Publications by authors named "Morihiko Kimura"

35 Publications

[Follicle-Stimulating Hormone and Estradiol Levels in Japanese Women Treated with Toremifene and Anastrozole for Two Years - A Retrospective Analysis of Data from a Prospective Randomized Trial].

Gan To Kagaku Ryoho 2018 Dec;45(12):1725-1728

Multi-Hormone Study Group (Dept. of Breast and Thyroid Surgery, Kitakyushu Municipal Medical Center).

The criteria for biological postmenopause have not been clearly defined, although determining the menopausal status is crucial for selecting agents for adjuvant endocrine therapy for patients with breast cancer. The long-term effects of adjuvant toremifene(TOR)and anastrozole(ANA)on serum follicle-stimulating hormone(FSH)and estradiol(E2)levels in Japanese women were examined using data from a prospective randomized study that mainly studied serum lipids and bone metabolism for 2 years. The study medications were administered orally daily at 40 mg and 1 mg for TOR and ANA, respectively. Sixty-nine patients were randomly assigned to the TOR group(n=36)or ANA group(n=33). FSH and E2 levels were measured using chemiluminescent immunoassay. The mean ages of the patients in the TOR and ANA groups were 62.5 and 60.0 years, respectively. None of the patients experienced menstruation during the course of the study. The baseline serum FSH level in the TOR group(69.6mIU/mL)decreased to 59.2%, 54.6%, and 50.0% at 6, 12, and 24 months, respectively, after therapy commencement. The FSH levels ranged from 8.6 to 68.1mIU/mL and were<20mIU/mL in 2 patients(9.5%; 8.6 and 14.4mIU/mL). The serum FSH levels in the ANA group did not change markedly over 24months. The baseline serum E2 level in the ANA group(11.6 pg/mL)decreased to 72.4%, 70.7%, and 61.2%at 6, 12, and 24months, respectively, after therapy commencement. The serum E2 level in the TOR group did not change markedly over 24 months. When switching to other endocrine agents as adjuvant therapy for patients with breast cancer treated with TOR, the serum FSH level decreased to half of the preinitiation level, and one-tenth of the FSH levels was<20mIU/mL, while the postmenopausal serum E2 level was maintained.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2018

Higher efficacy and complete response with administration of eribulin for recurrent squamous cell breast carcinoma: A case report.

Mol Clin Oncol 2018 Sep 19;9(3):318-320. Epub 2018 Jul 19.

Department of Breast Surgery, Ota Memorial Hospital, Otashi, Gunma 373-8585, Japan.

Squamous cell carcinoma is a rare histological type of breast cancer classified as metaplastic carcinoma. Metaplastic carcinoma involves differentiation of the breast glandular duct cells into mesenchymal tissues. While the chemotherapy regimen for metaplastic carcinoma is often similar to that for invasive ductal carcinoma, recurrence is associated with a poor prognosis due to the inadequate therapeutic efficacy of the regimen. We herein present the case of a 42-year-old female patient who underwent mastectomy of the right breast and right axillary node lymphadenectomy for T4N3aM0 breast cancer stage. The cancer was histopathologically diagnosed as squamous cell carcinoma of the breast. Adjuvant cyclophosphamide-epirubicin-fluorouracil (CEF) postoperative chemotherapy was administered, and lymphadenectomy of right-sided parasternal lymphatic metastases with pleural drainage was subsequently performed. Radiotherapy was administered to the thoracic wall and supraclavicular lymph nodes at 60 Gy. Positron emission tomography (PET)-computed tomography (CT) examination 3 months after the radiotherapy identified accumulation of fluorodeoxyglucose (FDG) in a supraclavicular lymph node and the thoracic wall; hence, a chemotherapeutic regimen with eribulin was initiated. At 11 months after initiation of eribulin, complete response was achieved, indicated by the absence of FDG accumulation in both the supraclavicular lymph node and the thoracic wall on PET-CT. The treatment efficacy of eribulin is considered to be a result of the mixed morphology of squamous cell carcinoma, including the presence of an epithelial component, such as adenocarcinoma cells, and a mesenchymal component, in the form of sarcomatoid cells. Eribulin displayed an effect similar to that of adriamycin against malignant soft tissue tumors and was shown to effectively target mesenchymal components. In cases of reduced expression of the DNA repair pathway components, such as in metaplastic carcinomas, eribulin may be more effective compared with adriamycin, the mechanism of action of which involves inhibition of DNA synthesis. A superior therapeutic effect was obtained with eribulin in squamous cell carcinoma. Therefore, eribulin appears to be a promising, effective therapeutic choice for the management of metaplastic carcinomas, including squamous cell carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2018.1676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109669PMC
September 2018

Phase II Study of S-1 plus Trastuzumab for HER2-positive Metastatic Breast Cancer (GBCCSG-01).

Anticancer Res 2018 02;38(2):905-909

Breast Surgery, Ota Memorial Hospital, Gunma, Japan.

Aim: Treatment strategies for patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) have significantly progressed. The use of trastuzumab, a monoclonal antibody targeting the HER2 (human epidermal growth factor 2) protein, in combination with chemotherapy improves survival in patients with HER2-positive breast cancer. S-1, an oral combination of fluorouracil derivatives, is widely used in Japan and is more convenient than intravenous drugs. However, little is known about the combination of S-1 and trastuzumab in patients with HER2-positive MBC.

Patients And Methods: We conducted a single-arm, open-label, multicenter prospective phase II study to evaluate the efficacy of an S-1 plus trastuzumab regimen for HER2-positive MBC. S-1 was administered orally [80-120 mg, based on body surface area (BSA)] twice a day for 14 consecutive days in a 3-week cycle. Patients with BSA of <1.25 m received a total of 80 mg of S-1, those with BSA ≥1.5 m received 120 mg, and the remaining received 100 mg daily in two divided doses. Trastuzumab was administered intravenously at 8 mg/kg on day 1 of the first cycle and at 6 mg/kg on day 1 of subsequent cycles, i.e., every 3 weeks.

Results: Between December 2008 and March 2013, 10 patients were enrolled and received a median of 17 (range=3-76) cycles of treatment. Overall response and clinical benefit rates were 60.0% and 90.0%, respectively. Progression-free survival was 15.8 (95% confidence interval=9.4-29.6) months and overall survival was 45.5 (95% confidence interval=37.1-62.2) months. Grade 3/4 adverse events included were neutropenia and hyperglycemia in one patient each (10.0%). There was no clinically significant cardiotoxicity.

Conclusion: The combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this study. S-1 plus anti-HER2 therapy is a feasible treatment option for HER2-positive MBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.12301DOI Listing
February 2018

Serum lipid and bone metabolism effects of Toremifene vs. Letrozole as adjuvant therapy for postmenopausal early breast cancer patients: results of a multicenter open randomized study.

Cancer Chemother Pharmacol 2018 02 1;81(2):269-275. Epub 2017 Dec 1.

Teikyo University School of Medicine, Tokyo, Japan.

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1-2, node metastases (n = 0-3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-017-3491-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778152PMC
February 2018

[A Case of Recurrent Breast Cancer with Carcinomatous Pleurisy Successfully Treated with Biweekly Paclitaxel and Bevacizumab].

Gan To Kagaku Ryoho 2016 Nov;43(11):1397-1400

Dept. of Breast Surgery, Ota Memorial Hospital.

A 72-year-old woman underwent mastectomy with axillary lymph node dissection for left breast cancer at the age of 43 years, and was diagnosed with breast cancer metastasis to the pleura at the age of 68 years. She had been sequentially treated with hormonal therapies, but complained of a cough and dyspnea after 4 years. Chest radiography showed right pleural effusion, and cytological examination of the pleural effusion revealed adenocarcinoma cells. Biweekly paclitaxel and bevacizumab therapy was administered. Two months later, the pleural effusion had disappeared. Biweekly paclitaxel and bevacizumab therapy was continued without any severe adverse events. After 30 months, the patient has remained free of carcinomatous pleurisy recurrence. Therefore, biweekly paclitaxel and bevacizumab therapy can be safely and effectively administered to elderly patients with carcinomatous pleurisy.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2016

[An Elderly Patient with Metastatic Breast Cancer Who Developed Severe Adverse Events such as Stomatitis and Interstitial Pneumonia after Everolimus plus Exemestane Treatment].

Gan To Kagaku Ryoho 2016 Jun;43(6):753-5

Dept. of Breast Surgery, Ota Memorial Hospital.

An 80-year-old woman was diagnosed with right breast cancer with clinical Stage IIIA 6 years previously. She underwent mastectomy and axillary lymph node dissection. The pathological diagnosis was invasive micropapillary carcinoma with lymph node involvement. Immunohistochemically, the tumor was positive for estrogen receptor and progesterone receptor, and negative for HER2. Postoperatively, the patient was treated with adjuvant chemotherapy consisting of cyclophosphamide, epirubicin, 5-fluorouracil, and paclitaxel, followed by endocrine therapy with letrozole. Four years after surgery, she experienced a recurrence of breast cancer in the thoracic wall, and was treated with exemestane, toremifene, and fulvestrant for 1 year and 5 months. However, she developed carcinomatous pleurisy and was treated with eribulin. This last treatment was ineffective. Subsequently, she received combination therapy with everolimus and exemestane. Although the pleural effusion reduced markedly after 5 weeks, stomatitis, diarrhea, melena, and interstitial pneumonia occurred as adverse events. The symptoms improved after drug discontinuation and steroid therapy. The combination therapy with everolimus and exemestane is a prospective therapy for hormone-resistant recurrent breast cancer, but the management of adverse events is very important.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2016

Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer.

Breast Cancer 2014 May 12;21(3):275-83. Epub 2012 Sep 12.

Department of Surgery, Gunma Cancer Center, Ota, Japan,

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12282-012-0394-6DOI Listing
May 2014

Women prefer adjuvant endocrine therapy to chemotherapy for breast cancer treatment.

Breast Cancer 2013 Jan 23;20(1):67-74. Epub 2011 Nov 23.

Department of Breast and Endocrine Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

Background: We attempted to determine the preferences of women regarding the benefits they considered necessary to make adjuvant therapy worthwhile, and to compare preferences for adjuvant endocrine therapy, chemotherapy, and trastuzumab therapy. We also investigated the effect of information about cost on women's treatment preferences.

Patients And Methods: Consecutive women who had a medical examination at the Breast Clinic, Ota General Hospital, were included in our study. We collected a questionnaire from a total of 365 women; 297 completed responses were included in the study.

Results: Among 297 women, 105 had breast cancer that had been treated and 192 did not have breast cancer; 38% of women judged that a 5% or less gain in the probability of survival was sufficient to make endocrine therapy worthwhile; 28% of participants judged that chemotherapy was worthwhile; 24% of participants judged that trastuzumab therapy was worthwhile. Women indicated that they were more likely to receive adjuvant endocrine therapy than chemotherapy or trastuzumab therapy, for the same gains in the probability of survival. Cost information about treatments did not affect women's treatment preferences. Younger women tended to judge improvements in survival sufficient to make adjuvant endocrine and chemotherapy worthwhile, as compared to older women. The comparisons were statistically significant in the 10 and 20% categories for endocrine therapy and chemotherapy.

Conclusion: Women prefer endocrine therapy to chemotherapy or trastuzumab therapy, given the same projected treatment benefits. Younger women prefer both chemotherapy and endocrine therapy as compared with older woman.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12282-011-0310-5DOI Listing
January 2013

Effects of toremifene and anastrozole on serum lipids and bone metabolism in postmenopausal females with estrogen receptor-positive breast cancer: the results of a 2-year multicenter open randomized study.

Breast Cancer Res Treat 2011 Aug 3;128(3):775-81. Epub 2011 Jun 3.

Department of Surgery, Kitakyushu Municipal Medical Center, Fukuoka, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-011-1608-xDOI Listing
August 2011

Breast conserving surgery for male noninvasive intracystic papillary carcinoma: a case report.

Tokai J Exp Clin Med 2010 Apr 20;35(1):13-6. Epub 2010 Apr 20.

Department of Surgery, Sougo Oota Hospital, 29-5 Hachimancho, Oota, Gunma 378-0028, Japan.

We report an exceedingly rare case of male breast cancer on two brothers. The patient has family history that his younger brother had breast cancer 5 years ago. The patient was 70-years old man who presented with chief complaint of an indolent tumor mass of the left breast. Mammography demonstrated a well defined mass with microcalcifications. Noninvasive intracystic papillary carcinoma was diagnosed by excisional biopsy. We performed breast conserving surgery (BCS) with sentinel lymph node biopsy for this patient. The histological diagnosis was same as above, with no metastasis of sentinel lymph node. Immunohistochemical study showed estrogen receptor (ER) and progesterone receptor (PgR) were positive respectively, and human epidermal growth factor receptor type 2 (HER2/c-erbB-2) was negative. After surgery, he underwent radiation therapy of 60 Gy for left chest wall include nipple and areolar area. We report the case of BCS for male breast cancer. The preservation of the nipple areolar complex in male patients may also have a positive psychological impact as is the case in women treated for breast cancer. Our patients report an outstanding cosmetic result. As for the man, breast conserving therapy should be enforced without overt nipple and areolar involvement like a woman.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2010

Effects of toremifene and tamoxifen on lipid profiles in post-menopausal patients with early breast cancer: interim results from a Japanese phase III trial.

Jpn J Clin Oncol 2010 Jul 8;40(7):627-33. Epub 2010 Apr 8.

Breast Cancer Center, Toyosu Hospital, Showa University, Tokyo, Japan.

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyq021DOI Listing
July 2010

Phase II study of 4-weekly capecitabine monotherapy in advanced/metastatic breast cancer.

Breast Cancer 2010 Oct 25;17(4):233-40. Epub 2009 Jul 25.

Tokyo Medical University, Shinjuku-ku, Japan.

Background: 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.

Methods: 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).

Results: 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%).

Conclusions: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12282-009-0137-5DOI Listing
October 2010

Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan.

Breast Cancer 2010 Jul 3;17(3):190-8. Epub 2009 Jul 3.

Department of Surgery, Gunma Prefectural Cancer Center, Ota, Japan.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12282-009-0132-xDOI Listing
July 2010

[Efficacy of treatment with high-dose toremifene in patients with metastatic breast cancer resistant to aromatase inhibitor treatment].

Gan To Kagaku Ryoho 2009 Jun;36(6):1013-6

Dept. of Surgery, Sougo Oota Hospital, Japan.

The efficacy of aromatase inhibitors(AI)has been established for adjuvant and metastatic breast cancer. However, decision making regarding treatment becomes difficult after AI treatment. Recently, high-dose toremifene(HD-TOR, TOR 120 mg daily)showed efficacy in these patients. We attempted to study retrospectively the efficacy and safety of HD-TOR treatment. Seven patients received HD-TOR. The overall response rate was 29%(PR 2)and clinical benefit (CR, PR, long SD)was 57%(PR 2, long SD 7). HD-TOR may be an optional treatment for MBC after AI treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2009

Efficacy of doxifluridine combined with weekly paclitaxel therapy in the treatment of advanced or recurrent breast cancer: results of the JMTO BC01 phase II trial.

Anticancer Drugs 2008 Oct;19(9):911-5

Kumamoto City Hospital, Kumamoto City, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CAD.0b013e3283099e71DOI Listing
October 2008

Neoadjuvant paclitaxel for operable breast cancer: multicenter phase II trial with clinical outcomes.

Anticancer Res 2008 Mar-Apr;28(2B):1239-44

Department of Surgery, General Ota Hospital, Ota, Gunma 373-8585, Japan.

Aim: To determine the efficacy of preoperative weekly paclitaxel for patients with operable breast cancer tumors greater than 3 cm.

Patients And Methods: 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.

Results: 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.

Conclusion: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2008

Relationship between the signal ratios of HER-2/CEP17 and c-MYC/CEP17 and the pathological response of neoadjuvant therapy using docetaxel and trastuzumab in breast cancer.

Mol Med Rep 2008 Jan-Feb;1(1):71-5

Department of Pathology, Saitama Cancer Center, Saitama 362-0806, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2012

Study of time-course changes in annual recurrence rates for breast cancer: data analysis of 2,209 patients for 10 years post-surgery.

Breast Cancer Res Treat 2007 Dec 1;106(3):407-11. Epub 2007 Feb 1.

Department of Surgery, General Ota Hospital, 29-5, Ota-shi, Gunma, 373-8585, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-007-9510-2DOI Listing
December 2007

[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].

Gan To Kagaku Ryoho 2006 Oct;33(10):1411-5

Dept. of Surgery, Niigata Cancer Center Hospital.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2006

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

Breast Cancer 2006 ;13(2):166-71

Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2325/jbcs.13.166DOI Listing
August 2006

Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel.

Clin Cancer Res 2005 Dec;11(24 Pt 1):8837-44

Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, and Department of Surgery, Niigata Cancer Center Hospital, Japan.

Purpose: 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.

Experimental Design: 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.

Results: 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).

Conclusions: The results of the present study suggested that YB-1 may be involved in the development of resistance to paclitaxel in breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-05-0945DOI Listing
December 2005

Toremifene: an evaluation of its safety profile.

Breast 2006 Apr 9;15(2):142-57. Epub 2005 Nov 9.

Division of Hematology/Oncology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.

Toremifene has been in clinical use for 8 years for the treatment of advanced hormone-sensitive breast cancer and the adjuvant treatment of early breast cancer. More than 350,000 patient treatment years have accumulated, sufficient to allow evaluation of its longer-term safety profile in comparison with tamoxifen and, where possible, with raloxifene and aromatase inhibitors. We reviewed all preclinical and clinical safety data from 1978 to 2004 and comparative clinical safety data between October 1995 and the end of 2004. Secondary endometrial cancer incidence was lower with toremifene than with tamoxifen and was similar to that with raloxifene. It is speculated that toremifene may unmask existing endometrial tumors rather than induce new events. The risk of stroke, pulmonary embolism, and cataract may be lower with toremifene than with tamoxifen and the risk of pulmonary embolism and deep vein thrombosis lower than with raloxifene. Beneficial estrogen agonistic effects were equivalent to those of tamoxifen regarding bone mineral density and superior regarding lipid profiles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.breast.2005.09.007DOI Listing
April 2006

[Late phase II clinical study of KW-2307 in advanced/recurrent breast cancer patients (II)].

Gan To Kagaku Ryoho 2005 Jul;32(7):983-90

Dept. of Surgery, Tokyo Metropolitan Komagome Hospital.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2005

Late phase II clinical study of vinorelbine monotherapy in advanced or recurrent breast cancer previously treated with anthracyclines and taxanes.

Jpn J Clin Oncol 2005 Jun 1;35(6):310-5. Epub 2005 Jun 1.

Department of Clinical Trials and Research, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8687 Japan.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyi090DOI Listing
June 2005

[Study of three-weekly docetaxel and weekly trastuzumab treatment in HER 2-overexpressing metastatic breast cancer patients].

Gan To Kagaku Ryoho 2005 Mar;32(3):335-9

Japan East Cancer Breast Cancer Consortium.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2005

A phase II study of S-1 in patients with metastatic breast cancer--a Japanese trial by the S-1 Cooperative Study Group, Breast Cancer Working Group.

Breast Cancer 2004 ;11(2):194-202

Department of Clinical Research and Surgery, National Shikoku Cancer Center Hospital, Horinouchi 13, Matsuyama 790-0007, Japan.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF02968301DOI Listing
December 2004

1-hexylcarbamoyl-5-fluorouracil + cyclophosphamide + tamoxifen versus CMF + tamoxifen in women with lymph node-positive breast cancer after primary surgery: a randomized controlled trial.

Oncol Rep 2004 Oct;12(4):797-803

Breast Cancer Center, Toyosu Hospital, Showa University School of Medicine, Tokyo 135-8577, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2004

Combination chemotherapy with docetaxel and doxifluridine showed a beneficial outcome in advanced or recurrent breast cancer patients with longer disease-free interval.

Anticancer Res 2004 May-Jun;24(3b):2085-91

Department of Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto 862-8505, Japan.

Unlabelled: Fundamental studies have confirmed that combination chemotherapy with docetaxel and doxifluridine (a capecitabine metabolite) is very useful in the treatment of breast cancer. This study investigated the usefulness and tolerability of a combination chemotherapy consisting of docetaxel administration on day 8 of doxifluridine therapy in 40 advanced/recurrent breast cancer patients. The overall response rate was 41.0% in 39 eligible patients. The median time to progression (TTP) for all patients was 295 days. Many responders had lung metastasis, soft tissue metastasis or a good performance status, whereas the clinical response showed no correlations with the estrogen receptor status or prior treatment with an anthracycline. The most common hematological toxicities were leukopenia and neutropenia, but dose reduction or delay of administration of either drug was unnecessary.

Conclusion: The good response rate and long TTP of this doxifluridine plus docetaxel regimen indicate its potential as a first- or second-line treatment for advanced/recurrent breast cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2004

[A late phase II clinical study of S-1 in patients with progressed, refractory breast cancer].

Gan To Kagaku Ryoho 2004 Apr;31(4):539-47

Dept. of Clinical Research & Surgery, National Shikoku Cancer Center Hospital.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2004

Mutation of the class I beta-tubulin gene does not predict response to paclitaxel for breast cancer.

Cancer Lett 2003 Jul;198(1):89-97

Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0304-3835(03)00279-9DOI Listing
July 2003
-->