s-1-(combination) and Breast-Neoplasms

In Japan, the history of postoperative chemotherapy for breast cancer started with 5-fluorouracil (5-FU), launched in the 1980s. Currently, oral fluoropyrimidine-based regimens indicated for the treatment of breast cancer in Japan include tegafur plus uracil (UFT); tegafur, gimeracil, and oteracil (TS-1); doxifluridine; and capecitabine. In particular, UFT represents an important option for long-term treatment because of minimal adverse events and the potential for long-term maintenance of effective plasma concentrations of 5-FU to inhibit micrometastasis after surgery. Therefore, various clinical studies of postoperative adjuvant chemotherapy with UFT have been conducted in patients with completely resected tumors. Recent studies have shown that UFT prolongs survival after tumor resection in patients with gastric cancer, colorectal cancer, and lung cancer. In patients with breast cancer, large clinical trials of UFT-based postoperative chemotherapy conducted in Japan have shown that UFT is useful for the treatment of intermediate-risk patients with no lymph node metastasis. This paper reviews the results of clinical studies of UFT conducted in Japan to assess the therapeutic usefulness of this oral 5-FU. The types of patients most likely to benefit from UFT are discussed on the basis of currently available evidence and a global consensus of treatment recommendations. The optimal timing of endocrine therapy and strategies for postoperative adjuvant chemotherapy with UFT in patients with breast cancer are also discussed.

Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Female; Floxuridine; Fluorouracil; Humans; Japan; Methotrexate; Oxonic Acid; Tegafur; Uracil

Cytotoxic agents such as anthracycline or taxanes have provided a good clinical response for breast cancer patients, although they have failed to prolong the survival rate and to improve the quality of life (QOL) of these patients. On the other hand, cytostatic agents such as 5-fluorouracil (5-FU) have to be focused to accommodate a long term progression with respect to efficacy and the patients' QOL improvement. S-1 was a newly developed and orally administered fluorinated pyrimidine containing 1 M tegafur (FT) and two classes of a modulator, 5-chloro-2,4-dihydroxypyrimidine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT : CDHP : Oxo= 1 : 0.4 : 1. Specific dose limiting factors such as neutropenia, diarrhea and stomatitis have been observed in a previous phase I study. Two phase II studies of 4 weeks treatment of S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) for the advanced or metastatic breast cancer patients were carried out in Japan. Among 108 evaluable patients for response, there were 10 complete response (CR) and 35 partial response (PR) with an overall response rate of 41.7% (95% confidence interval, 32.3-51.5%). The incidence of toxicity (> or = grade 3) was as followed: neutropenia 9.3%, anemia 0.9%, stomatitis 1.9% and nausea/vomiting 0.9%. The median follow-up period for patients was 802 days. S-1 will be the new promising oral agent like a capecitabine which has been widely used as a third-line chemotherapy for the heavily treated breast cancer patients.

Topics: Administration, Oral; Anemia; Antimetabolites, Antineoplastic; Breast Neoplasms; Carcinoma, Ductal, Breast; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Mastectomy, Segmental; Nausea; Neutropenia; Oxonic Acid; Quality of Life; Stomatitis; Survival Rate; Tegafur

Topics: Animals; Antimetabolites, Antineoplastic; Breast Neoplasms; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Combinations; Female; Humans; Oxonic Acid; Pyridines; Tegafur

After nearly four decades of clinical experience with the fluoropyrimidines, 5-fluorouracil (5-FU) remains an integral part of chemotherapy for colorectal cancer. A range of 5-FU treatment regimens with or without biochemical modulation are currently used and toxicity appears to be schedule dependent. The use of oral 5-FU was abandoned because of erratic absorption caused by varying levels of dihydropyrimidine dehydrogenase (DPD) found in the gastrointestinal tract. This effect may be overcome by administering agents that are converted to 5-FU or by inhibiting or inactivating DPD. Xeloda((R)) (capecitabine) was designed as an orally administered, selectively tumoractivated(TM) cytotoxic agent which achieves higher levels of 5-FU in the primary tumor than in plasma or other tissues. The United States Food and Drug Administration (FDA) has approved Xeloda for use in patients with metastatic breast cancer resistant to paclitaxel and in whom further anthracycline therapy is contraindicated. Xeloda is also registered in Canada, Switzerland, Thailand and Argentina. In phase II clinical trials in colorectal cancer, Xeloda produced response rates of 21-24% and median time to disease progression of 127-230 days. Other oral agents in development for the treatment of colorectal cancer include tegafur/uracil plus oral leucovorin, S-1 and eniluracil plus oral 5-FU.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Combinations; Fluorouracil; Humans; Leucovorin; Oxonic Acid; Pyridines; Tegafur; Uracil

We have previously demonstrated S-1 is non-inferior to taxane with respect to overall survival as first-line chemotherapy for HER2-negative metastatic breast cancer. We aimed to confirm whether S-1 is also non-inferior to anthracycline-containing regimens in the same setting.. We conducted an open-label, non-inferiority, Phase 3 study. Individuals who had HER2-negative metastatic breast cancer, had received no chemotherapy for advanced disease and had endocrine therapy resistance, were randomly assigned to the anthracycline-containing regimens or S-1. The primary endpoint was overall survival. A pre-planned combined analysis of our two Phase 3 studies was also carried out.. We enrolled 230 patients (anthracycline, n = 115; S-1, n = 115). Median overall survival was 30.1 months (95% CI 24.9-35.8) with the S-1 group and 33.7 months (95% CI 25.5-36.9) with the anthracycline group. The HR for the anthracycline group was 1.09 (95% CI 0.80-1.48). The combined analysis constituted 814 patients (395 assigned to standard treatment (anthracycline or taxane); 419 assigned to S-1). Median overall survival was 36.3 months in the standard treatment group and 32.7 months in the S-1 group. S-1 was non-inferior to standard treatment in terms of overall survival (HR 1.06 (95% CI 0.90-1.25); P non-inferiority = 0.0062).. S-1 could be considered a new treatment option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer.. The University Hospital Medical Information Network, Japan: UMIN000005449. This trial was registered on 15 April, 2011.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents, Hormonal; Breast Neoplasms; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Receptor, ErbB-2; Survival Analysis; Taxoids; Tegafur; Treatment Outcome; Young Adult

Oral fluoropyrimidines, such as S-1, have been shown to have a role in controlling disease progression in metastatic breast cancer. We examined adjuvant treatment with S-1 in patients with oestrogen receptor (ER)-positive and HER2-negative primary breast cancer.. We did a multicentre, open-label, randomised, controlled, phase 3 trial in 139 sites (137 hospitals and two clinics). Eligible patients were women aged 20-75 years with histologically diagnosed stage I to IIIB invasive breast cancer (intermediate to high risk of recurrence). Patients were temporarily registered at participating institutions and biopsy or surgical samples were collected and sent for central pathological assessment. Patients received 5 years of standard adjuvant endocrine therapy (selective oestrogen receptor modulators with or without ovarian suppression and aromatase inhibitors) with or without 1 year of S-1. Oral S-1 80-120 mg/day was administered twice a day for 14 days with 7 days off. Randomisation (1:1) using the minimisation method was done with six stratification factors (age, axillary lymph node metastasis at surgery or sentinel lymph node biopsy, preoperative or postoperative (neoadjuvant or adjuvant) chemotherapy, preoperative endocrine therapy, proportion of ER-positive cells, and study site). The primary endpoint was invasive disease-free survival, in the full analysis set (all randomly assigned patients, excluding those with significant protocol deviations). The safety analysis set consisted of all patients who received at least one dose of study treatment. Here, we report the results from the interim analysis at the data cutoff date Jan 31, 2019. This trial is registered with Japan Registry of Clinical Trials, jRCTs051180057, and the University hospital Medical Information Network, UMIN000003969.. Between Feb 1, 2012, and Feb 1, 2016, 1930 patients were enrolled in the full analysis set, 957 (50%) received endocrine therapy plus S-1 and 973 (50%) received endocrine therapy alone. Median follow-up was 52·2 months (IQR 42·1-58·9). 155 (16%) patients in the endocrine therapy alone group and in 101 (11%) patients in the endocrine therapy plus S-1 group had invasive disease-free survival events (hazard ratio 0·63, 95% CI 0·49-0·81, p=0·0003). As the primary endpoint was met at interim analysis, the trial was terminated early. The most common grade 3 or worse adverse events were decreased neutrophil count (72 [8%] of 954 patients in the endocrine therapy plus S-1 group vs seven [1%] of 970 patients in the endocrine therapy alone group), diarrhoea (18 [2%] vs none), decreased white blood cells (15 [2%] vs two [<1%]), and fatigue (six [<1%] vs none). Serious adverse events were reported in nine (1%) of 970 patients in the endocrine therapy alone group and 25 (3%) of 954 patients in the endocrine therapy plus S-1 group. There was one (<1%) possible treatment-related death in the endocrine therapy plus S-1 group due to suspected pulmonary artery thrombosis.. These data suggest that this combination of S-1 with endocrine therapy could be a potential treatment option for this intermediate and high-risk group of patients with ER-positive, HER2-negative primary breast cancer.. Public Health Research Foundation (Japan), Taiho Pharmaceutical.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Receptor, ErbB-2; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Tegafur; Time Factors; Young Adult

We investigated the quantification of the response shift-adjusted treatment effect on quality-of-life (QOL) data in a randomized controlled trial of taxane versus S-1 for patients with metastatic breast cancer (SELECT-BC).. This study was a secondary data analysis of a previously published trial. The response shift-adjusted treatment effect on health-related QOL (HRQOL) data measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was estimated using structural equation modeling techniques in addition to quantifying the "true" treatment effect. Measurement invariances in the values of the common factor loadings, intercepts, and residual variances between before treatment and at the 3-, 6-, and 12-month visits were considered the response shift effects.. In the taxane group, we observed positive recalibration effects for role functioning and positive reprioritization and negative recalibration effects for emotional functioning. The observed change of -4.56 for role functioning comprised +2.26 response shifts and -6.82 "true" change. The observed change of +9.41 for emotional functioning comprised +12.43 response shifts and -1.17 "true" change. In the S-1 group, we observed positive reprioritization and negative recalibration effects for emotional functioning and positive reprioritization effects for social functioning. The observed change of +10.54 for emotional functioning comprised +10.07 response shifts and +0.47 "true" change. The observed change of +2.43 for social functioning comprised +3.50 response shifts and -1.07 "true" change.. Detailed analysis of the response shift effects will improve the evaluation reliability of observed HRQOL data during clinical trials.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Drug Combinations; Female; Humans; Latent Class Analysis; Middle Aged; Oxonic Acid; Quality of Life; Reproducibility of Results; Surveys and Questionnaires; Taxoids; Tegafur

In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer.. The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed.. This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment.. Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1.. S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.

Topics: Ado-Trastuzumab Emtansine; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Humans; Maytansine; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Receptor, ErbB-2; Tegafur; Trastuzumab; Treatment Outcome

The aim of this study was to investigate the impact of adverse events (AEs) on health utility and health-related quality of life (HRQOL) in patients with metastatic breast cancer undergoing first-line chemotherapy.. We analyzed the data from the SELECT BC study, a multicenter, open-label, randomized, phase III study conducted in Japan, which compared first-line S-1 with taxane therapies. Heath utility and HRQOL were assessed using the EQ-5D-3L and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline and 3, 6, and 12 months after treatment initiation. Health utility was calculated based on societal preferences, and AEs were reported at each cycle of the study treatment. Linear marginal mean models were used to quantify the impact of the last AEs (with 10 or more incidences) observed before HRQOL assessment on health utility and HRQOL.. Analysis included 380 patients and 12 (of 15) AEs. Grade 1 nausea and oral mucositis, grade 1 and 2 edema, and grade 2 fatigue, motor and sensory neuropathy, and myalgia were significantly associated with disutility, measured using the EQ-5D-3L. Grade 1 oral mucositis, grade 1 and 2 fatigue, and grade 2 sensory neuropathy were significantly associated with impaired global health status in the EORTC QLQ-C30. AEs associated with decrements in the five functioning scales included fatigue, oral mucositis, nausea, edema, motor and sensory neuropathy, and myalgia.. We reported disutilities caused by AEs in patients with metastatic breast cancer under chemotherapy. These findings can be applied to future model-based cost-effectiveness analyses.. C000000416.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Drug Combinations; Female; Health Status; Humans; Japan; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Quality of Life; Surveys and Questionnaires; Taxoids; Tegafur; Time Factors

To evaluate the effects of S-1, an orally administered 5-FU agent, versus taxane on patient-reported outcomes (PROs) in the SELECT BC trial.. Patients with HER2-negative and endocrine treatment-resistant breast cancer with metastasis or recurrence after surgery were randomly assigned to receive first-line taxane or S-1. PROs (secondary endpoint) were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Patient Neurotoxicity Questionnaire (PNQ) at baseline and at 3, 6, and 12 months. We conducted a responder analysis for the QLQ-C30 and PNQ and created cumulative distribution function (CDF) plots as a sensitivity analysis.. The questionnaire response rates were over 80% from 386 patients, who completed at least one baseline questionnaire. S-1 was significantly superior to taxane with respect to 6 scales (physical functioning [p = 0.03], role functioning [p = 0.04], social functioning [p < 0.01], financial difficulties [p = 0.01], global health status [p = 0.02], and constipation [p < 0.01]) and sensory neuropathy (p = 0.01). The CDF plots partially supported the conclusions and their robustness.. First-line S-1 therapy has clinical benefits with respect to many aspects of health-related quality of life for metastatic breast cancer patients.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Drug Combinations; Female; Fluorouracil; Health Status; Humans; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Patient Reported Outcome Measures; Quality of Life; Surveys and Questionnaires; Taxoids; Tegafur

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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Prospective Studies; Receptor, ErbB-2; Tegafur; Trastuzumab

The goal of chemotherapy for metastatic breast cancer (MBC) is to prolong survival and maintain health-related quality of life. This study aimed to evaluate long-term health status of patients with MBC who participated in the phase III randomized SELECT BC trial.. In the SELECT BC trial, patients were randomly allocated to the S-1 or taxane (paclitaxel or docetaxel) arm. Health status was assessed by EQ-5D at pre-treatment, 3 and 6 months after randomization, and every 6 months thereafter to the extent possible. Least square mean scores were assessed to compare EQ-5D index values between groups. Time to deterioration analysis was also performed by defining the minimally important difference of EQ-5D as 0.05 or 0.1.. The number of patients for EQ-5D analysis was 175 and 208 in the taxane and S-1 arms, respectively. Least square mean EQ-5D index values up to 60 months were 0.741 (95 % CI [0.713-0.769]) in the taxane arm and 0.748 [0.722-0.775] in the S-1 arm. The EQ-5D index value during PFS up to 12 months in the S-1 was superior to the corresponding index value in the taxane (0.812 [0.789-0.834] vs. 0.772 [0.751-0.792], P = 0.009). Time to deterioration analysis also revealed that S-1 significantly delayed the deterioration of EQ-5D index value during the period before progression (P = 0.002 and 0.003).. Our findings suggest that the EQ-5D index value was higher in patients treated with S-1 during first-line chemotherapy. Considering non-inferiority of S-1 in terms of OS, obtained quality-adjusted life years may be greater in the S-1 arm.

Topics: Adult; Aged; Breast Neoplasms; Drug Combinations; Female; Health Status; Humans; Middle Aged; Oxonic Acid; Quality of Life; Quality-Adjusted Life Years; Surveys and Questionnaires; Taxoids; Tegafur

Oral fluoropyrimidines are used for the first-line treatment of metastatic breast cancer to avoid severe adverse effects, although firm supporting evidence is lacking. We aimed to establish whether S-1 is non-inferior to taxanes in this setting.. We did an open-label, non-inferiority, phase 3 trial at 154 hospitals in Japan. We enrolled individuals who had HER2-negative metastatic breast cancer who had received no chemotherapy for advanced disease, and who were resistant to endocrine treatment. Patients were randomly assigned (1:1) either to taxane (docetaxel 60-75 mg/m(2) at intervals of 3-4 weeks; paclitaxel 80-100 mg/m(2) weekly for 3 of 4 weeks; or paclitaxel 175 mg/m(2) at intervals of 3-4 weeks) or to S-1 (40-60 mg twice daily for 28 consecutive days, followed by a 14-day break). Randomisation was done centrally with the minimisation method, with stratification by institution, liver metastasis, oestrogen and progesterone receptor status, previous treatment with taxanes or oral fluorouracil, and time from surgery to recurrence. The primary endpoint was overall survival, with a prespecified non-inferiority margin of 1·333 for the hazard ratio (HR). The primary efficacy analysis was done in the full analysis set, which consisted of all patients who took at least one study treatment and who had all data after randomisation. This trial is registered with the University Hospital Medical Information Network, Japan (protocol ID C000000416).. Between Oct 27, 2006, and July 30, 2010, we enrolled 618 patients (309 assigned to taxane; 309 assigned to S-1). The full analysis set consisted of 286 patients in the taxane group and 306 in the S-1 group. Median follow-up was 34·6 months (IQR 17·9-44·4). Median overall survival was 35·0 months (95% CI 31·1-39·0) in the S-1 group and 37·2 months (33·0-40·1) in the taxane group (HR 1·05 [95% CI 0·86-1·27]; pnon-inferiority=0·015). The most common grade 3 or worse adverse events were neutropenia (20 [7%] of 307 patients in the S-1 group vs nine [3%] of 290 patients in the taxane group), fatigue (ten [3%] vs 12 [4%]), and oedema (one [<1%] vs 12 [4%]). Treatment-related deaths were reported in two patients in the taxane group.. S-1 is non-inferior to taxane with respect to overall survival as a first-line treatment for metastatic breast cancer. S-1 should be considered a new option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer.. Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan; Taiho.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Disease Progression; Disease-Free Survival; Docetaxel; Drug Combinations; Edema; Fatigue; Female; Follow-Up Studies; Health Status; Humans; Liver Neoplasms; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Rate; Taxoids; Tegafur

We evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, recommended dose for phase II (P2RD), and preliminary anticancer activity of a combination eribulin and S-1 therapeutic in metastatic breast cancer patients pretreated with anthracycline and taxane.. Patients aged 20-74 years were recruited. In level 1, patients received S-1 (65 mg m(-2)) from day 1 to 14, and eribulin (1.1 mg m(-2)) on day 1 and 8 in a 21-day cycle. In level 2, eribulin was increased to 1.4 mg m(-2). In level 3, S-1 was increased to 80 mg m(-2).. Twelve patients were enrolled into three cohorts. Planned dose escalation was completed, with one case exhibiting dose-limiting toxicity (grade 3 hypokalaemia) at level 3, without reaching the MTD. The P2RD was determined to be level 2 (eribulin 1.4 mg m(-2) and S-1 65 mg m(-2)). The most common grade 3 or 4 toxicity was neutropenia (83.3%), followed by febrile neutropenia (25.0%). Five of eleven patients (41.7%) with measurable disease had a partial response. Pharmacokinetics were characterised by dose-dependent elimination and nonlinear exposure.. Dose level 3 was not tolerated owing to febrile neutropenia development. Thus, intermediate dose level 2 was recommended for further evaluation. Preliminary antitumour activity warrants further investigation in this setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Furans; Humans; Ketones; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur; Young Adult

We conducted a phase I study of a weekly nab-paclitaxel and S-1 combination therapy in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer. The primary objective was to estimate the maximum tolerated and recommended doses. Each treatment was repeated every 21 days. Levels 1, 2a, 2b, and 3 were set depending on the S-1 dose (65 or 80 mg/m(2) ) and nab-paclitaxel infusion schedule (days 1 and 8 or days 1, 8, and 15). Fifteen patients were enrolled. Dose-limiting toxicity was observed in one patient at Level 3 (100 mg/m(2) nab-paclitaxel on days 1, 8, and 15 with 80 mg/m(2) S-1 daily for 14 days, followed by 7 days of rest). Although the maximum tolerated dose was not reached, the recommended dose was determined to be Level 3. Neutropenia was the most frequent grade 3-4 treatment-related adverse event. For patients with measurable lesions, the response rate was 50.0% and the median time to treatment failure and median progression-free survival was 13.2 and 21.0 months, respectively. The present results show the feasibility and potential for long-term administration of this combination therapy.

Topics: Adult; Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Receptor, ErbB-2; Tegafur

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.. Patients with MBC were randomly assigned to receive capecitabine 825 g/m(2) 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).. 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).. 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.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Capecitabine; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Japan; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyrimidines; Tegafur

S-1 is an oral cytotoxic preparation that contains tegafur. Gamma-butyrolactone (GBL) is a metabolite of tegafur that is known to suppress vascular endothelial growth factor (VEGF)-mediated angiogenic activity. The aim of this study was to determine the change in circulating endothelial cell (CEC) counts, GBL levels, and angiogenesis-related factors during S-1 administration in metastatic breast cancer (MBC) patients.. Patients with HER2-negative MBC were eligible. S-1 was administered orally twice daily in a 4 week on/2 week off cycle until disease progression or unacceptable toxicity occurred. Blood was collected on the following: days 1, 43, 85 (before each cycle of S-1 administration), days 15, 57 (1 h after S-1 administration), and day 29. The CellSearch(®) system was used to count the CECs. The gas chromatographic-mass spectrometric method was used to measure plasma GBL and 5-FU levels. Levels of VEGF were assayed by enzyme-linked immunosorbent assay.. A total of 18 patients were enrolled. The plasma GBL levels on days 15 and 57 were 41.3 ± 15.8 and 41.0 ± 11.2 ng/mL, respectively. The CEC levels decreased on day 15, and significantly low levels were maintained until day 85 (P = 0.002 vs day 1). The plasma VEGF levels significantly decreased on day 15 (P = 0.012 vs day 1) and had a tendency to decrease until day 57.. This exploratory study showed that GBL levels increased, VEGF levels decreased, and CEC levels were suppressed during S-1 administration. S-1 appears to have anti-angiogenic activity.

Topics: 4-Butyrolactone; Administration, Oral; Adult; Aged; Antigens, CD34; Antimetabolites, Antineoplastic; Breast Neoplasms; Cell Count; Chemokine CCL2; Drug Combinations; Endothelial Cells; Female; Fluorouracil; Humans; Middle Aged; Neovascularization, Pathologic; Oxonic Acid; Tegafur; Thrombospondin 1; Treatment Outcome; Vascular Endothelial Growth Factor A

We undertook a prospective phase II study to evaluate the efficacy of S-1 plus trastuzumab combination regimen for human epidermal-growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC).. HER2-positive MBC patients received oral administration of S-1 (80 mg/m2/day, days 1 to 28, every 6 weeks) and intravenous weekly trastuzumab (2 mg/kg), according to the results of a prior Phase I trial of our group.. A total of 28 patients were enrolled and received a median of 3.5 (range 1-10) cycles of treatment. Overall response rate and clinical benefit rate were 53.6% and 75.0%, respectively. Progression-free survival was 30 weeks. With regard to grade 3 and 4 adverse effects, leucopenia, neutropenia, increase in serum alanine aminotransferase, and diarrhea were observed.. Combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this trial.

Topics: Administration, Oral; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Prospective Studies; Receptor, ErbB-2; Tegafur; Trastuzumab

S-1 is a novel oral anticancer agent consisting of tegafur, a prodrug of 5-fluorouracil, and 2 modulators. A phase I study of sequential S-1 and cyclophosphamide(CPA)therapy was conducted to determine the dose-limiting toxicities(DLTs)and recommended doses(RDs)in patients with metastatic or recurrent breast cancer(MBC). Patients with MBC received sequential S-1 and CPA. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at escalating doses of 40, 50, 65, and 80mg/m2/day and CPA at 100 mg/body/day on days 15-28. The schedule was repeated twice at a 4-week interval. The purposes of this study were to determine the RDs, safety, and efficacy of the regimen. A total of 12 patients were registered. No patients experienced DLTs, and the RDs of S-1 and CPA were 80mg/m2/day and 100 mg/body/day, respectively. The response rate was 50. 0%. In conclusion, sequential therapy with S-1 and CPA could be safely and effectively used for the treatment of MBC, and the RDs for this regimen were determined to be 80mg/m2/day for S-1 and 100 mg/m2/day for CPA.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Recurrence; Tegafur

This study evaluated the efficacy and safety of S-1 combined with docetaxel (SD) following doxorubicin plus cyclophosphamide (AC) as neoadjuvant therapy in patients with HER2-negative, stage II-III breast cancer.. Patients received AC every 3 weeks for four cycles followed by S-1 (30 mg/m2 orally b.i.d. on days 1-14) and docetaxel (75 mg/m2 i.v. on day 1) every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR) rate in breast and axillary lymph nodes.. The study included 49 patients with a median age of 43 years. The median breast tumor size was 4.0 cm by palpation. All patients were positive for involvement of axillary lymph node and five patients also had supraclavicular lymph node metastasis, which was confirmed by histological examination. In total, 85.4% of patients (41/49) completed eight cycles of therapy and 95.9% of patients (47/49) received curative surgery. The pCR rate was 22.5% (n = 11). The clinical response rate was 67.4%. During SD chemotherapy, the most frequent grade 3-4 toxicity was neutropenia (8.5% by cycle). There was a single treatment-related mortality from severe neutropenia. Grade 3 S-1 specific toxicities such as epigastric pain (12.2% by person), stomatitis (4.1% by person), and diarrhea (2.0% by person) were also observed. In particular, gastrointestinal discomfort led to dose reduction of S-1 in 45.8% of patients.. Given all axillary lymph node positive diseases, neoadjuvant S-1 combined with docetaxel following AC showed a favorable anti-tumor activity but gastrointestinal discomfort should be carefully considered for future studies.. NCT00994968.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Docetaxel; Doxorubicin; Drug Combinations; Female; Humans; Induction Chemotherapy; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Risk Factors; Taxoids; Tegafur; Treatment Outcome; Tumor Burden

As there are no reports of S-1 in combination with trastuzumab in clinical settings, we evaluated the safety and efficacy of S-1 in combination with trastuzumab for human epidermal-growth factor receptor (HER2)-positive metastatic breast cancer (MBC) and determined the recommended dose (RD).. Patients with HER2-positive MBC received trastuzumab (a fixed initial dose of 4 mg/kg/day, then 2 mg/kg every week) plus S-1 (4 weeks followed by a 2-week rest) every 42 days. The dosage of S-1 was set of three levels (1: 80 mg/m², 2: 65 mg/m², 3: 50 mg/m²). The purposes of this study were the determination of the RD and safety. Dose-limiting toxicity (DLT) data were continually monitored to assess S-1 dose decreases.. Twelve patients were treated at level 1. Because no patients experienced DLT, the RD of S-1 plus trastuzumab therapy was 80 mg/m² S-1 and 4 mg/kg followed by 2 mg/kg trastuzumab. The overall response rate and disease control rate were 33.3% and 83.3%, respectively.. S-1 plus trastuzumab could be safely and effectively used for the treatment of HER2-positive MBC. The RD for a phase II study of this regimen was determined to be 80 mg/m² S-1 and 2 mg/kg trastuzumab every week (loading dose, 4 mg/kg).

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Female; Genes, erbB-2; Humans; Neoplasm Metastasis; Oxonic Acid; Tegafur; Trastuzumab

This randomized controlled trial will compare oral 5-fluorouracil derivatives, TS-1, with intravenous standard chemotherapy such as taxanes in women with metastatic or recurrent breast cancer. Patients with hormone-resistant breast cancer are assigned to either TS-1 (40-60 mg twice daily for 28 consecutive days, followed by a 14-day rest period) or standard chemotherapy (docetaxel 60-75 mg/m(2) at 3- or 4-week intervals, paclitaxel 175 mg/m(2) at 3- or 4-week intervals or paclitaxel 80-100 mg/m(2) weekly, followed by a 1-week rest period). Treatment will be repeated until tumor progression or > or =4 courses for TS-1 and > or =6 courses for taxanes. The primary endpoint is overall survival. Secondary endpoints are progression-free survival, time to treatment failure, adverse events, health-related quality of life and cost-effectiveness. A threshold hazard ratio of 1.333 will be used to determine whether overall survival in the TS-1 group is equivalent (not inferior) to that in the taxane group. The target number of registered patients is 600.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Cost-Benefit Analysis; Disease Progression; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Quality of Life; Survival Rate; Taxoids; Tegafur

It is extremely difficult to bring about a complete cure of metastatic breast cancer: the purpose of treatment is to prolong the patient's survival while maintaining their quality of life (QOL). The current retrospective study was conducted to find whether S-1, an orally administered 5-FU agent, can produce a therapeutic result in patients with recurrent metastatic breast cancer while maintaining their QOL.. Among the patients who were diagnosed at our institution to have recurrent metastatic breast cancer between November 2001 and December 2008, those who were treated with S-1 were selected and their records retrospectively reviewed.. The analysis was conducted on 33 patients. The median number of regimens that these patients underwent was 2 (range 0-6). The overall response rate (ORR), clinical benefit rate (CBR), median time to treatment failure and overall survival were 30%, 42%, 152 days and 338 days, respectively. Among the 11 patients who were treated with S-1 in the first or the second line, ORR and CBR were 45.5 and 63.6%, respectively. Toxicity more than grade 3, leucopenia, neutropenia diarrhea, mucositis, and hand-foot syndrome were found in only 3%.. S-1 is well-tolerated by patients, promising a therapy while maintaining their QOL. When applied in the early stage of a disease in particular, the agent promises a very effective anti-tumor effect.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome

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.

Topics: Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Breast Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Tegafur; Vomiting, Anticipatory

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.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pyridines; Tegafur; Treatment Outcome

S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), which is a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) activity; and potassium oxonate (Oxo), which reduces gastrointestinal toxicity. Phase I and early Phase II clinical trials have already been completed. On the basis of the results of these trials, 80 mg/m2/day, given daily in two divided doses after breakfast and supper, a 28-day consecutive oral regimen is recommended. In this study, we investigated the pharmacokinetics of 5-FU, intact FT, CDHP, and Oxo, after administration of S-1, at a standard dose of 80 mg/m2/day, in advanced cancer patients. Twelve patients were recruited to the study; 5 patients with gastric cancer, 4 with colorectal cancer, and 3 with breast cancer. Among them, analysis was conducted on 12 patients for single administration and on 10 patients for consecutive administration. The initial dose of S-1 for each patient was determined according to his/her body surface area (BSA) as follows: for BSA < 1.25 m2, 80 mg/body/day; for 1.25 m2 < or = BSA < 1.5 m2, 100 mg/day; and for 1.5 m2 < or = BSA, 120 mg/day. For single administration, half of the standard dose was used. For 28-day consecutive administration, the standard dose was given daily in two divided doses. The average single dose per BSA was 35.9 mg/m2 (31.7-39.7 mg/m2). Pharmacokinetic parameters of plasma 5-FU were as follows: Cmax, 128.5 +/- 41.5 ng/ml; Tmax, 3.5 +/- 1.7 h; AUC(0-14), 723.9 +/- 272.7 ng x h/ml; and T(1/2), 1.9 +/- 0.4 h. In the 28-day consecutive regimen, there were no fluctuations in pharmacokinetics nor any drug accumulation. Because the pharmacokinetics of orally administered S-1 is almost similar to that of continuous i.v. infusion of 5-FU, we concluded that S-1 may improve patients' quality of life.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Colorectal Neoplasms; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Neoplasms; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Remission Induction; Survival Analysis; Tegafur

Locally advanced breast cancer sometimes results in a large chest wall defect at mastectomy. When closing the wound horizontally, the skin tension is usually severe in the middle of the wound, while the skin of the lateral area tends to make a dog-ear deformity. Triangle technique is a procedure to prevent the dog ear in which the skin and subcutaneous fat of the axilla are cut into an equilateral triangle. Herein, we present a case of breast cancer who underwent a mastectomy and closed the wound with a skin graft by utilizing the skin removed from lateral thoracic area using triangle technique. An 85-year-old female visited our institution complaining about the mass on her right breast. Preoperative images showed a 10 cm-sized mass with suspicious axillary and mediastinal lymph nodes swelling. A biopsy revealed a hormone receptor-negative, HER2-positive invasive ductal carcinoma. A mastectomy and axillary lymph node sampling were performed for a local control as the tumor did not respond to four cycles of triweekly trastuzumab combined with S-1. After a transverse elliptical incision, a skin of the lateral thoracic area was harvested using triangle technique. As the middle of the wound had excessive closing tension, the skin was grafted on the defect. After 10 day fixation by a tie-over dressing, the wound healed without complications. This procedure is a simple method for closing a large defect after mastectomy preventing both the dog-ear deformity and a new wound scarring of a donor site.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents, Immunological; Axilla; Biopsy; Breast Neoplasms; Carcinoma, Ductal; Drug Combinations; Female; Follow-Up Studies; Humans; Lymph Nodes; Mammaplasty; Mastectomy; Oxonic Acid; Skin Transplantation; Surgical Flaps; Tegafur; Thoracic Wall; Trastuzumab; Treatment Outcome

The previous randomized phase 3 trial (SELECT BC) showed that S-1 as a first-line chemotherapy for metastatic breast cancer (MBC) is non-inferior to taxane with respect to overall survival. This study aimed to identify the usefulness of metabolism-related genes as predictive biomarkers for the response to S-1 compared with taxane using tumor tissue samples from the previous trial.   PATIENTS AND METHODS: In this SELECT BC-EURECA study, 147 patients with human epidermal growth factor 2 (HER2)-negative MBC who received either S-1 or taxane were evaluated. Formalin-fixed paraffin-embedded specimens were collected, and 14 genes involved in the pyrimidine metabolic pathway, estrogen receptor, progesterone receptor, HER2, Ki67, and beta-tubulin were measured using reverse transcription polymerase chain reaction in microdissected tumor specimens. The expression of each gene was categorized as low, intermediate, and high by tertile values.   RESULTS: Interaction tests to identify biomarkers for the response to S-1 compared with taxane, revealed the following as the top 3 biomarkers: RRM1 (P value = 0.24), GGH (P value = 0.25), and MTHFR (P value = 0.28). In the S-1 group, lower GGH and higher MTHFR expression were significantly correlated with better time to treatment failure. In the taxane group, there was no gene that was identified as a significant indicator of treatment failure.. This biomarker analysis from SELECT BC did not identify any predictive biomarkers for the response to S-1 compared with taxane. Future studies with larger sample size and information on not only mRNA, but also protein and DNA for broad functional analyses are needed.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Health Status; Humans; Oxonic Acid; Receptor, ErbB-2; Receptors, Estrogen; Tegafur

S-1, a 5-fluorouracil(5-FU) oral anti-cancer drug, has been traditionally used with a schedule of 4-week oral administration followed by 2-week rest for breast cancer treatment. We, herein, aimed to investigate the clinical efficacy and safety of a schedule of 2-week oral administration followed by 1-week rest for patients with metastatic breast cancer.. We enrolled patients with HER2-negative metastatic breast cancer who had not received prior chemotherapy. S-1 was administered consecutively for 2-weeks followed by a 1-week rest.. Between September 1, 2013 and August 31, 2016, 32 patients were enrolled. The median follow-up time was 32.1 months. The median progression-free survival (PFS) was 9.4 months. Overall survival (OS) was 41.0 months, time to treatment failure (TTF) was 7.8 months, response rate (RR) was 31.3%, and disease control rate (DCR) was 78.1%. The incidence of grade 3 side-effects was not high.. The 3-week schedule of S-1 can be considered useful as a treatment for patients with metastatic breast cancer, helping in maintaining a high quality of life.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

Irinotecan is rarely used on the metastatic breast cancer (MBC) setting. S-1 is an oral mixture of tegafur, gimeracil and oteracil. We conducted this pilot study to assess efficacy and safty of chemotherapy with combined irinotecan and S-1 (IRIS).. Twenty-two patients were enrolled in the study. Median age was 50.5 years (range=26-72). Nineteen patients were evaluable for response. Median overall survival and progression-free survival were 672 days (95% CI=420-967) and 166 days (95% CI=76-814), respectively.. The IRIS regimen has an acceptable safety profile and modest efficacy against MBC in patients previously heavily treated with chemotherapy. This regimen has potential to treat MBC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Middle Aged; Oxonic Acid; Pilot Projects; Progression-Free Survival; Tegafur

Metaplastic squamous cell carcinoma(MSCC)of the breast is very unusual and is histologically characterized by rapid progression. Conventionalchemotherapy for ductalcarcinoma of the breast is ineffective against MSCC. Here, we report a case of MSCC of the breast successfully treated with S-1. A 57-year-old woman was admitted to our hospital because of a left breast tumor. A tumor approximately 10 cm in diameter was palpable in the lower-outer quadrant(D region)of the left breast. Core needle biopsy indicated estrogen receptor(ER)-negative, progesterone receptor(PR)-negative, and human epidermalgrowth factor receptor 2(HER2)-negative MSCC of the breast. Computed tomography(CT)showed left axillary lymph node metastases but did not indicate distant metastasis. A diagnosis of T4N3cM0, Stage ⅢC, MSCC of the left breast was made. Each treatment course consisted of the administration of S-1(120mg/body/day)for 4weeks, followed by 2 drugfree weeks. After the second course, significant tumor and lymph node reduction was observed. We concluded that S-1 chemotherapy seems to be effective for patients with MSCC of the breast.

Topics: Antimetabolites, Antineoplastic; Axilla; Biopsy, Large-Core Needle; Breast Neoplasms; Carcinoma, Squamous Cell; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Receptors, Estrogen; Tegafur

Although S-1 is an effective oral anticancer drug in patients with metastatic breast cancer, it is difficult for some patients to continue taking S-1 because of its side effects in the approved regimen of 4 weeks of administration followed by a 2-week rest. When S-1 is administered for 5 days followed by a 2-day rest(5-day on/2-day off), the drug concentration is almost equal to that of the approved regimen, and it can be administered for longer without deterioration of its clinical effect. We retrospectively analyzed the effect and safety in 25 cases in which S-1 was administered using the "5-day on/2-day off" regimen in patients with metastatic breast cancer between November 2006 and August 2014 in our hospital. Patients were all female, and their median age was 68 years(44-87). ER was positive/negative in 15/10 cases, and PS 0/1/2were found in 8/ 10/7 cases. They had no prior chemotherapy and had measurable lesions. S-1 was administered at a dose of 80mg/m2 twice a day on a "5-day on/2-day off" schedule and was reduced when its side effects were appeared. The median treatment duration was 25(3-214)weeks, and CR/PR/long SD/SD/PD as clinical responses were observed in 0/8/5/5/7 cases. The overall response rate was 32% and clinical benefit rate was 52%. There was no difference in response rates whether visceral metastases were present or not. In terms of hematologic toxicity, anemia was seen in one case, and there were no cases of neutropenia. In non-hematologic toxicity, no more than Grade 3 side effects were shown. Discontinuance was observed in only one case because of diarrhea. A "5-day on/2-day off" regimen of S-1 in metastatic breast cancer is well tolerated, and we can continue administering it to elderly patients or those with poor PS without reducing QOL; thus, it can be considered as one of the effective metronomic treatments. In the future, a prospective study is warranted to ascertain these results.

Topics: Adult; Aged; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Prospective Studies; Retrospective Studies; Tegafur

While some studies show improved outcomes in clinical trial participants as compared to non-participants, existence of such a trial effect has not been proved precisely.. This was a prospective cohort study to compare the prognoses for participants in the randomized controlled trial (SELECT BC) and non-participants. SELECT BC compared S-1 and taxane as first-line treatment for metastatic breast cancer. Non-participants were all patients who met the eligibility criteria of SELECT BC and who had been requested to participate in that trial by attending doctors and declined. The study aimed to compare the prognoses between participants and non-participants. The primary endpoint was median overall survival.. The median OS in participants was significantly superior to that in non-participants with a statistically significant difference (36.8 months vs. 25.2 months. HR 1.48, p = 0.022). A similar result was obtained when only patients who received the same chemotherapy (S-1 or taxane) used in SELECT BC after declining participation were assumed as non-participants (36.8 months vs. 22.0 months. HR 2.03, p = 0.006).. This study may suggest the existence of a trial effect, in which, for a given treatment, participation in a clinical trial is associated with a better outcome.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Bridged-Ring Compounds; Combined Modality Therapy; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Outcome Assessment, Health Care; Oxonic Acid; Patient Participation; Randomized Controlled Trials as Topic; Survival Rate; Taxoids; Tegafur; Treatment Outcome

To observe and analyze the therapeutic efficacy of S-1 monotherapy in the treatment of advanced breast cancer in elderly patients. A total of 180 elderly patients diagnosed as advanced breast cancer and treated at our hospital were enrolled. All patients were randomized into study group and control group, with 90 patients in each group. Of those, capecitabine monotherapy was administered in control group, while S-1 monotherapy was applied in study group. Clinical efficacy and safety of both groups were compared. By comparing recent therapeutic effects, results showed that the overall treatment efficacy was 51.11% in study group, while the value was 35.56% in control group, suggesting a higher therapeutic efficacy in study group (P<0.05). Also, the incidence of side effects was significantly lower in study group compared with control group (P<0.05). Moreover, quality of life was better preserved in study group (P<0.05). S-1 monotherapy was relatively effective and safe in the treatment of advanced breast cancer in elderly patients.

Topics: Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Capecitabine; Drug Combinations; Female; Fluorouracil; Humans; Middle Aged; Oxonic Acid; Quality of Life; Tegafur; Treatment Outcome

Topics: Administration, Oral; Aged; Breast Neoplasms; Capecitabine; Cardiotoxicity; Colorectal Neoplasms; Coronary Vasospasm; Drug Combinations; Drug Substitution; Female; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

We assessed the impact of treatment preferences in second-line chemotherapy on breast cancer prognosis using the SELECT BC study.. The SELECT BC study was performed in patients with HER2-negative metastatic breast cancer treated with initial chemotherapy. From these patients, 618 were assigned to 2 groups (S-1 group, 309; taxane group, 309). The S-1 and taxane groups were each subdivided into 3 groups: crossover group, protocol-recommended group, and other group, and the analysis of overall survival (OS) was performed using Cox regression with inverse probability weighting, to adjust for postrandomization confounding.. In the taxane group, the OS of the crossover group (39.6 months) was better than that of the protocol-recommended group (35.7 months) and the other chemotherapy group (36.9 months) (vs. the protocol-recommended group, HR 0.72 [95% CI 0.52-0.98], p = 0.037; vs. the other chemotherapy group, HR 0.71 [95% CI 0.43-1.18], p = 0.183). In the S-1 group, there was no statistically significant difference in OS between the 3 groups.. The study of the combination of first-line chemotherapy and second-line chemotherapy showed that S-1 might be recommended as a second-line chemotherapy in patients in whom taxane was the primary chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Prognosis; Receptor, ErbB-2; Taxoids; Tegafur; Young Adult

This study evaluated the cost-effectiveness of replacing standard intravenous therapy (taxane) with oral S-1 therapy for first-line metastatic breast cancer treatment.. This cost-effectiveness analysis was based on data from a randomized phase III trial (SELECT BC). As cost-effectiveness was a secondary endpoint of the SELECT BC trial, some of the randomized patients participated in an EQ-5D survey (N = 391) and health economic survey (N = 146). The EQ-5D responses, claims, and prescription data were collected for as long as possible until death. The expected quality-adjusted life years (QALY) obtained from each treatment were calculated using patient-level EQ-5D data, and the expected cost was calculated using patient-level claim data. The analysis was performed from the perspective of public healthcare payers.. The estimated EQ-5D least-square means and 95% CI up to 48 months were 0.764 (95% CI, 0.741-0.782) and 0.742 (95% CI, 0.720-0.764) in the S-1 and taxane arms, respectively. The expected QALY was 2.11 for the S-1 arm and 2.04 for the taxane arm, with expected costs of JPY 5.13 million (USD 46,600) and JPY 5.56 million (USD 50,500), respectively. These results show that S-1 is cost-saving. According to probabilistic sensitivity analysis, S-1 was dominant with a probability of 63%. When the willingness to pay (WTP) value was JPY 5 million (USD 45,500) per QALY, the probability of being cost-effective was 92%.. Our results show that the introduction of oral S-1 therapy for metastatic breast cancer is highly likely to be cost-effective.. UMIN CTR C000000416 . Registered on May 10, 2006.

Topics: Antimetabolites, Antineoplastic; Biomarkers, Tumor; Breast Neoplasms; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Drug Combinations; Female; Humans; Japan; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Tegafur; Treatment Outcome

We report the case of a patient in which S-1 plus anastrozole was administered as first-line chemotherapy for Stage IV breast cancer with skin invasion, multiple lymph node metastasis, and lymphangitis carcinomatosis. A 77-year-old woman had a mass destroyed immediately outside the axilla with dry coughs. An 11mm unpalpable mass in the right breast and an axillary mass were confirmed to be scirrhous carcinoma(Luminal type B), respectively, by core needle biopsy. In one course, S- 1(100mg/day)therapy involves taking 2 courses of 14 days of administration and 7 days off the drug. Anastrozole(1mg/ day)was administered daily. After completion of one course, marked shrinkage of the axillary tumor and supraclavicular lymph node, and lightness of coughing was observed. The metastatic lymph nodes and pulmonary metastatic lesions reduced in size by over 30%, as revealed using CT. The adverse event was only grade 1 pigmentation and lacrimation. Ten months later, the self-destructed skin was completely scarred, and metastatic lesions had maintained their reduction in size. According to the results of the SELECT BC study, S-1 as primary chemotherapy for breast cancer is an evidence-based drug that can reduce the decrease in QOL, such as hair loss, and it can be positively selected.

Topics: Aged; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Breast Neoplasms; Drug Combinations; Female; Humans; Lymphatic Metastasis; Nitriles; Oxonic Acid; Tegafur; Triazoles

Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy.. The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently.. Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed.. The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.

Topics: Adult; Aged; Anthracyclines; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Tegafur

We report a case of Stage IV breast cancer in a 62-year-old woman who responded well to alternate-day S-1/letrozole combination therapy. She was admitted to our hospital because of appetite loss and vomiting, and was diagnosed with invasive lobular carcinoma (ER+/HER2-) with gastric metastasis. After gastrointestinal stenting was performed, we initiated oral administration of S-1 (100 mg/body) and letrozole (2.5 mg) as systemic therapy. To reduce adverse effects, we administered S-1 on alternate days. Computed tomography and endoscopic examination revealed that the patient has been showing partial response since 1 year after initiating treatment. Therefore, we conclude that alternate-day S-1/letrozole combination therapy could be an effective and sustainable treatment for advanced ER-positive, HER2-negative breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Lobular; Drug Combinations; Female; Humans; Letrozole; Middle Aged; Nitriles; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Triazoles

The treatment efficacy of advanced breast cancer is still not promising. This study aimed to compare the efficacy and safety of docetaxel/S-1 (DS1) versus docetaxel/capecitabine (DX) as the first-line treatment for advanced breast cancer.From June 2008 to June 2013, 22 patients with advanced breast cancer were treated with the DS1 regimen. Another 26 age- and disease status-matched patients treated with the DX regimen served as controls. The 2 groups were compared in terms of time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety profiles.Median TTP did not differ significantly between the DS1 group and the DX group (9.04 vs 10.94 months, P = 0.473). There were no significant differences in objective response rate, disease control rate, and clinical benefit rate between the 2 groups. Both the DS1 and the DX regimens showed good tolerability. The 2 regimens showed no significant difference in adverse events except degree III hand-foot syndrome (DS1 0 vs DX 23.1%, P = 0.025).For the first-line treatment of advanced breast cancer, the DS1 and the DX regimens showed similar efficacy and safety. The DS1 regimen had less severe hand-foot syndrome than the DX regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Disease Progression; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Taxoids; Tegafur

To clarify the tolerance and pharmacokinetics of combined therapy with S-1 and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic or recurrent breast cancer.. From January 2008 through to September 2009, combined therapy with S-1 and trastuzumab was given to 7 patients with HER2-positive metastatic or recurrent breast cancer. The incidence of adverse events and the pharmacokinetics of tegafur, 5-fluorouracil, and gimeracil in plasma were studied.. One patient had grade 3 leukopenia, and another had a grade 3 elevation of alanine aminotransferase. All other adverse events were grade 2 or lower. The combination of S-1 and trastuzumab did not cause any new adverse events. The incidence of adverse events was similar to those associated with S-1 alone. The median number of treatment cycles was 11. The pharmacokinetics of tegafur, 5-fluorouracil, and gimeracil after treatment with S-1 plus trastuzumab did not markedly differ from those after S-1 alone.. Combined therapy with S-1 and trastuzumab did not cause any new adverse events, administration continuity was good, and the therapy was well tolerated.

Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Feasibility Studies; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Receptor, ErbB-2; Tegafur; Trastuzumab

The randomized-controlled trial is widely accepted as a clinical trial to decide a standard therapy. It remains to be concluded whether or not patients benefit from participation itself in a randomized-controlled trial. This study was aimed at comparing prognoses between trial participants and participation-refusers. Concerned randomized trials are 'selection of effective chemotherapy for breast cancer' (SELECT BC) and its successor trial, SELECT BC-CONFIRM. Study subjects are all of metastatic breast cancer patients who are requested by their doctors to participate in these two trials. This trial is a hitherto exceptional prospective study and is suitable to clarify the effects of participation per se in such a trial on prognosis when compared with previous two studies.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cohort Studies; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Oxonic Acid; Patient Participation; Patient Selection; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Research Subjects; Selection Bias; Taxoids; Tegafur

Squamous cell carcinoma of the breast is uncommon, but that of the nipple skin is rarer. The effect of chemotherapy in these cases is yet to reach consensus. We report a rare case in which primary squamous cell carcinoma of the nipple skin was successfully treated with S-1 alone. A 64-year-old woman was admitted to our hospital because of a granulomatous tumor mass over the right nipple, which she was aware of for 10 years; the tumor showed a rapid increase in growth before admission. The tumor was approximately 4 cm at the first visit, and was diagnosed as squamous cell carcinoma by incisional biopsy. We administered preoperative systemic chemotherapy owing to the presence of metastasis in an axillary lymph node. After 2 courses of chemotherapy with oralS -1 at 100mg/day for 28 days followed by a 14-day resting period, the primary tumor and metastatic lymph node showed a remarkable reduction in size. The patient subsequently underwent a radical operation and is currently healthy without any recurrence.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Breast Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Middle Aged; Nipples; Oxonic Acid; Tegafur

TS-1, an oral fluoropyrimidine, is known to be effective for the treatment of various carcinomas including advanced/metastatic breast cancer.The Kumamoto Breast Cancer Cooperative Group(KBCCG)conducted an observational study, wherein, the efficacy and safety of TS-1 monotherapy was analyzed in 35 patients with recurrent or metastatic breast cancer.The median time to cancer progression was 3.7 months, overall response rate was 12%, and clinical benefit rate was 32%. Adverse events were observed in 27 patients(77%), and adverse events of Grade >3 were observed in 7 patients(20%). The rate of treatment-related Grade 3 and 4 adverse events increased, and was associated with poor levels of creatinine clearance(Ccr)ie <60mL/min.This study suggests that TS-1 monotherapy can potentially be used as a salvage treatment for advanced/metastatic breast cancer owing to its safety and efficacy.Measuring the level of Ccr before TS-1 therapy should be considered to avoid severe adverse events.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur

Tegafur-gimeracil-oteracil potassium (TS-1)is a drug that is used mainly as a third-line treatment or beyond for metastatic breast cancer(MBC). However, there is still insufficient evidence on its clinical effectiveness, and there are very few reports on clinical research using TS-1 up front. In this report, we examined the effectiveness and safety of TS-1 therapy for MBC.. The subjects were 46 patients with MBC who were treated with TS-1 between January 2005 and January 2013. These patients were retrospectively examined.. The objective response rate to TS-1 therapy was 30.4%, clinical benefit rate (CBR)was 50.0%, and the median time to treatment failure was 10.7 months. When examined by site, the CBR was high locally (46.2%), in the lymph nodes (40.7%), in the bone (42.9%), and in the lungs and pleura (44.8%). However it was low in the liver(30.0%). The relationship was examined between clinicopathological factors and the effectiveness of TS-1 therapy. The objective response rate (ORR) was significantly higher for patients with disease-free interval (DFI) of 2 years or more (p=0.039), TS-1 therapy used as third-line treatment or earlier (p=0.022), negative HER2 status (p=0.020), and no history of capecitabine (CAP)therapy (p=0.049). The CBR was significantly higher for patients with no visceral metastasis (p=0.032), TS-1 used as third-line treatment or earlier (p=0.019), negative HER2 status (p= 0.045), no history of CAP therapy (p=0.006), and no history of tegafur-uracil/doxifluridine therapy (p=0.031). Multivariate analysis showed that DFI of 2 years or more (p=0.035, odds ratio:0.104)was an independent predictor of effectiveness assessed by ORR. There were only 4 patients in whom the treatment was discontinued due to adverse event, and TS-1 was generally well tolerated.. TS-1 was highly effective and well tolerated by patients with MBC. Its up-front use might enable the maintenance of satisfactory QOL and the enhancement of its clinical effectiveness.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pyridines; Retrospective Studies; Tegafur

We here describe a case of Stage IV breast and gastric cancer in which S-1/paclitaxel therapy was effective in maintaining the patient's QOL. A 50-year-old woman visited our hospital with complaints of her right breast tumor and right brachialgia. She was diagnosed with breast cancer with multiple bone metastases including cervical vertebrae. Accordingly, local radiation therapy and tamoxifen(TAM)administration was started immediately. Gastrointestinal endoscopy revealed gastric cancer, but laparotomy disclosed the gastric cancer was unresectable. At that time, the complaints of pain, nausea, and fatigue had increased and S-1/paclitaxel therapy was started immediately. The treatment reduced the size of the lesions in the breast and stomach and improved the QOL without serious adverse events. We have been maintaining partial response(PR)in this patient for 28 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

For a case of recurrent breast cancer with multiple bone metastasis, an oral pyrimidine fluoride-based anti-cancer drug S -1, and zoledronic acid(a third-generation bisphosphonate formulation), were prescribed in experiments to test their efficacy. S-1 was prescribed orally at doses of 100 mg/day(twice)over a 4-week period with a cessation period of 2 weeks. Zoledronic acid was commenced with a strict administration of 4 mg every 4 weeks, taken intravenously. At the conclusion of the 1st S-1 course, the tumor markers began to improve to a certain extent with an improvement in the symptoms. Following the 16 courses, there was no abnormal accumulation detected by PET. Now, at the end of the 21st course, the treatment is being continued, and there has been no recurrence of inflammation or reoccurring growth detected. No adverse effects of more than Grade 1 occurred during the elapsed process. As a form of combined therapy, we can expect zoledronic acid to be a good anti-cancer drug because of its effectiveness and tolerability in treating recurring breast cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Drug Combinations; Female; Humans; Imidazoles; Oxonic Acid; Recurrence; Tegafur; Zoledronic Acid

We report our experience with two cases of postoperative multiple liver metastases that were reduced remarkably by S-1, VNR, and MPA combination therapy for breast cancer. A case diagnosed as Stage II B(T2, N1, M0)breast cancer was treated postoperatively with LH-RH agonist and TAM. Another case, diagnosed as Stage III B(T4b, N2, M0), was treated with postoperative CE therapy. Tumor markers were normalized and liver metastases were shrunk significantly in both cases which received combination chemotherapy of S-1, VNR, and MPA as first-line therapy after recurrence. We conclude that this combination chemotherapy is a useful regimen for metastatic breast cancer patients, because it can be continuously implemented over a long period of time while maintaining high QOL without serious adverse events.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Gonadotropin-Releasing Hormone; Humans; Liver Neoplasms; Medroxyprogesterone; Middle Aged; Oxonic Acid; Tamoxifen; Tegafur; Vinblastine; Vinorelbine

Here, we report the case of a patient with recurrent breast cancer and multiple liver metastases who showed complete remission (CR) after S-1 plus trastuzumab therapy. A 54-year-old woman with stage IIIA left breast cancer received 4 courses of epirubicin hydrochloride plus cyclophosphamide hydrate therapy and 4 courses of paclitaxel therapy as initial treatment after mastectomy. At 10 months after surgery, the carcinoembryonic antigen (CEA) level increased to 79.0 ng/mL, and multiple liver metastases were detected on close examination. Subsequently, the patient received S-1 plus trastuzumab combination therapy. The CEA level returned to normal after 2 courses of the combination therapy, and the liver metastases disappeared after 5 courses of therapy. CR has been maintained for 1 year and 3 months after the initiation of treatment. Because the present treatment has superior tolerability and safety, it is considered an effective option for treating recurrent breast cancer.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Drug Combinations; Female; Humans; Liver Neoplasms; Mastectomy; Middle Aged; Neoplasm Staging; Oxonic Acid; Recurrence; Tegafur; Trastuzumab

A resected case of complete response after treatment with S-1 for recurrent squamous cell carcinoma component of the breast is presented.A 65-year-old woman was admitted to another hospital because of a left breast tumor. A tumor approximately 6 cm in diameter was palpable in the subareolar-lower (DBE) region of the left breast; the diagnosis was breast cancer. We performed mastectomy and axillary lymph node dissection. The pathological diagnosis revealed squamous cell carcinoma of the left breast(pT3N1M0, Stage III A). FEC chemotherapy, a standard chemotherapy regimen for general breast cancer, was performed as first-line adjuvant therapy, but was withdrawn after 1 course due to sepsis shock. Weekly PTX chemotherapy as second-line treatment was also withdrawn after six courses due to interstitial pneumonia. Few skin rashes were observed along the incision scar of the left breast, but biopsy revealed skin invasion by local recurrence of squamous cell carcinoma of the breast. Treatment with S-1 was performed for 8 months, and she underwent resection of left skin, fat tissue, and underlying muscle, including the recurrent region. No residual primary carcinoma foci was found in the resected specimen; therefore, the pathological diagnosis revealed complete response for the squamous cell carcinoma component.

Topics: Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Humans; Neoplasm Staging; Oxonic Acid; Recurrence; Tegafur

The patient was a 75-year-old woman. Her chief complaint was edema in the right upper arm since December 2009. The right breast displayed a skin ulcer. The local findings were apparent in the right breast and the right axilla, and palpation revealed a mass under the skin ulcer that was diagnosed as papillotubular carcinoma by needle biopsy. The classification was T4bN1M1, stage IV, ER (+), PgR (+), and human epidermal growth factor receptor type 2 score 0. Because of failed cardiac function and lubricity, S-1(80 mg/body) and letrozole(2.5 mg/po) were administered. Lymph node reduction, disappearance of ulcerated skin, tumor reduction, and upper arm lymphedema were improved markedly after drug administration, and the tumor marker level decreased. Chemotherapies cause significant side effects, and the use of medicine in elderly patients with advanced breast carcinoma is limited. A clinical partial remission was achieved by administration of S-1 as the third-line therapy. Therefore, first-line administration of S-1 may be effective in such cases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Breast Neoplasms; Drug Combinations; Female; Humans; Letrozole; Middle Aged; Neoplasm Staging; Nitriles; Oxonic Acid; Tegafur; Treatment Outcome; Triazoles

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Breast Neoplasms; Capecitabine; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Humans; Molecular Targeted Therapy; Oxonic Acid; Tegafur

The present preclinical study was designed to evaluate a new combination therapy comprised of the aromatase inhibitor anastrozole (ANA) and the oral fluoropyrimidines, UFT and S-1 against the estrogen receptor (ER)-positive human breast cancer cell line MCF-7/Arom 14, which was stably transfected with the cDNA of human aromatase. MCF-7/Arom 14 cells showed a high aromatase activity and notably were able to grow in the presence of testosterone and estradiol (E(2)) in vitro. ANA and 5-fluorouracil (5-FU) inhibited cell growth at concentrations of 0.005-10 and 0.2-5 μM, respectively, and the combination of both drugs additively inhibited cell growth. The growth of MCF-7/Arom 14 tumors was significantly inhibited by ANA and S-1 or UFT in vivo. The combination of ANA with S-1 or UFT administered using a 21-day consecutive, metronomic-like regimen significantly enhanced the antitumor efficacy, suppressing tumor growth for 2-4 times longer than monotherapy. To investigate the mechanisms by which S-1 enhances the antitumor activity of ANA, the protein and mRNA expression levels of ER-α in tumor tissue after treatment with S-1, ANA, and the typical chemotherapeutic agents doxorubicin (ADM) or paclitaxel (TXL) were analyzed. The protein and mRNA expression levels of ER-α in the tumor tissue were markedly decreased after treatment with S-1 or S-1 + ANA, but not after treatment with either ADM or TXL. The reduced ER-α level after S-1 treatment might contribute to the increased antitumor activity of ANA by reducing ER-α-induced growth signaling in addition to the decrease in estrogen production induced by ANA. Based on these results, the combination of ANA and S-1 might yield a greater benefit than other chemotherapeutic agents in postmenopausal women with ER-positive breast cancer.

Topics: Anastrozole; Animals; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Blotting, Western; Breast Neoplasms; Cell Proliferation; Doxorubicin; Drug Combinations; Estrogen Receptor alpha; Estrogens; Female; Fluorouracil; Humans; Immunoenzyme Techniques; Mice; Mice, Inbred BALB C; Mice, Nude; Nitriles; Oxonic Acid; Paclitaxel; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tegafur; Transplantation, Heterologous; Triazoles; Tumor Cells, Cultured; Uracil

We report a 50-year-old female with pulmonary metastases from breast cancer who responded to S-1. In September 2003, she underwent surgery for breast cancer. Four years 8 months after the operation, lung relapse was detected. After the treatment failure of FEC60 (5-FU 500 mg/m², epirubicin 60 mg/m², cyclophosphamide 500 mg/m²) and taxane antitumor drugs, oral administration of S-1 80 mg/body/day was initiated. At the end of three courses, thoracic CT revealed the disappearance of the lung metastasis. Advanced reactions during the administration period were mild. After 14 courses of S-1 therapy (during 11 months), a complete response was clinically maintained. S-1 showed a good antitumor effect and tolerance, and it might be useful for treating metastatic and recurrent breast cancers.

Topics: Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Tegafur; Tomography Scanners, X-Ray Computed

We report a case of possible retroperitoneal metastasis of breast cancer successfully treated with oral S-1 and cyclophosphamide therapy after docetaxel and cyclophosphamide (TC) therapy. A 57-year-old woman with a history of bilateral breast cancer showed an increase in tumor markers during treatment with oral anastrozole as postoperative adjuvant therapy 4 years after her second cancer surgery. After careful examination, the patient was diagnosed as having multiple bone metastases and her medication was changed to oral letrozole. After 3 months, the patient developed left back pain and was referred to our hospital. CT scanning showed an enhanced mass in the region from the left perirenal and posterior pararenal spaces to the left psoas major muscle and the anterior aspect of the left iliacus muscle, suggesting retroperitoneal metastasis. TC therapy was performed and, as a result, tumor markers decreased and the mass disappeared on CT imaging. After discontinuation of TC therapy, the tumor markers increased again, following which oral S-1 and cyclophosphamide therapy were administered, and the tumor markers decreased. At the time of this writing, the patient is still undergoing therapy, and no recurrence has been observed. We concluded that oral S-1 and cyclophosphamide therapy were useful in the present case and were associated with few adverse effects.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Docetaxel; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Retroperitoneal Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

We experienced a case of endocrine therapy-resistant recurrent breast cancer with liver and bone metastases, treated with S-1 as first-line chemotherapy and maintaining a good quality of life. The patient was a 31-year-old premenopausal woman. She was diagnosed with cancer of the left breast(T1(18mm), N0, M(-))and underwent breast-conserving surgery, sentinel lymph node biopsy, and radiation therapy in August 2002. As there was hormone sensitivity, she was treated with LHRH analog for 3 years and tamoxifen for 5 years as adjuvant therapy. After her first childbirth, she had a recurrence of liver and bone metastases. After treatment with endocrine therapy failed, an oral administration of S-1 was initiated as first-line chemotherapy considering her QOL. She received 8 months of S-1 therapy with no severe adverse reactions and maintained a high quality of life. Treatment with S-1 is thought to be useful for first-line chemotherapy if the treatment demonstrates a therapeutic equivalence with taxane on patients' overall survival.

Topics: Adult; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Oxonic Acid; Quality of Life; Tegafur; Tomography, X-Ray Computed

The patient was a 55-year-old woman undergoing surgery for T2, N1, M0, stage II B breast cancer in November 1997. UFT and tamoxifen were administered as adjuvant chemotherapy. S-1 and zoledronic acid were then administered for the recurrence of multiple bone metastasis detected in January 2008. A significant improvement was achieved, and a long-term positive effect was confirmed until an exacerbation of bone metastasis in February 2010. S-1 and zoledronic acid therapy have few adverse drug reactions, they promptly manifest their effect, and are favored as a first choice for treating bone metastasis of breast cancer.

Topics: Antimetabolites, Antineoplastic; Biomarkers, Tumor; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Drug Combinations; Female; Humans; Imidazoles; Middle Aged; Oxonic Acid; Quality of Life; Tegafur; Zoledronic Acid

A 42-year-old female underwent surgery for cancer of the left breast (T3N2M0) in February 2003, and FEC 70, followed by CMF, was administered as adjuvant therapy. In January 2009, second-line chemotherapy with weekly paclitaxel therapy was started after multiple pleural and bone metastatic lesions had been found. Despite this treatment, she required radiation therapy for the growth of bone metastatic lesions. As paclitaxel apparently had no useful effect on the lesions, S-1 chemotherapy, given as third-line therapy starting in December 2009, was considered useful for disease control without progression demonstrated by PET evaluation.

Topics: Adult; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Drug Combinations; Female; Humans; Oxonic Acid; Pleural Neoplasms; Positron-Emission Tomography; Recurrence; Salvage Therapy; Tegafur

The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients.. A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.. At least one adverse drug reaction was encountered by 858 patients, with an overall incidence of 63.0% (858/1361). The incidence of Grade 3 or higher adverse drug reactions in a descending order was 14.7% (200/1361). In this study, the most common combination drug was trastuzumab. The overall incidence of adverse drug reactions was 63.5% (431/679 patients) in patients treated with S-1 alone, and 55.9% (66/118 patients) in patients treated with S-1 + trastuzumab.. Monotherapy with S-1 or combination therapy with S-1 + trastuzumab was well tolerated for inoperable or recurrent breast cancer patients.

Topics: Administration, Oral; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asian People; Breast Neoplasms; Drug Administration Schedule; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Incidence; Japan; Logistic Models; Middle Aged; Oxonic Acid; Product Surveillance, Postmarketing; Prospective Studies; Severity of Illness Index; Tegafur; Trastuzumab

The patient, a 58-year-old woman, underwent a partial excision of the right breast and an axillary lymph node dissection in October 2004. The histopathological findings were: solid tubular carcinoma with metastasis to 17 axillary lymph nodes; triple negative-type breast cancer. As adjuvant therapy, FEC60 was administered 6 times, followed by radiotherapy applied to the residual breast and the right supraclavicular fossa. In Novermber 2007, she noted a tumorous growth above the right clavicle. The pathological diagnosis via fine needle biopsy was adenocarcinoma. An oral antineoplastic agent was given for about 6 months, but did not alter the lymph nodes. No distant recurrence was noted during this time. In August 2008, the right supraclavicular lymph nodes were dissected. The patient has been under observation without treatment, but no signs of recurrence have been noted. It was thought that excision of the recurrent supra-clavicular lymph nodes should be considered after careful examination in some individual cases.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Biopsy, Needle; Breast Neoplasms; Clavicle; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Recurrence; Remission Induction; Tegafur

When treating advanced and metastatic breast cancer patients with chemotherapy, it is mandatory to maintain the patients quality of life while keeping an acceptable level of antitumor activity. For these purposes, oral administration of S-1, fluorinated pyrimidine, is a good choice of treatment. Conventionally, a 4-week administration followed by a 2-week rest has been the treatment of choice with S-1. However, we applied a new regimen for 16 patients with advanced and metastatic breast cancer, in which one course consisted of a 2 week-administration followed by a week of rest, repeated twice. The median age of the patients who received this treatment was 59 years old(range 46. 8-80. 6). The response rate was 31. 2%, and the median values of time to progression and overall survival were 5. 1 and 17. 9 months, respectively. One case of thrombocytopenia as an adverse event was recognized. Our new S-1 regimen is likely to show an acceptable anti-tumor effect with minimal adverse events. The fidings suggest that this new regimen is clinically applicable for advanced and metastatic breast cancer patients.

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Tegafur

We experienced 3 cases of anti-cancer drug-resistant recurrent breast cancer with liver metastasis showing significant improvement by S-1. Almost all patients maintained the full dose through the whole course of treatment, and the drug showed good tolerability. Furthermore, long-term therapeutic efficacy(more than 2 years)and QOL have been maintained for all patients. We concluded that S-1 is not only effective as a therapeutic agent, but is safe and maintains QOL.

Topics: Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Oxonic Acid; Quality of Life; Tegafur; Time Factors

Topics: Aged; Androstadienes; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Biomarkers; Biomarkers, Tumor; Breast Neoplasms; Drug Combinations; ErbB Receptors; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Neoplasm Staging; Oxonic Acid; Receptor, ErbB-2; Receptors, Estrogen; Tegafur; Trastuzumab

We report a case of breast carcinoma with repeated recurrences in the right bone. The recurrent site of the bone was treated by radiation therapy with a total of 3 7. 5 Gy irradiation, and chemotherapy with the CMF regimen. After 2 years, recurrence was suspected in the same region because there was an elevation of the NCC-ST-439 tumor marker. We carried out chemotherapy with S-1 100mg/body/day. The NCC-ST-439 value returned to within the normal range after 3 months' administration of S -1, and continued in the normal value for 20 months.

Topics: Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Remission Induction; Tegafur

We experienced 3 cases of recurrent breast cancer treated with S-1 therapy, delaying tumor progression and improving their quality of life (QOL). All the patients had been previously treated with both anthracyclines and/or taxanes prior to S-1 chemotherapy. All patients almost completed the full dose through the whole course of treatment, and the drug showed good tolerability. Long-term(more than 12 weeks)therapeutic efficacy and the patients' QOL have been maintained for all patients. No major side effects were seen. It is thought that less toxicity enabled patient 3 to undergo long-term therapy. It is especially important that one patient had therapeutic efficacy and QOL improvement from treatment with S-1 and aromatase inhibitor for over 3 years, after being treated with anthracyclines, taxanes and vinorelbine. We conclude that S-1 is effective and well tolerated in patients with metastatic breast cancer, and will accommodate a long-time progression with respect to efficacy and maintaining the patients' QOL. Further evaluation of S-1 is necessary to elucidate its clinical role in breast cancer treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

The case is a woman in her 50's. A total glandectomy was performed for her breast cancer on August 8, 1998, and subsequently chemotherapy(5'-DFUR, CMF, uracil.tegafur, CEF, and docetaxel)as well as radiation therapy and surgical resection have been performed for local recurrence. With multiple hepatic metastasis recognized in September, 2007, chemotherapy combined with S-1/paclitaxel(PTX)has been performed. In view of the side effects such as reduction in appetite and leukocyte, the dosage has been reduced as of the second course of treatment. With the disappearance of hepatic metastasis on CT, 6 courses of S-1monotherapy have been performed after completing 6 courses of chemotherapy combined with S-1/ PTX. As of March, 2009, the therapeutic effect shows that continuous CR and outpatient follow-up have been performed while maintaining QOL. Since any chemotherapy after thirdline treatment for recurrent breast cancer has not been established yet, chemotherapy combined with S-1/PTX is considered to be one of the regimens and therefore, the second and thirdphase clinical tests ahead are expected to bring better outcomes.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Paclitaxel; Recurrence; Tegafur; Tomography, X-Ray Computed

We experienced a case of anthracycline- and taxane-resistant recurrent breast cancer with multiple liver metastases and multiple bone metastases showing marked improvement by S-1. A 52-year-old woman visited our hospital because of her liver dysfunction in May 2008. She underwent a partial mastectomy preserving chest muscles in another hospital in 2000, but further details were unknown. Radiographic imaging tests revealed multiple metastases to the liver and bones in May 2008, and she was referred to our hospital for management of metastatic lesions. Tumor of the liver was diagnosed as metastases from the breast carcinoma, ER+, PgR+, HER2 (0), and histopathologically by core needle biopsy under ultrasonography. She received 4 courses of EC after 4 courses of biweekly docetaxel treatment. She showed a partial response (PR), so she was treated by the same course of treatment again. But she was diagnosed with an enlargement of liver metastases and recurrence of bone metastases by PET examination. Then the oral treatment with S-1 was started, and at the end of the second course, a significant reduction of abnormal accumulation in PET was noted. She has been quite well without any adverse effects from S-1. S-1 monotherapy was thus considered to be an effective treatment for advanced or recurrent breast cancer resistant to anthracyclines and taxanes.

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Positron-Emission Tomography; Recurrence; Salvage Therapy; Taxoids; Tegafur

We report a long-term complete response (CR) in a patient with postoperative recurrent breast cancer and bone and pleura metastases after treatment with a combination of S-1 and zoledronic acid. We administered 4 courses of tri-weekly CE (epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2) and 12 courses of weekly paclitaxel (80 mg/m2) as adjuvant chemotherapy. However, combination therapy with S-1 and zoledronic acid was started because of the development of bone and pleura metastases. S-1 was administered orally at 100 mg/day everyday for 2 weeks, followed by a 1-week rest interval as 1 course; 4 mg of zoledronic acid was injected every 4 weeks. After 3 cycles of treatment, the patient's tumor marker levels had decreased to normal values, and both the bone and pleura metastases had disappeared. A long-term complete response was obtained as a result of this combination therapy.

Topics: Biomarkers, Tumor; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Drug Combinations; Humans; Imidazoles; Oxonic Acid; Pleural Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed; Zoledronic Acid

We experienced a case of Luminal B recurrent breast cancer with liver and lymph node metastases achieving significant improvement by S-1 plus trastuzumab combination therapy. This patient was a 47-year-old woman. Trastuzumab monotherapy was administered after recurrence, but her condition grew worse. Thus, we started combination therapy of trastuzumab plus S-1. S-1 was administered orally at 100 mg/day every day for 4 weeks followed by a 1-week rest period as one course, and trastuzumab was then injected at 2 mg/kg every week. All metastases disappeared after two courses of the treatment, and no new malignant lesions appeared. In conclusion, combination therapy of S-1 plus trastuzumab could be effective treatment for maintaining good QOL in Luminal B recurrent breast cancer with lymph node and liver metastases.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Recurrence; Salvage Therapy; Tegafur; Tomography, X-Ray Computed; Trastuzumab

S-1, an oral fluoropyrimidine derivative, has been identified as an effective agent for the treatment of breast cancer. We present here a case of interstitial pneumonitis that occurred after S-1 treatment. A n 80-year-old woman was diagnosed with stage III infiltrating ductal carcinoma of the left breast and underwent a modified radical mastectomy in November 2001, followed by six courses of paclitaxel. In October 2008, metastatic disease was detected in her skeletal system. Therefore, S-1 chemotherapy was initiated (100 mg/body). Five days after starting S-1, she developed severe eruptions along with dyspnea. X-rays and CT scan showed diffuse ground glass shadow. Both her symptoms and the radiographic findings resolved dramatically after the start of high-dose corticosteroid therapy. Clinicians should be aware that S-1 has the potential to cause lung injury when it is included in chemotherapy.

Topics: Aged, 80 and over; Breast Neoplasms; Drug Combinations; Female; Humans; Lung Diseases, Interstitial; Neoplasm Metastasis; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

S-1 is an orally administered fluorinated pyrimidine with high activity in metastatic breast carcinoma (MBC) and in chemotherapy-pretreated metastatic breast carcinoma.. 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.. 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.. 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.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Capecitabine; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Retrospective Studies; Salvage Therapy; Tegafur; Treatment Outcome

We report a case of multi-drug-resistant breast cancer with liver metastases which completely responded and improved the quality of life (QOL)by S-1 monotherapy. The patient was a 53-year-old woman, who was diagnosed as breast cancer with invasive chest wall, cervical lymph node metastases, multiple bone metastases and bilateral pleural effusion[invasive ductal carcinoma, scirrhous type, ER(-), PgR(+), HER2(1+)]. After six courses of cyclophosphamide+epirubicin(CE)and weekly paclitaxel for 3 months, cervical lymph node metastasis was judged as a partial response(PR)and the bilateral pleural effusion disappeared. After chemotherapy, aromatase inhibitor (AI) was used. However, primary lesion and multiple bone metastases no change(NC). Following pass through AI+ oral anticancer drug combination chemotherapy and oral anticancer drug monotherapy, the therapy was changed to palliative, and she was referred to our hospital in January 2007. On arrival at the hospital, respiratory distress and bilateral pleural effusion had appeared, so it was an emergency admission. After removing the pleural effusion, pleurodesis was done and the symptoms disappeared. Although AI plus bisphosphonate therapy were started at hospital discharge, disease progression and fatigue appeared. In December 2007, we started S-1 monotherapy. S-1 was given orally at 80 mg/m2 for day 1-28 followed by a 2-week rest period, within a 6-week courses. Six months after treatment was started, multiple liver metastases disappeared and peritoneal effusion decreased. During the period of S-1 treatment, there were no serious adverse events, and treatment was possible without compromising QOL. This result suggested that S-1 treatment was a reasonable option for multi-drug-resistant breast cancer.

Topics: Antimetabolites, Antineoplastic; Breast Neoplasms; Carcinoma, Ductal, Breast; Drug Combinations; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur

Thirteen months following surgery, local recurrence and multiple lung metastases occurred. Hormone therapy was continued following the recurrence but was found to be ineffective, so the patient was referred to our hospital 9 months after the recurrence. Capecitabine-based chemotherapy was administered but found to be ineffective; 3 months later, the anti-cancer drug was changed to S-1. After 3 months of S-1 administration, a CT scan showed a marked reduction in sites of recurrence and metastasis, making it possible to control progression of the disease over a longer period. No critical adverse reactions were observed, suggesting that S-1 can be useful and safe for the treatment of capecitabine-resistant recurrent breast cancer.

Topics: Breast Neoplasms; Capecitabine; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

It is not clear what the optimal treatment of chemotherapy is for patients with heavily treated metastatic breast cancer (MBC). We have retrospectively examined the efficacy and safety of S-1 in patients with MBC who had been previously treated with anthracycline, taxane, and capecitabine.. Patients with MBC who had been administered S-1, an oral modulated compound containing a fluoropyrimidine derivative, between November 2001 and June 2003 at the Cancer Institute Hospital were retrospectively reviewed. S-1 at a standard dose of 50 mg/body was administered twice daily for four weeks, followed by a two-week rest period. This was repeated every six weeks until disease progression or unacceptable toxicity.. Thirty-five patients were assessed. The patients were heavily pretreated with anthracycline (100%), taxane (paclitaxel or docetaxel) (100%), capecitabine (100%), vinorelbine (71%), and mitomycin (69%). Median follow-up time of patients was 9.6 months (range, 1.2-26.6). ORR was 3% (95% confidence interval: 0-9%), and CBR was 20% (95% confidence interval: 6-33%). Time to treatment failure was 2.8 months. Overall survival was 21.4 months. Grade 1 or 2 adverse events were observed in 17% and 13%, respectively. Grade 3 events occurred as anorexia (9%), nausea (9%), vomiting (9%), diarrhea (14%), fatigue (3%), and elevation of AST/ALT (3%). No grade 3 was seen as hand-foot syndrome. Neither grade 3 nor 4 was observed in bone marrow suppression.. S-1 was fairly well tolerated, but demonstrated very limited activity in capecitabine-pretreated patients who had already been exposed to anthracycline and taxane. It was suggested that S-1 clinically exhibited cross-resistance to capecitabine.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Pleural Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Taxoids; Tegafur; Treatment Outcome

We experienced a case of triple-negative recurrent breast carcinoma achieving a significant improvement by oral S- 1, a fluoropyrimidine-class anticancer drug and zoledronic acid(ZOL), a third generation bisphosphonate(BP). / Against metastases to orbital foramen, chest wall and bone, the oral treatment with S-1 was started at 80 mg/day everyday for 4 weeks, followed by a 2-week rest interval as 1 cycle, and ZOL was injected at 4 mg every 4 weeks. After 2 cycles of treatment, the level of tumor markers and tumor sizes became reduced. Twelve cycles after the initiation of the therapy, recrudescence of the metastatic lesions was not recognized, and no other metastases were recognized in any organ. In the course of the treatment, no adverse drug reactions to S-1 occurred in the patient. For treatment of recurrent breast carcinoma, S-1 is considered to be a useful and tolerable anticancer drug, and combination treatment of S-1 and ZOL is thought to be effective.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Diphosphonates; Drug Combinations; Female; Humans; Imidazoles; Magnetic Resonance Imaging; Neoplasm Metastasis; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed; Treatment Outcome; Zoledronic Acid

We report a case of a 52-year-old female with multiple skin metastases from breast cancer who responded to S-1. She underwent surgery of her right breast in March 2000 and the left in June 2006. Multiple skin metastases were later detected. As there was no hormone sensitivity, chemotherapy was selected. We started treatment with administration of S-1 at 120mg/day(4 weeks)and trastuzumab. Thoracic CT at the end of the three courses revealed the disappearance of the multiple skin metastases. No major side effects were seen. It was concluded from these findings that S-1 could be safely and effectively administered to advanced breast cancer patients.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Immunotherapy; Middle Aged; Oxonic Acid; Skin Neoplasms; Tegafur; Tomography, X-Ray Computed; Trastuzumab

We experienced a case of inflammatory carcinoma, which has been well controlled by chemotherapy, especially, vinorelbine, S-1 and trastuzumab. A 54-year-old woman was diagnosed as inflammatory carcinoma with T4d, N3c, M0 in Stage III c. The lesion was diagnosed as invasive ductal carcinoma, scirrhous, ER(-), PgR(-), HER2(3+) by core needle biopsy, The skin lesion was diagnosed as dermal lymphatic carcinomatosis by skin biopsy. The following chemotherapy was performed: FEC(5-FU 500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2) followed by docetaxel(DOC 70 mg/m/2), every 3 weeks, each 6 times; after that, sequentially, vinorelbine (25 mg/m2)+trastuzumab (2 mg/kg every week), UFT(300 mg, daily)+cyclophosphamide (100 mg 2 weeks on, 1 week off)+trastuzumab (continued) and S-1 (120 mg/body 4 weeks on, 2 weeks off)+trastuzumab (continued). The patient has been well controlled by the chemotherapy with good QOL. Especially vinorelbine, S-1, and trastuzumab contributed to the disappearance of skin lesion.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Cyclophosphamide; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Inflammation; Middle Aged; Oxonic Acid; Skin Neoplasms; Taxoids; Tegafur; Trastuzumab; Vinblastine; Vinorelbine

A 46-year-old woman was diagnosed with complaints of bilateral breast tumor with massive ascites retention. The patient was examined as scirrhous carcinoma by lacteal gland inspection and dysplastic cell by ascites cytotechnology. We diagnosed her case to be bilateral breast cancer with peritonitis carcinomatosa, lymph node metastases and bony metastases. In addition to that, gastric metastasis was diagnosed by the result of widespread irregular gastric mucosa, which was inspected through upper gastrointestinal endoscope. The patient was treated with S-1 and paclitaxel and has achieved a remarkable response. The patient's tumor, gastric metastasis, and ascites were disappeared almost completely.

Topics: Adenocarcinoma, Scirrhous; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Peritonitis; Stomach Neoplasms; Tegafur

In November 2005, a 34-year-old female presented to our department with a bleeding tumor on her right breast. She noticed the tumor approximately two years ago but she left it untreated. An exposed tumor was observed with a diameter of approximately 8 cm located in the right breast. It was diagnosed as invasive ductal carcinoma by biopsy (ER (+), PgR (+), and HERS2: 1 +). The imaging showed multiple metastases to the bilateral lungs, right axillary lymph node, mediastinal lymph node and sternal. The diagnosis was made as right breast cancer (T4c, N3c, M1, and stage IV). The patient received 4 courses of FEC therapy and 4 courses of PTX therapy. The patient had a partial response (PR). However, tumor markers were elevated in September 2006. Thus, an administration of S-1 was initiated. The size of the tumor shown in the imaging was reduced, and the patient had a PR. Since December 2008, tumor markers have been elevated again. However, the patient has had SD in the imaging and S-1 administrations have been continued. A total of 24 courses have been performed to the present time, and the patient's conditions have not been aggravated in approximately 3 years and 5 months. She has maintained a good QOL and is being followed up on an outpatient basis. S-1 administrations can be an effective treatment for advanced breast cancer resistant to anthracycline and taxane when considering a satisfactory QOL of patients.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal; Cyclophosphamide; Drug Combinations; Epirubicin; Female; Fluorouracil; Humans; Oxonic Acid; Paclitaxel; Pentoxifylline; Quality of Life; Tegafur; Treatment Outcome

S-1 was found to be highly effective against metastatic hepatic lesions from multiple drug-resistant breast cancers, in 2 patients. The details of these cases are presented below. Case 1, a 59-year-old woman, was HER2-positive. For chemotherapy following a recurrence, trastuzumab+weekly paclitaxel and trastuzumab+vinorelbine regimens were attempted, but the hepatic metastasis worsened. On the other hand, a trastuzumab+S-1 regimen resulted in a notable reduction in the metastatic foci of the liver approximately one month after the initiation of the therapy. This effect was sustained for 5 months thereafter. Case 2 involved a 67-year-old woman with HER2-negative breast cancer. Following a recurrence, chemotherapeutic agents, such as taxane and vinorelbine, were applied, which all resulted in PD. Treatment with S-1 alone reduced the size of the hepatic metastatic lesion, as seen in case 1. Currently (14 months after the initial treatment with S-1), therapeutic efficacy has been maintained. Adverse effects were minimal and QOL was not compromised in either case. We speculate that S-1 is not only effective as a therapeutic agent but is also useful in view of safety and QOL.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Drug Combinations; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

We here describe a case of advanced breast cancer (Stage IV) in which an oral S-1+TAM therapy following a primary systemic chemo-radiotherapy has been effective in maintaining the patient's QOL. A 40-year-old woman visited our hospital because of her left breast tumor. On physical examination, the tumor had invaded to the skin adjacent to the nipple forming a skin ulcer and marked deformity of the entire breast. Also noted were swollen lymph nodes in the left armpit. Subsequently, radiographic imaging tests revealed that the tumor had metastasized to the liver and lungs, as well as the skull. Accordingly, a primary systemic chemotherapy (4 series of AC/T) was started and followed by local radiation therapy (60 Gys) immediately after completing the chemotherapy. The metastasizing lesions in the liver, lungs, and skull had markedly reduced in the size and number, and the skin ulceration had healed up by these treatments. Afterwards, she has been given TAM daily and S-1 for 4 weeks with a 2-week interval. She has been quite well without any adverse effects by S-1 and TAM, and the primary as well as metastasizing lesions remain stable with normalized tumor marker levels (NC) for nearly 3 years.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Combinations; Female; Humans; Mitoxantrone; Neoplasm Staging; Oxonic Acid; Paclitaxel; Tegafur; Time Factors; Tomography, X-Ray Computed; Topotecan

S-1, an oral fluoropyrimidine carbamate, is an active and well-tolerated agent against solid cancer. However, the clinical efficacy of S-1 in patients with metastatic breast cancer has not been determined.. We retrospectively evaluated the efficacy of S-1 and identified its adverse effects in patients with metastatic breast cancer who had failed to respond to prior chemotherapy regimens. All the patients were treated at the National Cancer Center Hospital and received S-1 twice daily at a dose of 80 mg/m(2) for 4 weeks, followed by a 2-week rest interval.. Between 2003 and 2007, 37 women with metastatic breast cancer received S-1 as a third line or greater chemotherapy regimen. All the patients had been previously treated with both anthracyclines and taxanes prior to S-1 chemotherapy. The median order of S-1 administration was as a fifth-line treatment, and 23 patients (62%) received S-1 as their final anticancer drug. One (3%) partial response and two (5%) stable diseases were observed. The median time to progression (TTP) was 84 days. Grade 2 adverse events, such as diarrhea, stomatitis and neutropenia occurred in 5 (16%), 1 (3%) and 1 (3%) patients, respectively.. S-1 was safety administered to heavily treated metastatic breast cancer patients with limited efficacy. Further evaluation of S-1 is necessary to elucidate its clinical role in breast cancer treatment.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Diarrhea; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Nausea; Oxonic Acid; Retrospective Studies; Tegafur

A resected case of squamous cell carcinoma associated with ductal carcinoma in the hemilateral breast successfully treated by FU plus cisplatin (CDDP) adjuvant therapy against recurrent metastases is reported with some discussion. A 42-year-old woman was admitted to our hospital because of right breast tumor. By physical examination, mammography, ultrasound examination and aspirated cytology, we diagnosed squamous cell carcinoma of the right breast. Before operation SCC antigen was elevated. Standard mastectomy was performed, and SCC antigen was decreased within normal range. Then, a standard regimen of chemotherapy using docetaxel with anti-hormonal therapy by LH-RH analog and tamoxifen was done as first-line adjuvant therapy. Four months after operation the SCC antigen level was elevated again, and recurrence of cancer (skin and liver metastases) was recognized. Next, we tried 5-FU/UFT plus CDDP for squamous cell carcinoma of other organs such as the esophagus. These anti-tumor drugs proved effective, and no metastasis of the skin was detected thereafter, and liver metastatic lesion was decreased in ten months. The SCC antigen level was within the normal range again. Additionally, when metastases redeveloped, TS-1 plus CDDP controlled growth of tumors in seven months. Based on the present findings,we recommend adjuvant chemotherapy by FU plus CDDP for squamous cell carcinoma of the breast.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Mastectomy; Neoplasm Invasiveness; Oxonic Acid; Skin Neoplasms; Tegafur; Uracil

We report a rare case of breast metastasis of gastric cancer in a 61-year-old female. She was diagnosed as primary gastric cancer with peritoneal dissemination and received systemic chemotherapy after distal gastrectomy for a primary lesion. A tumor developed in her right breast 4 years after the surgery, and was confirmed to be the metastasis from gastric cancer by aspiration cytology. In Japan, there are 25 reports of breast metastasis from gastric cancer. Two possible pathways from gastric lesion were lymphatic and one vascular, but the mechanism of breast metastasis has remained controversial.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Signet Ring Cell; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Middle Aged; Neoplastic Cells, Circulating; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Uracil

High-dose toremifene therapy (120 mg/day) is useful for the recurrence of receptor-positive breast cancer. However, some reports show that combination therapy of high-dose toremifene and chemotherapy exhibits additive effects. Twelve patients were given oral chemotherapy (capecitabine, 5'-DFUR+CPA, S-1) with high-dose toremifene. The overall response rate was 41.7%, in addition to 58.3% with no change beyond three months. Adverse events were restricted to headache, stomatitis and nausea. Average time to progressive (TTP) was 5.8 months. It was shown that high-dose toremifene and oral chemotherapy were useful for breast cancer recurrence without severe side effects.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Cyclophosphamide; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Floxuridine; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Quality of Life; Skin Neoplasms; Tegafur; Toremifene

We report a 60-year-old female with pulmonary metastasis from breast cancer who responded to S-1. In November 2001, she underwent surgery. In October 2005, relapse was detected. As there was no hormone sensitivity, chemotherapy was selected, and oral administration of S-1 at 120 mg/day (2 divided doses) was initiated. After the fourth course, the tumor marker level returned to the reference value. Thoracic CT at the end of the sixth course revealed the disappearance of the metastatic focus. Adverse reactions during the administration period were mild. S-1 showed potent antitumor effects and good tolerance, and it may be useful for treating metastatic/recurrent breast cancer.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mastectomy, Segmental; Middle Aged; Mucin-1; Oxonic Acid; Quality of Life; Tegafur

We report a case of advanced breast cancer (T4b, N3c, M1) achieving a significant improvement on QOL by multi-disciplinary therapy and S-1 administration. The patient was a 59-year-old woman who had ulcerative breast lump with bleeding. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma negative for estrogen receptor, progesterone receptor, and HER2/neu protein expression. The aspiration biopsy cytology was performed from skin lesion, the diagnosis was class V. She received 6 cycles of tri-weekly CEF (C: 500 mg, E: 60 mg, F: 500 mg/m2) therapy. The effect of the breast tumor was partial response, and the bleeding from the breast lump was improved. But the response from metastatic skin tumor was less satisfactory. We performed a radiation therapy (20 Gy) to metastatic skin tumor, and the lesion disappeared after the radiation therapy. Then, we tried docetaxel, but the side effect appeared. So, we started administering S-1 after docetaxel. One year later, she was estimated to be in the long stable disease. Multi-disciplinary therapy can improve a patient QOL and the clinical outcomes in Stage IV advanced breast cancer.

Topics: Biopsy, Needle; Breast Neoplasms; Drug Combinations; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

We experienced a case of recurrent breast cancer resistant to prior medications, which was treated with oral S-1, a fluoropyrimidine-class anticancer drug, and exhibited the marked shrinkage of liver metastasis. The prior treatments including anthracycline and taxane were judged not effective because of the progressive disease. Then the oral treatment with S-1 was started at 120 mg/day bid. targeting metastatic lesions of the liver. At the end of the second cycle,a significant improvement was noted with a decrease rate of 82.5%. The S-1 monotherapy was thus considered to be an effective treatment for advanced or recurrent breast cancer resistant to anthracyclines and taxanes.

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Mastectomy, Segmental; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

We had 2 patients with marked shrinkage of liver metastasis by administration of the oral fluorinated pyrimidine anticancer drug S-1 for advanced/recurrent breast cancer that was resistant to taxane and another antitumor drugs. Both patients almost completed the full dose through the whole course of treatment,and the drug showed good tolerability. S-1 was considered to possess beneficial antitumor efficacy and tolerability and to be promising as home chemotherapy for advanced/recurrent breast cancer.

Topics: Administration, Oral; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

We had 3 patients with recurrent/advanced breast cancer in whom a notable reduction in the size of the targeted tumors was seen following administration of S-1 (TS-1), a new oral pyrimidine fluoride anticancer drug. All of the patients had received taxane and/or anthracycline anticancer drugs as prior therapy; however, they were judged to be non-responsive to the drugs. The size of the targeted tumor decreased to 55.7% after 3 courses of the therapy in Patient 1. The tumor disappeared at completion of the third course in Patient 2, although the therapy was temporarily suspended during the second course due to adverse drug reactions, and the therapy was then resumed after 2-week drug withdrawal. Patient 3 was able to undergo long-term therapy, consisting of 8 courses for 11 months, and the size of the tumor reduced to 58.1%. No serious adverse drug reactions to S-1 occurred in our 3 patients. It is thought that less toxicity enabled Patient 3 to undergo long-term therapy. We consider S-1 to be a useful anticancer drug for treatment of taxane and/or anthracycline resistant recurrent breast cancer.

Topics: Aged; Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Lymph Node Excision; Lymph Nodes; Mastectomy, Segmental; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

In vivo experiments were performed on breast cancer xenografts to examine whether the combination therapy with S-1, an oral dihydrouracil dehydrogenase (DPD) inhibitory fluoropyrimidine, plus docetaxel functions as an additive/synergistic modulator in tumor growth. The human breast cancer xenograft, MDA-MB-435SHM, was inoculated into SCID female mice. The tumor growth and thymidylate synthase (TS)/DPD activity of tumors treated with the agents were investigated. The T/C value (relative mean tumor weight of the treated group/relative tumor weight of the control group) of the group treated with docetaxel, S-1 and combination therapy were 45.3, 63.1 and 29.8%, respectively; suggesting the positive antitumor effects of the combination therapy in particular. In addition, significant down-regulation of DPD activity was also observed in the tumors treated with S-1, docetaxel and their combination. Down-regulation of the DPD activity of the tumors is also considered to be correlated with the antitumor effect of the treated groups, suggesting its influence on the synergistic effect of the combination therapy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dihydrouracil Dehydrogenase (NAD+); Docetaxel; Drug Combinations; Drug Synergism; Female; Humans; Mice; Mice, SCID; Oxonic Acid; Taxoids; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

We experienced a case of multi-drug resistant recurrent breast cancer with multiple bone metastases achieving a significant improvement by TS-1 and trastuzumab. The prior treatments including taxane or vinorelbine and trastuzumab were changed in the regimen to TS-1 and trastuzumab because of the progressive disease. TS-1 was administered orally at 100 mg/day everyday for 2 weeks, followed by a 1-week rest interval as 1 cycle, and trastuzumab was injected at 2 mg/kg/week for 4 weeks, followed by a 1-week rest interval as 1 cycle. After 3 cycles of the treatment, the level of tumor markers and tumor sizes of bone metastases became reduced. In conclusion, the combination treatment of TS-1 and trastuzumab is thought to be effective for multi-drug resistant recurrent breast cancer.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Mastectomy, Segmental; Middle Aged; Oxonic Acid; Receptor, ErbB-2; Tegafur; Trastuzumab

A patient with lung metastasis of breast cancer was reported. The patient underwent surgery in December, 1999. Her breast cancer then recurred in December, 2000. After treatment failure with anthracycline and taxane antitumor drugs,she participated in a phase II study of S-1, a fluorinated pyrimidine anticancer drug, which was given orally at 80 mg/m2/day (2 doses). After completion of 4 courses of treatment,the target lesions of the lung metastasis markedly shrunk by 47.5% as compared with the pretreatment. Because salvage therapy with S-1 alone showed good antitumor efficacy and beneficial tolerability when the standard dosage was maintained, it was considered that this home therapy was effective for advanced/recurrent breast cancer that was resistant to anthracycline and taxane antitumor drugs.

Topics: Administration, Oral; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Salvage Therapy; Taxoids; Tegafur

To evaluate the antitumor and antimetastatic efficacy of oral fluoropyrimidines, alone and combined with taxane on human breast cancer xenografts model, we developed a breast cancer model that spontaneously metastasizes to the lung by orthotopic implantation of MDA-MB-435S-HM tumors into the mammary fat pad (mfp) of SCID mice. The activity of the 5-fluorouracil (5-FU)-degrading enzyme dihydropyrimidine dehydrogenase (DPD) was significantly higher in the metastatic tumors than in the primary tumors. Based on this enzymatic characteristic of pulmonary metastases of breast cancer in regard to 5-FU metabolism, we investigated the antitumor activity of two types of oral 5-FU prodrugs, with and without paclitaxel, on both orthotopically implanted breast tumors and metastatic lung tumors in mice. The drugs and doses used were: S-1, a new oral DPD-inhibiting fluoropyrimidine (DIF) 8.3 mg/kg/day, capecitabine 360 mg/kg/day as a non-DIF, and paclitaxel 50 mg/kg, all of which display minimal toxicity in mice. In the primary tumors, paclitaxel and S-1 displayed a significant antitumor activity, with 57 and 41%, respectively inhibition of tumor growth (p < 0.01), but capecitabine had no effect. When S-1 and paclitaxel were combined, they synergistically caused tumor regression (tumor growth inhibition ratio 94%, p < 0.01) in mice compared to capecitabine plus paclitaxel, without any toxicity. In the pulmonary metastasis model, paclitaxel, and both S-1 alone and combined with paclitaxel, but not capecitabine alone or combined with paclitaxel, diaplayed almost complete antimetastatic activity. These results strongly suggest that combination of S-1, as a DIF with taxanes will show a potent high antitumor and antimetastatic effect on refractory human breast cancers, especially those expressing strong DPD activity.

Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Disease Models, Animal; Drug Combinations; Female; Mice; Mice, SCID; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Pyridines; Tegafur; Transplantation, Heterologous