title: Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. t.shigekawa@gmail.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigekawa
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. aosaki@saitama-med.ac.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Osaki
authors.affiliation: Department of Radiation Oncology, Saitama Medical University International Medical Center, Saitama, Japan. h-sekine@jikei.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sekine
authors.affiliation: Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan. nobus@niigata-cc.jp.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan. kanba@niigata-cc.jp.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Kanbayashi
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. h_sano@saitama-med.ac.jp.|Department of Surgery, Sasaki Memorial Hospital, Saitama, Japan. h_sano@saitama-med.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sano
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. htake@saitama-med.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. syueda2000@yahoo.co.jp.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. nakamiya@saitama-med.ac.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakamiya
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. nikoniko0215@hotmail.com.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Sugitani
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. michikos612@gmail.com.
authors.forename: Michiko
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. h0113@saitama-med.ac.jp.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. eiko1126@saitama-med.ac.jp.
authors.forename: Eiko
authors.initials: E
authors.lastname: Hirokawa
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. ozokichilalakichi@yahoo.co.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1298, Japan. tsaeki@saitama-med.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid