Mitsudomi T.,Aichi Cancer Center Hospital
Japanese Journal of Clinical Oncology | Year: 2010
Recent progress in molecular biology has shown that cancer cells acquire common phenotypes such as self-sufficiency of growth signals, resistance to anti-proliferative and apoptotic signals through the accumulation of genetic and epigenetic changes. Recently developed anticancer drugs target these molecular mechanisms and good results have been reported for various cancer types. In lung cancer, tyrosine kinase inhibitors specific for the epidermal growth factor receptor such as gefitinib and erlotinib have changed clinical practice dramatically. About half of the Japanese patients with lung cancers harbor an activating mutation of the epidermal growth factor receptor gene and they are very sensitive to epidermal growth factor receptor tyrosine kinase inhibitors. Progression-free survival of such patients is ~ months when treated with gefitinib, whereas the survival for those treated with platinum doublet therapy is ~6 months. Target therapies against echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein or a mutated ERBB2 (v-ERB-B avian erythroblastic leukemia viral oncogene homologue 2) present in ~5% and ~3% of the Japanese patients with adenocarcinomas, respectively, are currently under development. Addition of an anti-epidermal growth factor receptor antibody, cetuximab, or anti-vascular endothelial growth factor antibody, bevacizumab, to platinum doublet therapy significantly but modestly prolonged the survival in recent clinical trials. However, clinical development of small molecule multi-kinase inhibitors including those targeting vascular endothelial growth factor receptors, such as vandetanib, sunitinib and sorafenib, has not been very successful. Through these collaborations among clinicians, basic researchers and pharmaceutical companies, it should be possible to individualize lung cancer treatment to turn this fatal disease into a chronic disorder and, eventually, to cure it. © The Author (2009). Published by Oxford University Press.
Mitsudomi T.,Kinki University |
Suda K.,Kyushu University |
Yatabe Y.,Aichi Cancer Center Hospital
Nature Reviews Clinical Oncology | Year: 2013
The discovery in 2004 of activating mutations in the EGFR gene opened the era of personalized medicine in thoracic oncology. Treatment with drugs that target EGFR typically results in dramatic tumour response compared with conventional chemotherapy in patients with non-small-cell lung cancer. Subsequently, newer driver oncogenes such as ALK, ROS1 and RET have been discovered. Nevertheless, surgery has become safer and less invasive in the past 10-15 years. In the era of personalized medicine, thoracic surgeons have to think about their evolving roles. In this article, we discuss four topics relevant to this issue. Firstly, the value of surgical specimens as opposed to biopsy specimens for further understanding tumour biology is discussed. Secondly, extended indication of surgery in the era of targeted therapy is considered. Thirdly, in clinical trials that examine neoadjuvant therapy in patients selected by appropriate biomarkers, the important role of surgeons is highlighted. Finally, the possibility of personalizing the surgical procedure itself according to lung cancer subtypes defined by biomarkers is reviewed. ©2013 Macmillan Publishers Limited. All rights reserved.
Tajika M.,Aichi Cancer Center Hospital
World journal of gastroenterology : WJG | Year: 2012
To evaluate the efficacy and safety of adjunctive mosapride citrate for bowel preparation before colonoscopy. We conducted a randomized, double-blind, placebo-controlled study with mosapride in addition to polyethylene glycol (PEG)-electrolyte solution. Of 250 patients undergoing colonoscopy, 124 were randomized to receive 2 L PEG plus 15 mg of mosapride citrate (mosapride group), and 126 received 2 L PEG plus placebo (placebo group). Patients completed a questionnaire reporting the acceptability and tolerability of the bowel preparation process. The efficacy of bowel preparation was assessed by colonoscopists using a 5-point scale based on Aronchick's criteria. The primary end point was optimal bowel preparation rates (scores of excellent/good/fair vs poor/inadequate). A total of 249 patients were included in the analysis. In the mosapride group, optimal bowel preparation rates were significantly higher in the left colon compared with the placebo group (78.2% vs 65.6%, P < 0.05), but not in the right colon (76.5% vs 66.4%, P = 0.08). After excluding patients with severe constipation, there was a significant difference in bowel preparation in both the left and right colon (82.4% vs 66.7%, 80.8% vs 67.5%, P < 0.05, P < 0.01). The incidence of adverse events was similar in both groups. Among the subgroup who had previous colonoscopy experience, a significantly higher number of patients in the mosapride group felt that the current preparation was easier compared with patients in the placebo group (34/72 patients vs 24/74 patients, P < 0.05). Mosapride citrate may be an effective and safe adjunct to PEG-electrolyte solution that leads to improved quality of bowel preparation, especially in patients without severe constipation.
Iwata H.,Aichi Cancer Center Hospital
Breast Cancer | Year: 2012
Current Japanese and American guidelines for the surveillance of patients diagnosed with early stage breast cancer recommend regular follow-up including mammography, history, and physical examination; however, additional routine laboratory and imaging studies are not recommended because there is no evidence of improved clinical outcomes associated with the early detection of distant metastasis. Metastatic breast cancer (MBC) remains a largely incurable disease. The goals of treatment for MBC are to maintain quality of life and prolong survival. However, despite the emergence of new concepts including oligometastases, cancer stem cells, and the development of individualized therapies, clinical management and treatment guidelines remain largely unchanged. The future prospects for personalized management strategies for patients with MBC are described in this review. © 2011 The Japanese Breast Cancer Society.
Iwata H.,Aichi Cancer Center Hospital
Breast Cancer | Year: 2011
Patients with resectable, nonmetastatic (stage I-IIIA) breast cancer usually receive adjuvant (postoperative) systemic therapy to control micrometastasis and prevent recurrence. Neoadjuvant (preoperative) chemotherapy is a standard treatment for resectable breast cancer, potentially enabling patients to undergo partial dissection. However, it has been reported that neoadjuvant chemotherapy has a limited effect in patients with hormone receptor-positive disease in terms of pathologic complete response rate, and in elderly patients there may be safety concerns. Furthermore, the appropriateness of chemotherapy for luminal early breast cancer [defined as hormone receptor-positive and human epidermal growth factor receptor-2 (HER2)-negative tumors] is an important clinical issue. We determine the need for chemotherapy in postmenopausal patients with hormone receptor-positive, HER2-negative, lymph node-negative early breast cancer according to clinicopathologic factors, including multigene signature. The National Surgical Adjuvant Study of Breast Cancer (N-SAS-BC06) New primary Endocrine-therapy Origination Study (NEOS) is a randomized phase III trial conducted in Japanese centers. It is evaluating adjuvant endocrine therapy, with or without chemotherapy, in patients with postmenopausal breast cancer that has responded to neoadjuvant letrozole. The aims of this trial are to: define patients who might not require chemotherapy by using their response to neoadjuvant endocrine therapy; analyze the relationship between neoadjuvant endocrine therapy and long-term prognosis; and analyze the correlation between clinical and pathologic response to neoadjuvant hormonal therapy with additional postoperative chemotherapy. We hope that the results of this trial will lead to the development of a new clinical strategy of pre- and postsurgical treatment for luminal breast cancer. © 2010 The Japanese Breast Cancer Society.