Shigenori Kadowaki

Aichi Cancer Center, Ōsaka, Ōsaka, Japan

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Publications (12)23.81 Total impact

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    ABSTRACT: Adding oxaliplatin to fluorouracil-based chemotherapy can improve the survival of patients with stage III colorectal cancer by approximately 20 %. Reportedly, cancer patients are much more likely to prefer chemotherapy than medical professionals, although there is only a very small chance of achieving benefits from treatment. However, chronic neurotoxicity may be long lasting after the administration of oxaliplatin-based chemotherapy. This study aimed to evaluate potential side effects and differences in attitude between colorectal cancer patients and medical staff regarding the risk-benefit trade-offs of chemotherapy. Relapse-free colorectal cancer patients who received adjuvant chemotherapy, doctors, and nurses were surveyed using a questionnaire regarding the side effects of chemotherapy and hypothetical clinical scenarios to quantify gains in the risk of relapse that were deemed necessary to make chemotherapy worthwhile. Responses were obtained from 147 patients, 54 doctors, and 84 nurses. Of these, 39 % of patients and 85 % of doctors replied that moderate side effects of adjuvant chemotherapy were worthwhile to achieve an absolute gain in the risk of relapse of 10 % from a baseline of 40 %. More severe side effects, as reported by colorectal cancer patients, were not associated with the larger gains necessary to make treatment worthwhile. Seven percent of patients treated with oxaliplatin, 40 % of doctors, and 43 % of nurses replied that side effects associated with oxaliplatin-based chemotherapy were severe. Doctors should consider potential heterogeneity in side effects and attitudes regarding the risk-benefit balance of adjuvant chemotherapy, and that patient perspectives should enhance shared decision-making.
    International Journal of Clinical Oncology 11/2014; · 2.17 Impact Factor
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    ABSTRACT: Here, we report a patient with gastric adenosquamous carcinoma (ASC) with human epidermal growth factor receptor-2 (HER2) overexpression who was successfully treated with trastuzumab-based chemotherapy. The patient was a 66-year-old man preoperatively diagnosed with gastric adenocarcinoma with no evidence of distant metastases. On histopathological examination, the curatively resected tumor was identified as ASC with mixed adenocarcinoma and squamous cell carcinoma components. Multiple liver metastases developed 2.5 months after surgery. Because immunohistochemical staining for HER2 was strong in both components, combination chemotherapy with capecitabine, cisplatin, and trastuzumab was initiated. A partial response was confirmed after 6 treatment cycles and PET and CT scans performed after 13 cycles revealed disease resolution with no uptake in the metastatic lesions. No evidence of disease progression has been observed 16 months after initial chemotherapy. This report suggests the potential utility of trastuzumab-based chemotherapy for HER2-positive gastric ASC.
    Case Reports in Oncology 01/2014; 7(1):210-6.
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    ABSTRACT: The prognostic and predictive values of carbohydrate antigen 19-9 (CA19-9) levels in metastatic colorectal cancer (mCRC) remain unclear. We reviewed all mCRC patients at a single institution to evaluate the relationship between CA19-9 levels and survival. Two hundred and fifty-two patients underwent first-line chemotherapy using oxaliplatin-based regimens between April 2005 and December 2009. The relationship between baseline CA19-9 levels and survival was analyzed. Moreover, we evaluated the relationship between baseline CA19-9 levels and clinicopathological factors. One hundred and fifty patients had elevated baseline CA19-9 levels (elevated group), and 79 patients had normal baseline CA19-9 (normal group) levels. Both KRAS and BRAF mutation rates were higher in the elevated group than in the normal group. Elevated CA19-9 level was a poor prognostic factor compared with normal CA19-9 levels (P = 0.0021). In the elevated group, the median survival time with bevacizumab was significantly longer with bevacizumab than without it (median OS, 27.8 vs. 15.3 months, P = 0.0019). However, the median survival time was not different with or without bevacizumab in the normal group (median OS, 36.5 vs. 38.0 months, P = 0.9515). Our results suggest that baseline CA19-9 level is an independent prognostic factor in mCRC patients, and it correlated with the KRAS/BRAF mutation status. Bevacizumab exhibits clinical activity only for high CA19-9 levels in mCRC.
    Cancer Chemotherapy and Pharmacology 12/2013; · 2.80 Impact Factor
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    ABSTRACT: The long-term outcomes of advanced gastric cancer (AGC) patients treated with S-1 plus cisplatin (SP) combination chemotherapy remain unclear. Therefore, we sought to evaluate these outcomes to identify the prognostic factors affecting patient survival. We retrospectively analyzed 153 AGC patients treated with SP at a single institution between January 2005 and July 2011. Median overall survival (OS) was 15.0 months [95 % confidence interval (CI), 12.5-17.9 months]. Three independent prognostic factors affecting poor survival were identified: performance status (PS) ≥ 1 [hazard ratio (HR) = 2.39, 95 % CI, 1.58-3.62); >1 metastatic site (HR = 1.57, 95 % CI, 1.10-2.26], and elevated alkaline phosphatase levels (HR = 1.70, 95 % CI, 1.16-2.49). A simple prognostic index was generated using three risk groups: good (no risk factor), moderate (one or two risk factors), and poor (three risk factors). The median OS for good-, moderate-, and poor-risk groups was 28.6, 14.8, and 7.3 months, respectively (log-rank test; P < 0.0001). Among the twelve 3-year survivors, 9 (75 %) had a PS of 0 and 8 (67 %) had only one metastatic site. Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.
    International Journal of Clinical Oncology 09/2013; · 2.17 Impact Factor
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    ABSTRACT: Combination of docetaxel, cisplatin and 5-fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We conducted a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (TNM-6(th) ) were eligible. Chemotherapy consisted of intravenous docetaxel (70-75 mg/m(2) ) and cisplatin (70-75 mg/m(2) ) on day 1, and continuous infusion of fluorouracil (750 mg/m(2) /day) on days 1 to 5. Antibiotic prophylaxis on days 5 to 15 was mandatory. This regimen was repeated every 3 weeks with a maximum of 3 cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was performed. Primary endpoint was the completion rate of protocol treatment. Forty-two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty-one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment-related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2-year progression-free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This article is protected by copyright. All rights reserved.
    Cancer Science 08/2013; · 3.53 Impact Factor
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    ABSTRACT: Carcinoma ex pleomorphic adenoma (CXPA) of the salivary glands has often a salivary duct carcinoma (SDC) component, which resembles ductal carcinoma of the breast and frequently overexpresses human epidermal growth factor receptor-2 (HER2). We report a case of metastatic CXPA with SDC component who was treated with trastuzumab-based chemotherapy and has had a durable complete response. A 74-year-old man was diagnosed with CXPA of the right parotid gland. The resected tumor was histologically diagnosed as CXPA with a predominant SDC component that showed strong positivity for HER2 protein and HER2 gene amplification. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with paclitaxel and trastuzumab was initiated. A complete response was confirmed after 7 treatment cycles, and no evidence of disease progression has been observed after 13 months of initiation of therapy. This report suggests a potential utility of trastuzumab-based chemotherapy for HER2-positive CXPA.
    Case Reports in Oncology 01/2013; 6(3):450-5.
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    ABSTRACT: OBJECTIVE: Metastatic colorectal cancer with KRAS codon 12 or 13 mutations is not currently treated with anti-epidermal growth factor antibodies. A recent retrospective study in Western countries raised the possibility that KRAS p.G13D mutation may not be absolutely predictive of non-response compared with other KRAS mutations from the findings of longer overall survival and progression-free survival following cetuximab treatment. We retrospectively investigated the relationship between KRAS status and cetuximab efficacy among Japanese patients. METHODS: Data of 109 patients from nine institutions in Japan were retrospectively analysed. All patients were refractory or intolerant to fluoropyrimidine, oxaliplatin and irinotecan, and they were treated with a cetuximab + irinotecan regimen. The response rate, disease control rate, progression-free survival and overall survival were compared according to KRAS status. RESULTS: Overall, 76 (70%), 7 (6%) and 26 (24%) patients had KRAS wild-type, KRAS p.G13D and other KRAS mutations. Their various parameters were as follows: response rate: 30% (23/76), 14% (1/7) and 0% (0/26); disease control rate: 71% (54/76), 71% (5/7) and 54% (14/26); median progression-free survival: 4.6 months (95% confidence interval, 2.8-6.3), 4.1 months (0-9.9) and 2.1 months (1.5-2.8); and median overall survival: 11.2 months (6.4-16.0), 8.5 months (5.3-11.8) and 6.8 months (4.1-9.6), respectively. CONCLUSIONS: Although no statistically significant difference in progression-free survival or overall survival was observed between KRAS p.G13D-mutant and other mutant tumours, the disease control rate was higher in KRAS p.G13D-mutant patients and a partial response was observed in one such patient. Our study suggested that cetuximab showed some activity in KRAS p.G13D-mutant colorectal cancer patients. Further research is warranted.
    Japanese Journal of Clinical Oncology 10/2012; · 1.75 Impact Factor
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    ABSTRACT: It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy. We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy. In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1 months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4 months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8 months, and the median overall survival (OS) was 12.2 months. Compared with patients with an RFI of <6 months (n = 25), patients with an RFI of ≥6 months (n = 27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2 months, respectively), and longer overall survival (7.3 vs. 16.6 months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6 months was still significantly associated with PFS and OS. S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6 months.
    Gastric Cancer 10/2011; 15(3):245-51. · 4.83 Impact Factor
  • European Journal of Cancer 09/2011; 47. · 4.82 Impact Factor
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    ABSTRACT: Cetuximab, an anti-EGFR human/mouse chimeric antibody, has just been approved in Japan for patients with EGFR positive unresectable or recurrent colorectal cancer, as monotherapy or in combination with irinotecan. We reported two cases of unresectable or recurrent colorectal cancer effectively treated by cetuximab after the progression of the prior chemotherapy. Case 1: A51-year-old male suffered from sigmoid colon cancer with synchronous liver metastases. He received cetuximab plus irinotecan combination therapy in the third-line setting. Amonth after the initiation of the chemotherapy, abdominal CT showed tumor shrinkage of liver metastases. Case 2: A57-year-old female suffered from sigmoid colon cancer with metachronous liver, ovarian metastases, ascites and pleural effusion. Her performance status(PS)according to ECOG performance scale was 1, and she complained of dyspnea on exertion. She received cetuximab monotherapy in the fourth-line setting. Five weeks after initiation of chemotherapy, her chest, abdominal and pelvic CT showed tumor shrinkage of the liver metastases and the reduction of both ascites and pleural effusion, together with resolution of her dyspnea on exertion. Before cetuximab administration, we investigated KRAS status on cancer tissue previously resected in the above 2 cases, which showed KRAS wild-type. Cetuximab could be effective for KRAS wild-type colorectal cancer, as well as the previous reports from Western countries.
    Gan to kagaku ryoho. Cancer & chemotherapy 07/2009; 36(6):1003-6.
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    ABSTRACT: Prognosis in patients with recurrent or metastatic squamous cell carcinoma of the head and neck is poor, and systemic chemotherapy has an only modest impact on the outcome. Chemotherapy with cisplatin plus 5-FU (PF) is widely used, but the standard dosage, PF (100/1000; cisplatin 100 mg/m(2) day 1 and 5-FU 1000 mg/m(2)/24 h by continuous intravenous infusion on days 1 through 4), is relatively toxic for palliative use, and PF (80/800; cisplatin 80 mg/m(2) day 1 and 5-FU 800 mg/m(2)/24 h by continuous intravenous infusion on days 1 through 5) is more commonly used in Japan, albeit without clear comparative data. We retrospectively analyzed the efficacy and safety of this regimen in our institution. Thirty of 43 patients with recurrent or metastatic head and neck cancer treated with PF in our institution between 2001 and 2006 were analyzed. Entry criteria included histologically proven squamous cell carcinoma and recurrent or metastatic disease. The most common chemotherapy-related Grade 3 or 4 toxicities were nausea (16.6%), anorexia (40%), stomatitis (6.6%) and leukopenia (10%), all of which were manageable. Complete response was achieved in one patient and partial response in eight, giving an overall response rate of 30%. Median progression-free survival was 3.0 months. Estimated 2-year survival rate was 16.7% and median overall survival was 9.8 months. Of the 30 patients, 5 (16.7%) survived more than 2 years, all of whom had primary oropharyngeal cancer. In this retrospective analysis, chemotherapy with PF (80/800) for recurrent or metastatic head and neck cancer appeared to have equal efficacy and better safety than PF (100/1000).
    Japanese Journal of Clinical Oncology 03/2009; 39(4):225-30. · 1.75 Impact Factor
  • Shigenori Kadowaki, Makoto Tahara, Nagahiro Saijo
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    ABSTRACT: With the development of the medical oncology, the progress of the diagnosis and the treatment for cancer patients have provided the improvement of overall survival rates. Furthermore, the importance of the palliative care, which give the relief of the pain and maintain or improve quality of life in cancer patients, has become to be recognized recently. Because the palliative care aims to provide the cancer patients and families with the relief of "total pain", which means the complex etiology of pain, including its physical, emotional, social, economic, and spiritual components, it has been adapted not only at the terminally period but also at the beginning of the cancer treatment. Therefore, an interdisciplinary collaboration with a variety of experts is required for palliative care. Although there is a lot of problem to be solved for palliative care in Japan, each expert should investigate his own speciality but also collaborate with another.
    Nippon rinsho. Japanese journal of clinical medicine 02/2007; 65(1):5-10.