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1.
S. Okada T. Sato T. Okusaka H. Ishii M. Ikeda H. Nakasuka H. Kosakamoto M. Yoshimori K. Wakabayashi 《British journal of cancer》1998,77(11):2028-2031
The aim of the study was to determine whether past exposure to hepatitis B virus (HBV) influences the risk of the development of hepatocellular carcinoma (HCC) in Japanese patients with chronic liver disease (CLD). We conducted a hospital-based case-control study of 141 HCC patients with CLD and 151 controls with CLD but without HCC. Past exposure to HBV was assessed by antibody to hepatitis B core antigen (anti-HBc) positivity. Ninety-two patients (65%) with HCC were anti-HBc positive compared with 65 patients (43%) with CLD alone (P < 0.01). A multivariate analysis using logistic regression modelling revealed that anti-HBc positivity significantly increased the risk of the development of HCC [odds ratio (OR) 2.0, P = 0.01]. In the anti-HBc-positive patients, a significantly increased risk of HCC was seen among the patients positive for anti-HBc alone (OR, 2.6; P < 0.01). However, a significant OR was not obtained among the patients with a transient HBV infection implied by positivity for both antibody to hepatitis B surface antigen and anti-HBc (OR, 1.5; P = 0.48). These results indicate that past exposure to HBV is a risk factor for HCC in Japanese CLD patients, especially when they have no serological evidence of immunity to HBV. 相似文献
2.
Surgical resection offers the only curative strategy for pancreatic cancer. Yet, because early detection of pancreatic cancer is so difficult and diagnosis is delayed, pancreatic cancer in most patients is surgically unresectable. Even in patients with resectable disease, the long-term outcome remains unsatisfactory due to early recurrence after resection. Early appearance of distant metastasis suggests that systemic treatment, such as chemotherapy, should play a major role in improving patient survival. Although the recently developed gemcitabine has renewed interest in clinical research for pancreatic cancer, other currently available chemotherapeutic agents have little impact on survival. Studies to identify more effective agents or treatment regimens must have the highest priority. The expanding understanding of molecular and genetic biology should facilitate research to develop novel molecule-targeted agents and to establish individualized therapy regimens for this disease. 相似文献
3.
Okusaka Takuji Ikeda Kenji Kudo Masatoshi Finn Richard Qin Shukui Han Kwang-Hyub Cheng Ann-Lii Piscaglia Fabio Kobayashi Masahiro Sung Max Chen Minshan Wyrwicz Lucjan Yoon Jung-Hwan Ren Zhenggang Mody Kalgi Dutcus Corina Tamai Toshiyuki Ren Min Hayato Seiichi Kumada Hiromitsu 《Journal of gastroenterology》2021,56(6):570-580
Journal of Gastroenterology - REFLECT was an open-label, phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib in patients with unresectable hepatocellular carcinoma... 相似文献
4.
Fujishiro M Okada S Ueno H Okusaka T Ikeda M Watanabe H Tanaka N 《Hepato-gastroenterology》2000,47(36):1744-1746
BACKGROUND/AIMS: Systemic chemotherapy for pancreatic adenocarcinoma, at present, has been of limited value in clinical practice and only a small portion of patients obtains meaningful palliation. METHODOLOGY: We retrospectively examined 96 patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy to determine factors predictive of tumor response. None of the patients had received any prior anti-cancer treatment except for pancreatectomy. RESULTS: Of these 96 patients, 5 patients (5.2%) showed partial response but none showed complete response. There was no responder with a performance status of 2 or 3, serum albumin level less than 3.5 g/dL, serum total bilirubin level equal to or more than 2.0 mg/dL, or peritoneal dissemination. Response rates tended to be higher in the subgroups of female patients, those with serum albumin level > or = 3.5 g/dL and those with serum carcinoembryonic antigen level < 10 ng/mL, although there were no significant differences. CONCLUSIONS: Patients with a poor performance status, hypoalbuminemia, jaundice, or peritoneal dissemination might be inappropriate candidates for systemic chemotherapy and might be treated with other experimental approaches or supportive care. 相似文献
5.
Junki Mizusawa Akira Fukutomi Hiroshi Katayama Hiroshi Ishii Tatsuya Ioka Takuji Okusaka Hideki Ueno Makoto Ueno Masafumi Ikeda Nobumasa Mizuno Masato Ozaka Haruhiko Fukuda Junji Furuse 《Pancreatology》2018,18(7):841-845
Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143. 相似文献
6.
Ikeda M Okada S Ueno H Okusaka T Tanaka N Kuriyama H Yoshimori M 《Hepato-gastroenterology》2000,47(33):862-865
BACKGROUND/AIMS: Sequential administration with methotrexate and 5-fluorouracil (sequential MTX/5-FU) has synergistic cytotoxic activity for several malignant diseases, but its activity in pancreatic cancer has not been fully evaluated. The aim of this study was to evaluate the antitumor activity and toxicity of sequential MTX/5-FU in metastatic pancreatic cancer. METHODOLOGY: All patients were required to have a pathologic diagnosis of pancreatic adenocarcinoma with measurable metastatic lesions, and no prior chemotherapy. Sequential MTX/5-FU was administered weekly as followed; MTX 100 mg/m2 intravenous bolus infusion was given, followed 3 h later by 5-fluorouracil 600 mg/m2 intravenous infusion over 30 min. RESULTS: Thirty-one patients were enrolled and assessable for response and toxicity. There were no complete responses, 4 partial responses, 10 no change and 17 progressive disease. The response rate was 12.9% (95% confidence interval: 1.1-24.7%) and the duration of response was 7.1 months (range: 5.5-9.1 months). The median survival was 4.0 months. Chemotherapy was well tolerated, although grade 3-4 toxicities such as neutropenia and diarrhea were seen infrequently. CONCLUSIONS: The sequential MTX/5-FU had marginal antitumor activity with mild toxicity against metastatic pancreatic cancer. 相似文献
7.
Tomoko Katsui Taniyama Chigusa Morizane Kohei Nakachi Satoshi Nara Hideki Ueno Shunsuke Kondo Tomoo Kosuge Kazuaki Shimada Minoru Esaki Masafumi Ikeda Shuichi Mitsunaga Taira Kinoshita Masaru Konishi Shinichiro Takahashi Takuji Okusaka 《Pancreatology》2012,12(5):428-433
ObjectivesA global consensus on how to treat recurrent pancreatic cancer after adjuvant chemotherapy with gemcitabine (ADJ-GEM) does not exist.MethodsWe retrospectively reviewed the clinical data of 41 patients with recurrences who were subsequently treated with chemotherapy.ResultsThe patients were divided into two groups according to the time until recurrence after the completion of ADJ-GEM (ADJ-Rec): patients with an ADJ-Rec < 6 months (n = 25) and those with an ADJ-Rec ≥ 6 months (n = 16). The disease control rate, the progression-free survival after treatment for recurrence and the overall survival after recurrence for these two groups were 68 and 94% (P = 0.066), 5.5 and 8.2 months (P = 0.186), and 13.7 and 19.8 months (P = 0.009), respectively. Furthermore, we divided the patients with an ADJ-Rec < 6 months into two groups: patients treated with gemcitabine (n = 6) and those treated with alternative regimens including fluoropyrimidine-containing regimens (n = 19) for recurrent disease. Patients treated with the alternative regimens had a better outcome than those treated with gemcitabine.ConclusionsFluoropyrimidine-containing regimens may be a reasonable strategy for recurrent disease after ADJ-GEM and an ADJ-Rec < 6 months. 相似文献
8.
Yu Sunakawa Junji Furuse Takuji Okusaka Masafumi Ikeda Fumio Nagashima Hideki Ueno Shuichi Mitsunaga Kensei Hashizume Yuichiro Ito Yasutsuna Sasaki 《Investigational new drugs》2014,32(1):104-112
The safety, pharmacokinetics, and antitumor activity of the multikinase inhibitor regorafenib in Japanese patients was assessed in this multicenter, single-arm, phase I trial. Fifteen patients with treatment-refractory advanced solid tumors received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle until disease progression, unacceptable toxicity, or investigator or patient decision to stop. The median duration of treatment was 2.1 months (range, 0.9–20.1 months). At data cutoff, one patient was still receiving regorafenib in cycle 21. Reasons for treatment discontinuation were disease progression (n?=?12) and adverse events (liver enzyme elevation n?=?1; anemia n?=?1). Adverse events necessitated dose reduction in six patients, interruption of daily treatment in seven patients, and cycle delay in four patients. All patients experienced at least one drug-related adverse event, particularly gastrointestinal (87 %), dermatologic (73 %), or hematologic (67 %) events. There was no significant change in time to maximum concentration or terminal half-life of regorafenib and its active metabolites M2 and M5 between single dosing and 21-day continuous dosing. The area under the concentration–time curve was 2.1-fold higher for regorafenib, 5.2-fold higher for M2, and 37.3-fold higher for M5, and the maximum concentration was 2.0-fold, 4.8-fold, and 36.0-fold higher, respectively, after continuous dosing than after single dosing. One patient had a partial response (duration 10.5 months) and seven patients had stable disease. This study indicates that regorafenib 160 mg orally once daily (21 days on/7 days off treatment) can be given to Japanese patients who have solid tumors, without undue toxicity. 相似文献
9.
Okusaka Takuji; Okada Shuichi; Ishii Hiroshi; Nose Haruhiko; Nakasuka Hidekazu; Nakayama Hidetsugu; Nagahama Hiroyasu 《Japanese journal of clinical oncology》1996,26(4):215-220
Pancreatic cancer shows high mortality and has a poor prognosis.Although the rate of response to all chemotherapeutic regimensis low, some patients have shown improvement of their symptomsafter chemotherapy and/or radiotherapy without obvious tumorregression. We assessed the clinical benefit of systemic combinedchemotherapy with 5-fluorouracil and cisplatin (FP therapy)in 21 patients with advanced cancer of the pancreas. The clinicalresponse to FP therapy was evaluated using two parameters: pain(intensity of pain and consumption of morphine) and performancestatus. A patient was considered to be a clinical responderif one of two parameters was positive and the other was positiveor stable. Four patients (19%) responded. Two of the respondersachieved partial response according to the objective tumor response,and the remaining two showed no change. The survival periodin responders was significant longer than in the other patients.The clinical response may be one parameter for evaluating theresults of treatment for pancreatic cancer, and the longer survivalperiod of the clinical responders in this study supports thisnotion. 相似文献
10.
Ueno H Okada S Okusaka T Ikeda M Kuriyama H 《Cancer chemotherapy and pharmacology》2002,49(2):155-160
PURPOSE: In this study the maximum tolerated dose of 5-fluorouracil administered by 5-day (120-h) continuous infusion every 4 weeks was investigated and the pharmacokinetics in patients with hepatocellular carcinoma were evaluated. METHODS: Patients with hepatocellular carcinoma no longer amenable to established forms of treatment were eligible for the study. The starting dose of 5-fluorouracil was 300 mg/m(2) per day and doses were escalated in 50 mg/m(2) per day increments in successive cohorts of three new patients if tolerated. Pharmacokinetic studies were performed at the time of the first course of therapy. RESULTS: Enrolled in the study were 20 patients. The maximum tolerated dose was 500 mg/m(2) per day and the dose-limiting toxicity was stomatitis. Other toxicities were mild and well tolerated. Age, gender and associated liver cirrhosis were significant factors influencing 5-fluorouracil clearance. With regard to biochemical parameters, serum alanine aminotransferase and cholesterol levels were correlated with 5-fluorouracil clearance. CONCLUSIONS: The maximum tolerated dose for 5-day continuous infusion of 5-fluorouracil in hepatocellular carcinoma patients was 500 mg/m(2) per day. The recommended dose for phase II studies using this schedule is 450 mg/m(2) per day. Furthermore, the pharmacokinetic data obtained in this study may be useful in determining chemotherapy dosage adjustments for reduction of toxicity. 相似文献