inhibitors, such as meloxicam, have the potential to enhance tumor suppression and reduce the severity of paclitaxel-induced neuropathy. Patients and Methods: Four cycles of DC (doxorubicin: 60 mg/m 2 and cyclophosphamide: 600 mg/m 2) administered intravenously (i.v.) on day 1 every 21 days were followed by 12 cycles of paclitaxel i.v. (80 mg/m 2) every 7 days, prior to surgery. During paclitaxel therapy, breast cancer patients were administered meloxicam (10 mg per day) daily, when experiencing symptoms of grade 2 neuropathy (motor or sensory). The primary endpoint was the pCR rate achieved with the treatment. Results: Forty-three patients received preoperative chemotherapy between April 2004 and March 2007 at six centers. The patient population was identified from a database of the Japan Breast Cancer Research Network. Clinical responses were rated as clinically complete response (cCR) in 9 patients (22%), clinically partial response (cPR) in 25 patients (59%), and clinically stable disease (cSD) in 9 patients (19%). pCR was seen in 25.6%. In addition, we identified 15 patients, who developed grade 2 neuropathy during paclitaxel therapy and subsequently received meloxicam. Meloxicam application had a marked effect within 28 days of initiation. The sensory neuropathy of the patients was reduced gradually, but their motor neuropathy did not improve. Five out of the 15 patients with neuropathy experienced symptom improvement after meloxicam treatment (p<0.05; before versus after 2 months of meloxicam administration). Furthermore, among the 15 patients, who received meloxicam, clinical responses were rated as cCR in 2 patients, cPR in 4 patients, and cSD in 9 patients. The pCR was seen in 4 patients (26.7%). Conclusion: Although meloxicam in combination with DC and weekly paclitaxel chemotherapy did not show promising therapeutic activity, it may provide some relief for neuropathy. Source

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