Morihiko Kimura

Gunma Prefectural Cancer Center, Maebashi, Gunma Prefecture, Japan

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Publications (25)49.71 Total impact

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    ABSTRACT: BACKGROUND: Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. PATIENTS AND METHODS: The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. RESULTS: A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. CONCLUSION: Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.
    Breast Cancer 09/2012; · 1.33 Impact Factor
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    ABSTRACT: The potential long-term adverse effects on quality of life have to be considered when selecting agents for adjuvant hormonal treatment for postmenopausal patients with estrogen receptor-positive breast cancer. We performed a 2-year multicenter randomized study to assess the differences in the time course effects between toremifene (TOR) and anastrozole (ANA) on serum lipid profiles and bone metabolism. This study assessed the serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (Apo A1), and apolipoprotein B (Apo B) as lipid profiles and bone-specific alkaline phosphatase (BAP) and the N-telopeptide of type-I collagen (NTX) as bone turnover markers in patients who received daily doses of 40 mg and 1 mg for TOR and ANA, respectively. A decreased serum level of TC, LDL-C, and Apo B was, respectively, observed at 6 months in 6.2, 12.9, and 13.8% of the patients who received TOR compared with the baseline. These decreases were maintained for at least 24 months. These lipid levels were not changed in those who received ANA. In the TOR patients, there was an increase in the serum level of HDL-C and Apo A1 at 6 months in 17.1 and 16.3%, respectively, which was maintained for at least 24 months, whereas these levels were almost stable in the patients who received ANA. Serum BAP decreased by 12.1% at 12 months and further decreased at 24 months and the serum NTX decreased by 22.0% at 6 months, which was maintained for at least 24 months in the patients who received TOR. In contrast, the serum BAP was increased by 26.0% at 6 months and by 29.2% at 12 months and the serum NTX increased by 21.3% at 24 months compared with baseline in those received ANA. However, the serum BAP increase was not significant at 24 months. TOR provides better effects than ANA in terms of lipid profiles and bone metabolism in postmenopausal females with early breast cancer.
    Breast Cancer Research and Treatment 06/2011; 128(3):775-81. · 4.47 Impact Factor
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    ABSTRACT: Toremifene and tamoxifen have been used for adjuvant therapy in post-menopausal patients with breast cancer in Japan. Dyslipidemias are common in post-menopausal women. However, limited data are available on the effects of these agents on lipid profiles in Japanese patients. The Japan Toremifene Cooperative Study Group has been conducting a Phase III randomized trial of post-menopausal patients with breast cancer. One of its secondary endpoints is to confirm the effects of these agents on serum lipid profiles. The subjects were post-menopausal Japanese patients who had undergone surgery for early breast cancer. Toremifene or tamoxifen was administered for 2 years. Lipid levels were measured before and up to 24 months after initiation. Compared with baseline, at 24 months, the toremifene group (n = 123) showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001), and significantly increased high-density lipoprotein cholesterol levels (P < 0.001). Their triglyceride levels were not affected (P = 0.677). The tamoxifen group (n = 120) also showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001); no significant changes occurred in high-density lipoprotein cholesterol (P = 0.297) or triglyceride levels (P = 0.120). Distinct differences between two selective estrogen receptor modulators on lipids were observed. Toremifene improved lipid profiles, particularly as an enhancer of high-density lipoprotein cholesterol. To a large extent, tamoxifen improved low-density lipoprotein cholesterol levels. The impact of these improved lipid profiles on the risk of cardiovascular diseases needs further confirmation.
    Japanese Journal of Clinical Oncology 04/2010; 40(7):627-33. · 1.90 Impact Factor
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    ABSTRACT: A multicenter, phase II study was conducted to evaluate the efficacy and safety of the Japanese intermittent 4-week regimen of capecitabine in patients with advanced/metastatic breast cancer. Fifty patients who had received no more than one prior chemotherapy regimen for advanced/metastatic disease were enrolled from 23 centers and received at least two 4-weekly cycles of capecitabine (828 mg/m² orally twice daily for 3 weeks followed by a 1-week rest period). The overall response rate assessed by the Independent Review Committee (standard population, n = 46) was 28.3% (95% confidence interval 16.0-43.5%), including complete responses in 6.5%. Stable disease was observed in 20 patients and maintained for more than 6 months in 10 patients. The median duration of response in 13 evaluable responders was 5.3 months. Among evaluable patients (n = 47), median time to disease progression was 5.1 months. Median overall survival was 20.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (66%), nausea (26%), stomatitis (22%) and diarrhea (20%). Grade 3/4 treatment-related adverse events were seen in 23 patients (46%). The most common grade 3/4 adverse events were lymphocytopenia (22%), hand-foot syndrome (18%) and hyperbilirubinemia (10%). Although the target overall response rate was not reached, the Japanese intermittent 4-week regimen of capecitabine was shown to be an effective and well-tolerated first- or second-line therapy for advanced/metastatic breast cancer.
    Breast Cancer 08/2009; 17(4):233-40. · 1.33 Impact Factor
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    ABSTRACT: To compare the cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and the anthracycline-containing regimen cyclophosphamide, epirubicin, and fluorouracil (CEF) to evaluate the efficacy and safety of the latter. A total of 294 patients with axillary node-positive primary breast cancer of STAGE I-IIIa were randomly assigned to either CEF [cyclophosphamide (CPA) 500 mg/m(2) i.v. days 1 and 8; epirubicin (EPI) 60 mg/m(2) i.v. day 1; and 5-fluorouracil (5-FU) 500 mg/m(2) i.v. days 1 and 8] or CMF [CPA 500 mg/m(2) i.v. days 1 and 8; methotrexate (MTX) 40 mg/m(2) i.v. days 1 and 8; and 5-FU 500 mg/m(2) i.v. days 1 and 8]. Both treatment regimens were comprised of six cycles at 4-week intervals. Tamoxifen (TAM) 20 mg/day was concomitantly given to estrogen receptor (ER)-positive patients and those with undetermined ER status for 2 years. The overall 5-year survival was 77.1% for CEF and 71.4% for CMF [p = 0.24; hazard ratio 0.79 (95% CI 0.50-1.24)], and the 5-year disease-free survival was 55.7% for CEF and 48.9% for CMF [p = 0.15; hazard ratio 0.80 (95% CI 0.57-1.12)]. Although the log-rank test did not show a significant difference, both overall and disease-free survivals were higher for CEF according to the point estimates. Adverse drug reactions (ADRs) occurred more frequently in CEF. Whereas CEF had a good trend compare with CMF, it could not be proven statistically significant. The principal cause of the failure seems to be insufficient power, that is, the dose intensity (EPI: 60 mg/m(2)) set 10 years ago, when the trial began, was low, and the number of trial subjects was small because of the background of the times, which made the accumulation of cases extremely difficult. However, the trial should be considered to be meaningful, as it was the first, formally conducted controlled trial on chemotherapy in Japan.
    Breast Cancer 08/2009; 17(3):190-8. · 1.33 Impact Factor
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    ABSTRACT: We conducted a phase II study to determine the availability and safety of combination chemotherapy with weekly paclitaxel and doxifluridine (a capecitabine metabolite) in the treatment of advanced or recurrent breast cancer. Patients were treated with a combination chemotherapy regimen: doxifluridine was orally administered at 800 mg/day for 14 days, followed by a 7-day washout period. Paclitaxel was given intravenously on days 1 and 8 at 80 mg/m2 for 1 h, followed by a 1-week washout period. This 3-week cycle of therapy was repeated as long as possible (at least eight cycles) until the progression of the tumor and drug-related adverse effects were no longer observed. From May 2003 to December 2005, 26 patients were enrolled in the study. The overall response rate was 53.8% (95% confidence interval, 33.4-73.4%). The clinical benefit rate, including long-term no change, was 65.4% (95% confidence interval, 44.3-82.8%). Time to progression and survival time were 297 and 1182 days, respectively, for the 26 enrolled patients. No severe toxicities were observed. Grade 3/4 leucopenia in three patients, neutropenia in five patients, increased serum creatinine in three patients, hypercalemia in one patient, hypocalcemia in one patient, nausea/vomiting in two patients, and diarrhea in one patient. The good response rate and long time to progression and overall survival time of this doxifluridine combined with weekly paclitaxel therapy indicate its potential as a first-line or second-line treatment for advanced or recurrent breast cancer patients.
    Anti-Cancer Drugs 11/2008; 19(9):911-5. · 2.23 Impact Factor
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    ABSTRACT: To determine the efficacy of preoperative weekly paclitaxel for patients with operable breast cancer tumors greater than 3 cm. Paclitaxel 80 mg/m2 weekly x 3 times every 4 weeks for 3 cycles was administered to 53 patients. Twenty-two patients were stage 11, 26 stage III, 5 stage IV Median age (range) was 53 (24-73) years, and 32 patients were negative for estrogen receptor. Thirteen patients showed HER2 overexpression. Eligible cases composed of 53 patients for evaluation of response. Seven patients had a clinical complete response and 29 patients had a partial response. The overall response rate was 67.9%, including three patients with a pathological complete response. In 18 patients with HER2 overexpression, a clinical complete response was observed in 5, a partial response was observed in 9, and stable disease was found in 4. No treatment, related to grade 3 neutropenia, was given for 1 patient (2%). Other hematological and non-hematological toxicity was found in only 1 patient with fatigue. Preoperative weekly paclitaxel induced a high clinical response rate with a high safety profile. HER2-overepressing tumors had a higher clinical response rate than non-HER2-overepxressing tumors (91% vs. 50%, respectively). Further studies are needed to determine whether an increase in the cycles of paclitaxel and/or adding anthracyclines may lead to higher pathological complete response and breast-conservation rates in the neoadjuvant setting.
    Anticancer research 01/2008; 28(2B):1239-44. · 1.71 Impact Factor
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    ABSTRACT: Annual recurrence rates (ARR) are used to assess changes in the risk of breast cancer recurrence following surgery. In this retrospective study, ARR were calculated from the clinical records of 2,209 breast cancer patients who had undergone surgery. The time-course changes of ARR associated with prognostic/predictive factors were calculated. Overall, ARR decreased for 5 years following surgery and then remained almost constant. In hormone receptor (HR)-negative patients, ARR peaked after 2 years and peaked again at 6-7 years. In HR-positive patients, ARR peaked at 2 years. ARR increased in relation to the number of lymph-node metastases for 5 years, and peaked after 2 years in the absence and presence of venous invasion. The log-rank test demonstrated significant differences in recurrence between HR-negative and HR-positive cancer up to 5 years post-surgery. The presence of venous invasion had a significant effect on recurrence in the first 5 years, and the presence of lymph-node metastasis had a significant effect on recurrence up to and after 5 years. In conclusion, prognostic/predictive factors affected breast cancer recurrence in the first 5 years but had a lesser effect on recurrence more than 5 years post-surgery.
    Breast Cancer Research and Treatment 01/2008; 106(3):407-11. · 4.47 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the efficacy and predictive biomarkers of combination docetaxel-trastuzumab in a neoadjuvant setting by means of a phase II trial. Women with histologically-confirmed advanced invasive breast cancer whose tumours overexpressed HER-2 received 4 cycles of docetaxel (70 mg/m2 every 3 weeks) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). Twenty-one patients were enrolled, and all completed 4 cycles of treatment. Two patients were later found to be inoperable, and neither pathological nor clinical response was assessed. The pathological complete response rate was 21% (4/19; 95% CI, 6-46%) and the overall clinical response rate 89% (17/19; 95% CI, 67-99%). The relationship between the expression of biomarkers (HER-2, c-MYC, BRCA1 and Ki-67) and pathological response was assessed. The results suggested the possibility that tumours showing a high signal ratio of HER-2/CEP17 or c-MYC/CEP17 might be more sensitive to this combination therapy. Based on these results, it can be speculated that approximately 30% pCR might be obtained in cases with a high signal ratio of HER2/CEP17 or c-MYC/CEP17. Further trials are needed.
    Molecular Medicine Reports 01/2008; 1(1):71-5. · 1.17 Impact Factor
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    ABSTRACT: 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.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2006; 33(10):1411-5.
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    ABSTRACT: 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. 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. 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. The combination of docetaxel and trastuzumab was as effective as reported in other similar studies and was well tolerated in these patients.
    Breast Cancer 02/2006; 13(2):166-71. · 1.33 Impact Factor
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    ABSTRACT: The Y-box binding protein 1 (YB-1) regulates expression of P-glycoprotein encoded by the MDR1 gene. There have been no previous studies regarding the involvement of YB-1 in the development of resistance to paclitaxel. The present study was done to examine how paclitaxel affects the localization and expression of YB-1 in breast cancer. We evaluated the expression and localization of YB-1 and P-glycoprotein in breast cancer tissues obtained from 27 patients before and after treatment with paclitaxel. The effect of paclitaxel on localization of cellular YB-1 was examined by using GFP-YB-1. Interaction of YB-1 with the Y-box motif of the MDR1 promoters was studied by electrophoretic mobility shift assay. The effects of paclitaxel on MDR1 promoter activity were examined by luciferase assay. Of 27 breast cancer tissues treated with paclitaxel, nine (33%) showed translocation of YB-1 from the cytoplasm to the nucleus together with increased expression of P-glycoprotein during the course of treatment. Twelve breast cancer tissues (44%) showed neither translocation of YB-1 nor increased expression of P-glycoprotein. Nuclear translocation of YB-1 was correlated significantly with increased expression of P-glycoprotein (P=0.0037). Confocal analysis indicated that paclitaxel induced nuclear translocation of green fluorescent fused YB-1 in MCF7 cells. Furthermore, binding of YB-1 to the Y-box of MDR1 promoter was increased in response to treatment with paclitaxel. In addition, MDR1 promoter activity was significantly up-regulated by paclitaxel in MCF7 cells (P<0.001). The results of the present study suggested that YB-1 may be involved in the development of resistance to paclitaxel in breast cancer.
    Clinical Cancer Research 01/2006; 11(24 Pt 1):8837-44. · 7.84 Impact Factor
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    ABSTRACT: A late phase II clinical study (II) of a novel vinca alkaloid derivative KW-2307 (vinorelbine ditartrate) in advanced/recurrent breast cancer patients was performed at 22 institutions throughout Japan. An intravenous dose of KW-2307, 20 mg/m2, was administered once a week. Of the 60 patients enrolled in the study, 58 were eligible and 56 were evaluable. The response rate was 33.9% (19/56; 95% confidence interval: 21.8 to 47.8%) with one CR and 18 PRs. The response rate was as high as 37.0% (17/46; 95% confidence interval: 23.2 to 52.5%) when KW-2307 was used as a first-line chemotherapy for advanced/recurrent disease. The most common adverse event was myelosuppression including leukopenia in 96.4% (54/56) and neutropenia in 94.3% (50/53). Other events observed were increased GOT in 51.8% (29/56), increased GPT in 55.4% (31/56), LDH increased in 50.0% (27/54), serum total protein decrease in 39.3% (22/56), anorexia in 41.1% (23/56), nausea and vomiting in 66.1% (37/56), constipation in 30.4% (17/56), alopecia in 33.9% (19/56) and general fatigue in 46.4% (26/56). None of them were serious. This study demonstrated that KW-2307 was an effective and safe treatment for advanced/recurrent breast cancer patients.
    Gan to kagaku ryoho. Cancer & chemotherapy 08/2005; 32(7):983-90.
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    ABSTRACT: At present, it is one of the most important issues for the treatment of breast cancer to develop the standard therapy for patients previously treated with anthracyclines and taxanes. With the objective of determining the usefulness of vinorelbine monotherapy in patients with advanced or recurrent breast cancer after standard therapy, we evaluated the efficacy and safety of vinorelbine in patients previously treated with anthracyclines and taxanes. Vinorelbine was administered at a dose level of 25 mg/m(2) intravenously on days 1 and 8 of a 3 week cycle. Patients were given three or more cycles in the absence of tumor progression. A maximum of nine cycles were administered. The response rate in 50 evaluable patients was 20.0% (10 out of 50; 95% confidence interval, 10.0-33.7%). Responders plus those who had minor response (MR) or no change (NC) accounted for 58.0% [10 partial responses (PRs) + one MR + 18 NCs out of 50]. The Kaplan-Meier estimate (50% point) of time to progression (TTP) was 115.0 days. The response rate in the visceral organs was 17.3% (nine PRs out of 52). The major toxicity was myelosuppression, which was reversible and did not require discontinuation of treatment. The results of this study show that vinorelbine monotherapy is useful in patients with advanced or recurrent breast cancer previously exposed to both anthracyclines and taxanes.
    Japanese Journal of Clinical Oncology 07/2005; 35(6):310-5. · 1.90 Impact Factor
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    ABSTRACT: Docetaxel and trastuzumab can be considered to be active drugs for HER 2-overexpressing metastatic breast cancer (MBC). This study was conducted to determine the activity of combination therapy with docetaxel and trastuzumab in MBC patients (pts) by assessing the response rate (RR), time to progression (TTP) and safety. We administered the combination of docetaxel 70 mg/m2 every 3 weeks and trastuzumab using a 4 mg/kg loading dose and thereafter 2 mg/kg weekly. One cycle was three weeks. Between March 2002 and May 2003, 40 pts with HER 2-positive (3+by immunohistochemistry 39, FISH+1) MBC were enrolled in this study, and 39 pts proved eligible. The overall RR was 72% (28/39) [95%CI 55.1%-85.0%], with 6 CR, 22 PR, 7 SD, 1 PD and 3 NE. The median follow-up time was 14.3 months, while the TTP was 6.5 months (range, 0.6-19.8), median OS has not yet been reached. The number of pts assessable for safety was 40. Hematological Grade 3-4 toxicities were leukopenia 87.5% (35/40) and neutropenia 82.5% (33/40). Non-hematological Grade 3 toxicities were weight gain in 2 pts, and anorexia, neuropathy, fever and rash in one pt each. The combination of docetaxel and trastuzumab was a well-tolerated and very active regimen for the treatment of pts with HER 2-overexpressing MBC.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2005; 32(3):335-9.
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    ABSTRACT: We studied the usefulness of the oral 5-FU anti-cancer drug 1-hexylcarbamoyl-5-fluorouracil (HCFU) + cyclophosphamide (CPM) + tamoxifen (TAM) (HCT group) in comparison with CMF + TAM (CMFT group) in adjuvant therapy for breast cancer by a non-inferiority study based on a multi-institutional joint study. Clinical stage I, II primary breast cancers with histologically positive axillary lymph node metastasis were randomly assigned to the HCT group or the CMFT group after primary surgery. We registered 136 cases (HCT group 68 cases, CMFT group 68 cases). No significant difference in the 5-year overall survival rate (OS) and the 5-year disease-free survival rate (DFS) was found between the two groups. In the stratified analysis, DFS in cases in which the number of metastatic lymph nodes was 1-3 was significantly better in the HCT group (HCT group 84.3%, CMFT group 69.4%, log-rank test p=0.0496). No significant difference in the total incidence of adverse effects was found between the two groups, but there were significantly less adverse effects of grade 2 or over in the HCT group (p=0.034). The QOL survey at 3 months after surgery showed a significant decline of the QOL regarding lassitude, degree of difficulty in daily life, satisfaction with treatment and present mood in the CMFT group. Study results suggest that 2-year HCT therapy including the oral 5-FU anti-cancer drug HCFU is a useful adjuvant therapy which can replace CMFT therapy in early breast cancer cases with 3 or lower metastatic lymph nodes.
    Oncology Reports 11/2004; 12(4):797-803. · 2.30 Impact Factor
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    ABSTRACT: A late phase II clinical study of S-1 against advanced or refractory breast cancer was done by 37 institutes in Japan. S-1 was administered twice daily at 80, 100 or 120 mg/body/day consecutively for 28 days followed by 14 days of rest (1 course). Eighty-three patients were enrolled and 81 were eligible for the study. The response ratio was 42.0% with 6 CR and 28 PR and its 95% confidence interval for the response was 31.1 to 53.5%. The median survival period was 910 days (95% confidence interval was 493-1, 083 days). The observed major adverse reactions (> or = grade 2) were as follows: hematological toxicities: leukopenia 21.0% (17/81), neutropenia 28.4% (23/81), erythropenia 4.9% (4/81); gastrointestinal toxicities: anorexia 9.9% (8/81), nausea and vomiting 12.3% (10/81), diarrhea 8.6% (7/81), stomatitis 1.2% (1/81), and fatigue 8.6% (7/81). The severe adverse reactions (> or = grade 3) were as follows; hematological toxicities: neutropenia 8.6% (7/81), anorexia 4.9% (4/81), fatigue 3.7% (3/81), nausea and vomiting 1.2% (1/81), diarrhea 1.2% (1/81), stomatitis 1.2% (1/81). Grade 4 adverse reactions (neutropenia and fatigue) were observed only in 1 patient. The ratio without hospitalization was 87.7%. These results strongly suggest the superior efficacy and safety of S-1 against patients suffering from advanced, refractory breast cancer. Therefore, S-1 may be a new therapeutic agent to prolong the survival period of breast cancer patients due to its high antitumor activity and low toxicity.
    Gan to kagaku ryoho. Cancer & chemotherapy 05/2004; 31(4):539-47.
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    ABSTRACT: S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoropyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer. A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n=111) were enrolled, and 108 patients were regarded as eligible. S-1 was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times. Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CR+PR) of 41.7% (95% confidence interval: CI, 32.3-51.5%). The incidences of toxicity (> or =grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group. S-1 was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.
    Breast Cancer 01/2004; 11(2):194-202. · 1.33 Impact Factor
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    ABSTRACT: Mutation of the class I beta-tubulin gene has been reported to be one of the mechanisms that cause resistance to paclitaxel. To assess the relationship between paclitaxel-resistance and class I beta-tubulin gene mutation in breast cancer, Japanese patients with breast cancer were screened for the class I beta-tubulin gene mutation. Total RNA was isolated from 82 breast cancer specimens and the corresponding normal tissues. Twenty-four of the 82 patients were treated with paclitaxel preoperatively and 12 of them did not respond to the treatment. Of the 82 breast cancer patients, 15 (18.3%) had silent polymorphism in exon 4, Leu217Leu (CTG/CTA). However, no mutations showing amino acid substitution of the beta-tubulin gene were detected in any of the patients, including 12 patients who did not respond to paclitaxel. Class I beta-tubulin gene mutation with amino acid substitution was not detected in 82 breast cancer specimens. Our results suggest that mutation of the class I beta-tubulin gene is unlikely to play an important role in the mechanism of resistance to paclitaxel in breast cancer.
    Cancer Letters 08/2003; 198(1):89-97. · 5.02 Impact Factor
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    ABSTRACT: A rare case of tuberculosis of axillary lymph nodes occurring with primary breast cancer is presented. A 78-year-old woman with no history of pulmonary tuberculosis was admitted to our hospital to undergo examination for a lump in her right breast. The tumor was in the upper outer quadrant of the right breast. On palpation, the tumor was 1.2 cm in diameter and axillary lymph node swelling was noted. Mammography disclosed a spiculated mass and swelling and calcification of the axillary lymph nodes. Sonography showed an irregular hypoechoic mass in the right breast and lymph node swelling in the right axilla, indicating breast cancer with axillary lymph nodes metastases. Chest X-ray showed clustered calcifications in the right axilla and a granular shadow in the right upper lobe. Breast conserving therapy was carried out. Invasive papillotubular carcinoma of the right breast and granulomas with calcification of lymph nodes, compatible with tuberculosis, was diagnosed. Tubercle bacillis were detected by culture of lymph nodes. This case suggests that X-ray is useful for diagnosing lymph node tuberculosis. Lymph node tuberculosis should be suspected when lymph node swelling is noted and X-ray shows clustered calcifications in axillary lymph nodes.
    Breast Cancer 02/2003; 10(2):175-8. · 1.33 Impact Factor

Publication Stats

245 Citations
49.71 Total Impact Points

Institutions

  • 2009–2012
    • Gunma Prefectural Cancer Center
      Maebashi, Gunma Prefecture, Japan
  • 2008
    • Saitama Cancer Center
      Saitama, Saitama, Japan
  • 2006
    • Niigata Cancer Center Hospital
      Niahi-niigata, Niigata, Japan