Toi M.,Kyoto University |
Iwata H.,Aichi Cancer Center Hospital |
Yamanaka T.,Institute for Clinical Research |
Masuda N.,Osaka National Hospital |
And 8 more authors.
Cancer | Year: 2010
BACKGROUND: The 21-gene signature has been intensively studied and incorporated into major guidelines for treatment decision in early breast caner. However, it remains to be examined whether this system is applicable to Asian populations. METHODS: The authors collected 325 tumor tissues from estrogen receptor (ER)-positive primary breast cancer patients who had undergone surgery and were treated with tamoxifen between 1992 and 1998. The tissues were analyzed for the 21-gene signature, and the patients were classified into groups of low, intermediate, or high risk based on the Recurrence Score. RESULTS: A total of 280 patients were eligible, with adequate reverse transcription polymerase chain reaction profiles for the Recurrence Score. Of those, 200 and 80 patients had lymph nodenegative and lymph node-positive disease, respectively. The proportions of lymph node-negative patients categorized as being at low, intermediate, or high risk were 48%, 20%, and 33%, respectively. In lymph node-negative patients, the Kaplan-Meier estimates of the distant recurrence rate at 10 years were 3.3% (95% confidence interval [95% CI], 1.1-10.0%), 0%, and 24.8% (95% CI, 15.7-37.8%) for those in the low-risk, intermediate-risk, and high-risk groups, respectively. The risk of distant recurrence in the low-risk group was significantly lower than that in the highrisk group when the entire Kaplan-Meier plots were compared (P < .001, log-rank test). There was a significant difference for overall survival between the low-risk and the high-risk groups (P = .008, log-rank test). CONCLUSIONS: This is the first report to show that the 21-gene signature has value in providing prognostic information in Asian populations with ER-positive, lymph node-negative breast cancer. © 2010 American Cancer Society.
Kurokawa Y.,Osaka National Hospital |
Sasako M.,Hyogo College of Medicine |
Sano T.,Cancer Institute Ariake Hospital |
Shibata T.,Clinical Data |
And 4 more authors.
British Journal of Surgery | Year: 2011
Background: Extended gastrectomy with para-aortic nodal dissection (PAND) or thorough dissection of mediastinal nodes using a left thoracoabdominal (LTA) approach is an alternative to D2 lymphadenectomy, with variable postoperative results. Methods: Two randomized controlled trials have been conducted to compare D2 lymphadenectomy alone (263 patients) versus D2 lymphadenectomy plus PAND (260), and the abdominal-transhiatal (TH) approach (82) versus the LTA approach (85), in patients with gastric cancer. Prospectively registered secondary endpoints bodyweight, symptom scores and respiratory function were evaluated in the present study. Results: Bodyweight was comparable after D2 and D2 plus PAND, but higher after TH than after LTA procedures at 1 and 3 years. At 1- and 3-year follow-up symptom scores were comparable between D2 and D2 plus PAND. A LTA approach resulted in significantly worse scores than a TH approach in terms of meal volume, return to work, incisional pain and dyspnoea up to 1 year. The decrease in vital capacity was significantly greater after LTA than TH procedures up to 6 months. Conclusion: Bodyweight and postoperative symptoms were not affected by adding PAND to a D2 procedure. A LTA approach aggravated weight loss, symptoms and respiratory functions compared with a TH approach. Registration numbers: NCT00149279, NCT00149266 (). Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Niho S.,National Cancer Center Hospital East |
Kunitoh H.,National Cancer Center Hospital |
Nokihara H.,National Cancer Center Hospital |
Horai T.,Cancer Institute Hospital |
And 18 more authors.
Lung Cancer | Year: 2012
Purpose: This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safety of first-line carboplatin-paclitaxel (CP) alone with bevacizumab-CP in Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Methods: Chemonaïve patients with stage IIIB, IV or recurrent non-squamous NSCLC were eligible for participation. Patients were randomly assigned in a 2:1 ratio to receive bevacizumab-CP or CP alone. Chemotherapy was repeated for up to 6 cycles or until disease progression or unacceptable toxicity. Bevacizumab recipients who completed ≥3 cycles of chemotherapy could continue bevacizumab as monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Results: After confirming the tolerability of bevacizumab-CP in a small number of patients, 180 patients were recruited, of whom 121 were assigned to bevacizumab-CP and 59 to CP alone. Hazard ratio (HR) for PFS was 0.61 with bevacizumab-CP versus CP alone (p= 0.0090; median 6.9 versus 5.9 months). Objective response rate was significantly higher with bevacizumab-CP than with CP alone (60.7% versus 31.0%; p= 0.0013). Median overall survival was >22 months in both treatment groups (HR 0.99; p= 0.9526). No new safety signals were detected. Conclusion: Study JO19907 met its primary endpoint, demonstrating that the addition of bevacizumab to first-line CP significantly improves PFS in Japanese patients with advanced non-squamous NSCLC. This prolonged PFS by bevacizumab did not translate into OS benefit with the extremely longer underlying survival compared to historical data. No new safety signals were identified in this population. (Japan Pharmaceutical Information Center [JAPIC] registration number: CTI-060338). © 2011 Elsevier Ireland Ltd.
Taira N.,Okayama University |
Shimozuma K.,Ritsumeikan University |
Shiroiwa T.,Ritsumeikan University |
Ohsumi S.,National Shikoku Cancer Center |
And 7 more authors.
Breast Cancer Research and Treatment | Year: 2011
Provision of social support and rehabilitation for patients with physical, mental, and functional problems after cancer treatment is important for long-term health-related quality of life (HRQOL). Effective use of human and financial healthcare resources requires identification of patients requiring rehabilitation. The objectives of the current study were to clarify the patterns of physical and psychosocial recovery over time, to evaluate the associations among baseline variables, treatment-related factors and HRQOL at 6 months, 1, and 2 years after breast cancer surgery, and to identify the significant factors predicting HRQOL at each point. A multicenter longitudinal study was performed to evaluate physical conditions, anxiety, depression, and HRQOL at 1 month (baseline), 6 months, 1, and 2 years after surgery in 196 patients (mean age: 53.3 years old) with early breast cancer and no postoperative recurrence. Physical conditions were evaluated using a patient-reported symptom checklist. HRQOL was rated using the functional assessment of cancer treatment scale-general (FACT-G) and the breast cancer subscale (FACT-B). Anxiety and depression were rated using the hospital anxiety and depression scale (HADS). More than 50% of patients had local problems of "tightness", "arm weakness." and "arm lymphedema", and systemic problems of "reduced energy, fatigue, and general weakness" postoperatively. The HRQOL score significantly improved 1 year after surgery, and scores for physical, emotional and functional well-being also increased with time, whereas the score for social well-being was the highest at baseline and decreased with time. Depression and anxiety significantly improved with time. Concomitant disease, marital status, and the presence of a partner, anxiety and depression at baseline, pathological lymph node involvement, and adjuvant intravenous chemotherapy were significant factors predicting FACT-G scores at 6 months, 1, and 2 years after surgery. Depression at baseline was a strong predictor of HRQOL up to 2 years after surgery. These results suggest that physical rehabilitation is required for tightness and lymphedema to improve long-term postoperative physical function. A further study of psychosocial interventions is required to improve depression and social well-being after breast cancer surgery. © 2011 Springer Science+Business Media, LLC.
Yamamoto N.,Shizuoka Cancer Center |
Muraakmi H.,Shizuoka Cancer Center |
Nishina T.,National Shikoku Cancer Center |
Hirashima T.,Osaka Prefectural Medical Center for Respiratory and Allergic Diseases |
And 8 more authors.
Annals of Oncology | Year: 2013
Background: Tivantinib (formerly ARQ 197) is a selective inhibitor of c-Met mainly metabolized by CYP2C19. CYP2C19 is known for genetic polymorphisms, and ~20% of Asians are poor metabolizers (PMs), while others are extensive metabolizers (EMs). In this study, we examined the safety, pharmacokinetics (PK), and preliminary efficacy of tivantinib as a single agent to determine recommended phase II doses (RPIIDs). Patients and methods: Forty-seven patients (EMs, 33; PMs, 14) with solid tumors were orally treated with tivantinib, from 70 to 360 mg bid in a 3 + 3 dose-escalation scheme. EMs and PMs were separately enrolled at the doses >120 mg bid. Results: Tivantinib was well tolerated up to 360 mg bid for EMs and 240 mg bid for PMs. Neutropenia, leukopenia, anemia, fatigue, and anorexia were the frequent adverse events related to tivantinib and were commonly observed in both EMs and PMs. PMs had 1.9-fold higher AUC0-12 compared with EMs at 240 mg bid. Regardless of CYP2C19 phenotype, Gr.4 neutropenia occurred in patients with relatively high exposure to tivantinib. A confirmed partial response was achieved in two non-small-cell lung cancer (NSCLC) patients. Conclusion: Two different settings of RPIIDs, 360 mg bid for EMs and 240 mg bid for PMs, were determined. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.