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ABSTRACT: BACKGROUND: Regimens of standard-dose cisplatin have usually been administered as inpatient chemotherapy in Japan. This prospective study evaluated the feasibility of outpatient chemotherapy with standard-dose cisplatin in Japanese patients with advanced gastric cancer. METHODS: Advanced gastric cancer patients received an S-1 + cisplatin regimen (S-1: 80-120 mg days 1-21; cisplatin: 60 mg/m(2) day 8, every 4-5 weeks), either as outpatient chemotherapy with oral hydration on days 9-10, or as inpatient chemotherapy with intravenous hydration on days 9-10, based on the results of an oral hydration test during days 1-7 of the first cycle. The primary endpoint was the completion rate of two cycles in the outpatient group. RESULTS: A total of 36 patients were enrolled: 32 were allocated to the outpatient group and 4 to the inpatient group. The completion rate of two cycles in the outpatient group was 78% [90% confidence interval (CI): 63-89]. The median of the total number of treatment cycles of S-1 + cisplatin and the median progression-free survival in the outpatient group were 5 (range 1-11) and 10.6 months (95% CI 4.2-16.9), respectively. Although seven patients in the outpatient group discontinued treatment, mainly owing to gastrointestinal toxicity, most of them could continue S-1 + cisplatin by switching to inpatient chemotherapy from the next cycle. CONCLUSION: Outpatient chemotherapy with S-1 + cisplatin in advanced gastric cancer patients can be safely and effectively administered in Japan with appropriate patient selection and supportive treatment.
Gastric Cancer 02/2012; · 2.42 Impact Factor
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Junichi Matsubara,
Yasuhiro Shimada,
Ken Kato,
Yushi Nagai,
Satoru Iwasa, Takako E Nakajima,
Tetsuya Hamaguchi,
Yasuhide Yamada,
Seiichi Takagi,
Kazuma Kobayashi,
Akira Yoshioka,
Norisuke Nakayama,
Akihito Tsuji
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ABSTRACT: We evaluated the efficacy and safety of bolus 5-fluorouracil (5-FU) and leucovorin combined with weekly paclitaxel (FLTAX) in advanced gastric cancer (GC) patients.
Patients with untreated stage IV GC received paclitaxel 80 mg/m(2) as a 1-hour infusion, followed by 5-FU 600 mg/m(2) as a bolus infusion and L-leucovorin 250 mg/m(2) as a 2-hour infusion on days 1, 8 and 15. Treatment cycles were repeated every 28 days. The primary endpoint was response rate.
Thirty-five patients were enrolled. The median age was 62 years (range 34-75). Twenty-one patients (60%) had diffuse-type cancer and 11 had peritoneal metastasis. The confirmed response rate was 43% (95% CI 26-61) with 15 partial responses. Stable disease was observed in 16 (46%) patients. Median progression-free survival and overall survival were 6.8 months (95% CI 5.8-7.4) and 16.2 months (95% CI 10.0-22.8), respectively. Grade 3-4 adverse events were: neutropenia (54%), febrile neutropenia (3%), diarrhea (6%) and sensory neuropathy (11%).
FLTAX showed a desirable safety profile, and the efficacy against advanced GC was encouraging. FLTAX may be a good option for GC patients with deteriorated general condition, and a randomized clinical trial in such patients is currently underway.
Oncology 11/2011; 81(5-6):291-7. · 2.27 Impact Factor
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Natsuko Tsuda Okita,
Ken Kato,
Daisuke Takahari,
Yoshinori Hirashima, Takako E Nakajima,
Junichi Matsubara,
Tetsuya Hamaguchi,
Yasuhide Yamada,
Yasuhiro Shimada,
Hirokazu Taniguchi,
Kuniaki Shirao
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ABSTRACT: Neuroendocrine tumors (NETs) occur in various primary sites, but rarely in the stomach. NETs are classified into three types, carcinoids, malignant carcinoids and poorly differentiated neuroendocrine carcinomas (PNECs), whose clinical behavior is different. Currently, clinical outcomes and standard chemotherapy for NETs of the stomach remain unclear.
We conducted a retrospective review of histopathologically confirmed NETs of the stomach at our hospital between January 2000 and August 2006.
Thirty-seven NETs were identified. Fifteen patients had carcinoids while 22 had PNECs. Among the carcinoid patients, 7 underwent endoscopic mucosal resection and 5 had gastrectomy as first-line treatment. Three patients were observed without intervention. All patients were alive after an average follow-up period of 27 months. Among the 22 PNEC patients, 3 had no metastasis, 11 had regional lymph node metastasis, and 8 had distant metastasis. Eight of 14 patients relapsed at a median of 177 days (range 120-1459 days) after curative surgery. Twelve patients with metastatic or recurrent disease received palliative cisplatin plus irinotecan chemotherapy. The response rate was 75%, the median progression-free survival time was 212 days, and median survival time was 679 days.
Gastric PNEC patients with distant metastasis had poor outcomes. Regimens containing cisplatin plus irinotecan produced a good response in gastric PNEC.
Gastric Cancer 02/2011; 14(2):161-5. · 2.42 Impact Factor
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Junichi Matsubara,
Yasuhiro Shimada,
Ken Kato,
Yushi Nagai,
Satoru Iwasa, Takako E. Nakajima,
Tetsuya Hamaguchi,
Yasuhide Yamada,
Seiichi Takagi,
Kazuma Kobayashi,
Akira Yoshioka,
Norisuke Nakayama
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ABSTRACT: Objective: We evaluated the efficacy and safety of bolus 5-fluorouracil (5-FU) and leucovorin combined with weekly paclitaxel (FLTAX) in advanced gastric cancer (GC) patients. Methods: Patients with untreated stage IV GC received paclitaxel 80 mg/m2 as a 1-hour infusion, followed by 5-FU 600 mg/m2 as a bolus infusion and L-leucovorin 250 mg/m2 as a 2-hour infusion on days 1, 8 and 15. Treatment cycles were repeated every 28 days. The primary endpoint was response rate. Results: Thirty-five patients were enrolled. The median age was 62 years (range 34–75). Twenty-one patients (60%) had diffuse-type cancer and 11 had peritoneal metastasis. The confirmed response rate was 43% (95% CI 26–61) with 15 partial responses. Stable disease was observed in 16 (46%) patients. Median progression-free survival and overall survival were 6.8 months (95% CI 5.8–7.4) and 16.2 months (95% CI 10.0–22.8), respectively. Grade 3–4 adverse events were: neutropenia (54%), febrile neutropenia (3%), diarrhea (6%) and sensory neuropathy (11%). Conclusion: FLTAX showed a desirable safety profile, and the efficacy against advanced GC was encouraging. FLTAX may be a good option for GC patients with deteriorated general condition, and a randomized clinical trial in such patients is currently underway.Copyright © 2011 S. Karger AG, Basel
Oncology - ONCOLOGY-BASEL. 01/2011; 81:291-297.
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Yasuhide Yamada,
Tokuzo Arao,
Kazuko Matsumoto,
Vinita Gupta,
Woei Tan,
Joe Fedynyshyn, Takako E Nakajima,
Yasuhiro Shimada,
Tetsuya Hamaguchi,
Ken Kato,
Hirokazu Taniguchi,
Yutaka Saito,
Takahisa Matsuda,
Yoshihiro Moriya,
Takayuki Akasu,
Shin Fujita,
Seiichiro Yamamoto,
Kazuto Nishio
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ABSTRACT: This prospective study used antibody suspension bead arrays to identify biomarkers capable of predicting post-operative recurrence with distal metastasis in patients with colorectal cancer. One hundred colorectal cancer patients who underwent surgery were enrolled in this study. The median follow-up period was 3.9 years. The pre-operative plasma concentrations of 24 angiogenesis-related molecules were analyzed with regard to the TNM stage and the development of post-operative recurrence. The concentrations of half of the examined molecules (13/24) increased significantly according to the TNM stage (P < 0.05). Meanwhile, a multivariate logistic regression analysis revealed that the concentrations of vascular cell adhesion molecule 1 (VCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in the post-operative recurrence group. The VCAM-1 and PAI-1 model discriminated post-operative recurrence with an area under the curve of 0.82, a sensitivity of 0.75, and a specificity of 0.73. A leave-one-out cross-validation was applied to the model to assess the prediction performance, and the result indicated that the cross-validated error rate was 12.5% (12/96). In conclusion, our results demonstrate that antibody suspension bead arrays are a powerful tool to screen biomarkers in the clinical setting, and the plasma levels of VCAM-1 and PAI-1 together may be a promising biomarker for predicting post-operative recurrence in patients with colorectal cancer.
Cancer Science 08/2010; 101(8):1886-90. · 3.33 Impact Factor
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ABSTRACT: In Japan, standard first-line chemotherapy for metastatic gastric cancer was initially 5-fluorouracil (5-FU) monotherapy. This is based on the Japan Clinical Oncology Group (JCOG) 9205 phase III trial. Based on recent Japanese phase III trials, S1 plus cisplatin combination chemotherapy was established as the standard first-line chemotherapy, and this combination has met the global standard regimen of 5-FU (capecitabine) plus a platinum analog (cisplatin or oxaliplatin). Since the same standard regimen has been established outside Japan, many global trials are currently ongoing in other countries aside from Japan. With the recent development of many molecular targeted agents, global collaboration in clinical trials is necessary for their immediate evaluation. We review the results of recent phase III trials of first-line chemotherapy for metastatic gastric cancer in Japan and other countries.
Gastrointestinal cancer research: GCR 11/2009; 3(6):239-44.
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Junichi Matsubara,
Yasuhiro Shimada,
Atsuo Takashima,
Daisuke Takahari,
Yoshinori Hirashima,
Natsuko T Okita, Takako E Nakajima,
Ken Kato,
Tetsuya Hamaguchi,
Yasuhide Yamada,
Kuniaki Shirao
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ABSTRACT: To determine the dose-limiting toxicity (DLT) and the maximum-tolerated dose (MTD) of combination chemotherapy with leucovorin-modulated weekly bolus 5-fluorouracil (5-FU) and weekly paclitaxel in patients with advanced gastric cancer (GC).
Chemotherapy-naive patients with histologically proven metastatic or recurrent GC were enrolled. Paclitaxel was administered as a 1-h intravenous (i.v.) infusion followed by 5-FU as a bolus i.v. infusion on Days 1, 8 and 15. A 2-h i.v. infusion of l-leucovorin was started at the same time as the paclitaxel infusion on Days 1, 8 and 15. Treatment cycles were repeated every 28 days until disease progression or unacceptable toxicity occurred. Patients were scheduled to receive 5-FU, l-leucovorin and paclitaxel at four dose levels (mg/m(2)/week): 500/250/60 (level 1), 500/250/80 (level 2), 600/250/80 (level 3) and 600/250/100 (level 4), respectively.
Eighteen patients were enrolled. During the first cycle of the highest dose level (level 4), two of the six patients had DLT involving Grade 3 diarrhea and Grade 3 skin rash. Furthermore, three of the four patients who received the second consecutive cycle of treatment at dose level 4 had Grade 4 neutropenia. Dose level 3 was thus determined to be the MTD. Eleven (61%) of the 18 patients had partial responses, and the median progression-free survival time was 6.8 months.
The MTD and the recommended dose for phase II studies of this regimen were determined to be 5-FU 600 mg/m(2)/week, l-leucovorin 250 mg/m(2)/week and paclitaxel 80 mg/m(2)/week.
Japanese Journal of Clinical Oncology 08/2008; 38(8):540-6. · 1.78 Impact Factor
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ABSTRACT: To better understand the clinical implications of insulin-like growth factor type 1 receptor (IGF-1R), epidermal growth factor receptor (EGFR) and HER2 expressions in gastric cancer (GC).
The study group comprised 86 patients who received first-line chemotherapy for advanced GC at the National Cancer Center Hospital. Using laser-captured microdissection and a real-time RT-PCR assay, we quantitatively evaluated mRNA levels of IGF-1R, EGFR and HER2 in paraffin-embedded cancer specimens of surgically removed primary tumors.
In univariate analysis of the study group as a whole, patients with low expression of both IGF-1R and EGFR (n = 13) had a significantly longer overall survival than the other patients (n = 51; median, 24.6 vs. 12.8 months; log-rank p = 0.013). Multivariate survival analysis demonstrated that high EGFR expression [hazard ratio, HR: 2.94 (95% confidence interval, CI: 1.40-6.17), p = 0.004] and poor performance status [HR: 1.96 (95% CI: 1.12-3.42), p = 0.018] were significant predictors of poor survival. In patients given first-line S-1 monotherapy (n = 29), low IGF-1R (p = 0.002) and low EGFR (p = 0.035) gene expression correlated with a better response, without a significant prolongation of survival.
Our data warrant further investigations on the strategy of co-targeting IGF-1R and EGFR in GC.
Oncology 02/2008; 74(1-2):76-83. · 2.27 Impact Factor
