s-1-(combination) and Carcinoma--Ductal--Breast

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

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

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

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

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