Misawa City Hospital
Misawa City Hospital
Yamada Y.,National Cancer Center Hospital |
Takahari D.,Aichi Cancer Center Hospital |
Matsumoto H.,Komagome Hospital |
Baba H.,Kumamoto University |
And 16 more authors.
The Lancet Oncology | Year: 2013
Background: Studies done in Asia have shown that a regimen of S-1 plus oxaliplatin (SOX) has promising efficacy and safety in patients with metastatic colorectal cancer. We aimed to establish whether SOX plus bevacizumab is non-inferior to mFOLFOX6 (modified regimen of leucovorin, fluorouracil, and oxaliplatin) plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer. Methods: We undertook an open-label, non-inferiority, randomised phase 3 trial in 82 sites in Japan. We enrolled individuals aged 20-80 years who had metastatic colorectal cancer, had an Eastern Cooperative Oncology Group performance status of 0 or 1, had assessable lesions, had received no previous chemotherapy or radiotherapy, could take drugs orally, and had adequate organ function. Eligible patients were randomly assigned (1:1) to receive either mFOLFOX6 plus bevacizumab (on day 1 of each 2-week cycle, 5 mg/kg intravenous infusion of bevacizumab and a simultaneous intravenous infusion of 85 mg/m2 oxaliplatin, 200 mg/m2 l-leucovorin, 400 mg/m2 bolus fluorouracil, and 2400 mg/m2 infusional fluorouracil) or SOX plus bevacizumab (on day 1 of each 3-week cycle, 7·5 mg/kg intravenous infusion of bevacizumab and 130 mg/m2 intravenous infusion of oxaliplatin; assigned dose of S-1 twice a day from after dinner on day 1 to after breakfast on day 15, followed by 7-day break). Randomisation was done centrally with the minimisation method, with stratification by institution and whether postoperative adjuvant chemotherapy had been given. Participants, investigators, and data analysts were not masked to treatment assignment. The primary endpoint was progression-free survival (PFS), which was defined as the interval between enrolment and progressive disease (≥20% increase in sum of longest dimensions of target lesions from baseline, or appearance of new lesions) or death, whichever came first. The primary analysis was done by modified intention to treat. This trial is registered with the Japan Pharmaceutical Information Center, number JapicCTI-090699. Findings: Between Feb 1, 2009, and March 31, 2011, 512 patients underwent randomisation. 256 patients assigned to receive SOX plus bevacizumab and 255 assigned to receive mFOLFOX6 plus bevacizumab were included in the primary analysis. Median PFS was 11·5 months (95% CI 10·7-13·2) in the group assigned to mFOLFOX6 plus bevacizumab and 11·7 months (10·7-12·9) in the group assigned to SOX plus bevacizumab (HR 1·04, 95% CI 0·86-1·27; less than non-inferiority margin of 1·33, pnon-inferiority=0·014). The most common haematological adverse events of grade 3 or higher were leucopenia (21 [8%] of 249 patients given mFOLFOX6 plus bevacizumab included in safety analysis vs six [2%] of 250 given SOX plus bevacizumab; p=0·0029) and neutropenia (84 [34%] vs 22 [9%]; p<0·0001). Grade 3 or higher anorexia (13 [5%] vs three [1%]; p=0·019) and diarrhoea (23 [9%] vs seven [3%]; p=0·0040) were significantly more common in patients given SOX plus bevacizumab than in those given mFOLFOX6 plus bevacizumab. We recorded seven treatment-related deaths (three in the group given mFOLFOX6 plus bevacizumab; four in that given SOX plus bevacizumab). Interpretation: SOX plus bevacizumab is non-inferior to mFOLFOX6 plus bevacizumab with respect to PFS as first-line treatment for metastatic colorectal cancer, and could become standard treatment in Asian populations. Funding: Taiho. © 2013 Elsevier Ltd.
PubMed | Mutsu General Hospital, Aomori General Health Examination Center, Misawa City Hospital and Hirosaki University
Type: Journal Article | Journal: Human cell | Year: 2016
We incorporated liquid-based cytology (LBC) in population-based screening for cervical cancer. The usefulness of using LBC in mass screening for cervical cancer was examined. From 2009 to 2014, 157,061 individuals underwent mass screening for cervical cancer in Aomori Prefecture. From 2009 to 2011, cells were collected from 82,218 individuals and the specimens were conventionally prepared (CP). From 2012 to 2014, cells were collected from 74,843 individuals and the specimens were prepared using LBC (TACAS). Cytology results for the 2 sets of specimens were compared and differences in cytologic features were examined. ASC-US and more severe lesions were detected at a rate of 1.13 % by CP and 1.44 % by LBC, so LBC had a 1.3-fold higher rate of detection. LBC had a 1.6-fold higher rate of LSIL detection and a 1.2-fold higher rate of HSIL detection. CP detected cancer in 20 cases at a rate of 0.024 % while LBC detected cancer in 18 cases at a rate of 0.024 %. Cytodiagnosis of the 18 cases of SCC that LBC identified revealed that 7 were SCC, 8 were HSIL, and 3 were ASC-H. Atypical cells tended to be smaller with TACAS. LBC reduced the time needed for microscopic examination of a single specimen by 42 % in comparison to CP. LBC using TACAS allowed the detection of slight lesions and slight changes in cells. LBC can lessen the burden on medical personnel and may lead to improved accuracy.
Monden M.,Osaka University |
Sakon M.,Nishinomiya Municipal Central Hospital |
Sakata Y.,Misawa City Hospital |
Ueda Y.,Otsuka Pharmaceutical Factory Inc. |
Hashimura E.,Otsuka Pharmaceutical Factory Inc.
Hepatology Research | Year: 2012
Aim: The efficacy and safety of 5-fluorouracil arterial infusion+interferon therapy (FAIT) was evaluated in patients with hepatocellular carcinoma (HCC) with a high degree of vascular invasion associated with poor prognosis, using best salvage therapy (BST) as a reference group. Methods: Sixty-nine patients with advanced HCC with a high degree of vascular invasion (Vp3, Vp4, Vv3) were randomly assigned to a FAIT group or a BST group. The FAIT group received interferon-α and 5-fluorouracil combination therapy; the BST group received either combination therapy of cisplatin and 5-fluorouracil (low-dose FP therapy) or cisplatin for arterial infusion. Results: Thirty patients in the FAIT group and 31 patients in the BST group were included in the efficacy analysis. The response rate (primary endpoint) was 26.7% (eight out of 30 patients) for the FAIT group and 25.8% (eight out of 31) for the BST group. The number of occurrences of adverse events of grade 3 or higher was 115 in 30 patients in the FAIT group and 113 in 29 patients in the BST group. None of the deaths were related to the study therapy. Conclusions: FAIT exerts modest antitumor effects and poses no particular safety concerns. FAIT may be a strategy of choice worth trying for advanced HCC with high degree of vascular invasion, which is associated with poor prognosis. © 2011 The Japan Society of Hepatology.
PubMed | Daiichi Sankyo, Kanagawa Cancer Center, National Defense Medical College, Chuo University and 11 more.
Type: Journal Article | Journal: Asia-Pacific journal of clinical oncology | Year: 2016
Irinotecan-induced severe toxicities are possibly related to UGT1A1*6 and *28 genotypes. However, the correlation between UGT1A1 polymorphisms and the risk of toxicities induced by low-dose irinotecan plus platinum combination therapy still remains controversial. This prospective observational study aimed to examine the correlation between UGT1A1 genotypes and clinical outcomes of low-dose irinotecan (median 60 mg/m(2) , range 25-115 mg/m(2) ) plus platinum in Japanese patients with solid tumors.Toxicity profiles were compared between UGT1A1 SNP heterozygotes (hetero-group) and patients with homozygous SNP profile (*6/*6, *28/*28 and *6/*28). Logistic regression models were used to identify independent risk factors for these toxicities.A total of 331 patients were enrolled: 84% with hetero-group and 16% with homo-group. Although the initial irinotecan dose was similar, the dose intensities during the three cycles were significantly lower in the homo-group (P < 0.01). Grade 3/4 hematological toxicities were significantly more frequent in the homo-group. Multivariable analysis identified UGT1A1 genotype (P < 0.01) as an independent factor for grade 4 hematological toxicity in the first treatment cycle.UGT1A1 genotype has a major impact on the increased risk of severe hematological toxicities, even in low-dose irinotecan regimens. UGT1A1 genotypes are useful biomarkers for predicting severe hematological toxicities in patients treated with irinotecan plus platinum analog.
PubMed | Shizuoka Cancer Center, Ageo Central General Hospital, Tochigi Cancer Center, Niigata Cancer Center Hospital and 9 more.
Type: Clinical Trial, Phase II | Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association | Year: 2016
Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy.The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum.Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age.The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.
PubMed | Misawa City Hospital and Hirosaki University
Type: Comparative Study | Journal: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons | Year: 2015
The purpose of the present study was to compare the incidence of osteoradionecrosis between superselective intra-arterial chemoradiotherapy and intravenous chemoradiotherapy and to verify the risk factors for osteoradionecrosis.Of the 79 patients with oral cancer, 40 were treated with intra-venous chemoradiotherapy and 39 were treated with superselective intra-arterial chemoradiotherapy. The incidence of, and risk factors for, osteoradionecrosis were evaluated using statistical analysis.Of the 79 patients, 4 (10%) of 40 in the intravenous chemoradiotherapy and 7 (17.9%) of 39 in the superselective intra-arterial chemoradiotherapy group developed osteoradionecrosis of the jaw. No significant difference was found between the 2 groups. Although the chemoradiotherapy methods, anatomic tumor location, smoking behavior, alcohol consumption, condition of teeth, teeth extraction before radiation, and progression of dental caries were considered predisposing factors for the occurrence of osteoradionecrosis, only progressive dental caries resulted in a significant difference for osteoradionecrosis.The present study is the first report comparing the incidence of osteoradionecrosis between superselective intra-arterial chemoradiotherapy and intravenous chemoradiotherapy. The administration methods of anticancer drugs were not related to the incidence of osteoradionecrosis in our study. From our study, dental caries is the most important risk factor for osteoradionecrosis; therefore, a radiation caries prevention program is crucial to control osteoradionecrosis.
PubMed | Misawa City Hospital and Hirosaki University
Type: Journal Article | Journal: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons | Year: 2016
The purpose of this study was to compare quality of life (QoL) and the survival rate after surgery with and without radiotherapy versus superselective intra-arterial chemoradiotherapy (SSIACRT) for advanced cancer of the tongue and floor of the mouth.Patients with stage III and IV squamous cell carcinoma of the tongue and floor of the mouth treated between 2000 and 2013 were included in this study. The predictor variables were surgery without radiotherapy, surgery followed by radiotherapy, and SSIACRT. The outcome variables were QoL and the survival rate. The University of Washington QoL questionnaire (UW-QOL) was used for evaluation of QoL. The Kaplan-Meier method was used to estimate the overall survival rate. The UW-QOL was analyzed by analysis of covariance, and the survival rate was analyzed statistically by the log-rank test.Sixty-two patients were eligible for this study. Of these, 13 were treated by surgery without radiotherapy, 29 were treated by surgery plus radiotherapy, and 20 were treated by SSIACRT. The SSIACRT group had the best UW-QOL scores among the 3 groups. The 5-year Kaplan-Meier disease-specific survival rates for these groups were 92.9%, 62.9%, and 83.2%, respectively, with no significant difference (P= .20) shown.The QoL scores of the SSIACRT group were the best among the 3 groups in most domains. The superiority of QoL and the survival rate in the SSIACRT group showed that SSIACRT should be preferred in managing advanced cancer of the tongue and floor of the mouth.
Koizumi W.,Kitasato University |
Morita S.,Kyoto University |
Sakata Y.,Misawa City Hospital
Japanese Journal of Clinical Oncology | Year: 2015
Paclitaxel is an agent widely used in second-line chemotherapy for advanced gastric cancer. The aim of this trial is to evaluate the efficacy and safety of 3-weekly or weekly doses of nanoparticle albuminbound- paclitaxel compared with weekly doses of Cremophor-based paclitaxel in patients with unresectable or recurrent gastric cancer refractory to first-line chemotherapy comprising fluoropyrimidines. A total of 730 patients will be enrolled from 72 institutions. The primary endpoint is the overall survival, and the secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, quality of life (by using the EQ-5D system) and safety. © The Author 2014.
PubMed | Misawa City Hospital
Type: Journal Article | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2017
A 52-year-old man visited a local hospital complaining of abdominal distension. Enhanced computed tomography scan revealed a giant retroperitoneal tumor surrounding the left internal iliac artery and left kidney. We performed en bloc tumor resection with left internal iliac artery resection. The tumor was 35 cm in size and weighed 6,860 g. The histological diagnosis was a dedifferentiated liposarcoma. After surgery, the patient experienced left lower limb paralysis. Clinical examination and neurological findings suggested a lumbosacral problem. After 6 months, the patients lower limb paralysis had not improved. It is important to note that ischemic neuropathy may be related to internal iliac artery resection.
PubMed | Kitasato University, Misawa City Hospital and Kyoto University
Type: Clinical Trial, Phase III | Journal: Japanese journal of clinical oncology | Year: 2015
Paclitaxel is an agent widely used in second-line chemotherapy for advanced gastric cancer. The aim of this trial is to evaluate the efficacy and safety of 3-weekly or weekly doses of nanoparticle albumin-bound-paclitaxel compared with weekly doses of Cremophor-based paclitaxel in patients with unresectable or recurrent gastric cancer refractory to first-line chemotherapy comprising fluoropyrimidines. A total of 730 patients will be enrolled from 72 institutions. The primary endpoint is the overall survival, and the secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, quality of life (by using the EQ-5D system) and safety.