Publications (13)88.74 Total impact
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Article: A phase II study of biweekly mitomycin C and irinotecan combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer: a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group (JCOG0109-DI Trial).
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ABSTRACT: Preclinical studies have shown that mitomycin C (MMC) acts synergistically with irinotecan (CPT-11). In this phase II study, we evaluated the efficacy and toxicity of MMC/CPT-11 therapy as second-line chemotherapy for patients with fluoropyrimidine-resistant advanced gastric cancer. Eligible patients had evidence of tumor progression despite prior treatment with fluoropyrimidine-based regimens or had relapsed within 6 months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of MMC (5 mg/m(2)) and CPT-11 (150 mg/m(2)) administered i.v. every 2 weeks. The primary endpoint was the response rate (RR). Our hypothesis was that this combination therapy was efficacious when the lower boundary of the 95% confidence interval (CI) of the RR exceeded 20% of the threshold RR. Between April 2002 and July 2003, 45 eligible patients were registered and analyzed. Among the 45 patients, 40 (89%) had previously received chemotherapy for metastasis and 24 (53%) had a performance status (PS) of 0. Thirteen partial responses were obtained among the 45 patients, resulting in an overall RR of 29% (95% CI, 16-42%). The median time to progression was 4.1 months, and the median survival time was 10 months, with a 1-year survival rate of 36%. Grade 4 neutropenia was observed in 29% of the patients, whereas febrile neutropenia occurred in 9%. The incidence rates of grade 3 nausea and diarrhea were 13 and 2%, respectively. Although this study did not achieve the per-protocol definition of activity, the progression-free survival and overall survival appeared to be promising, with acceptable tolerability. Thus, MMC/CPT-11 therapy as second-line chemotherapy for fluoropyrimidine-resistant advanced gastric cancer presents a potential treatment option in patients with a good PS.Gastric Cancer 04/2011; 14(3):226-33. · 2.42 Impact Factor -
Article: Randomized phase II study of carboplatin-paclitaxel or gemcitabine-vinorelbine in patients with advanced nonsmall cell lung cancer and a performance status of 2: West Japan Thoracic Oncology Group 0004.
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ABSTRACT: The aim of the present study was to evaluate the efficacy and safety of carboplatin plus paclitaxel versus gemcitabine plus vinorelbine in patients with advanced nonsmall cell lung cancer (NSCLC) and an Eastern Cooperative Oncology Group performance status (PS) of 2. Chemotherapy-naive patients with NSCLC of stage IIIB or IV and a PS of 2 were eligible. The patients received 3-week cycles of carboplatin (area under the curve of 6) plus paclitaxel (200 mg/m(2)) on day 1 (CP) or gemcitabine (1000 mg/m(2)) plus vinorelbine (25 mg/m(2)) on days 1 and 8 (GV). The primary end point was 1-year survival rate for selection of the better treatment arm for further study. Of the 89 patients enrolled, 84 were assessable (41 in the CP arm, 43 in the GV arm). The overall response rate, median survival time, and 1-year survival rate were 29.3%, 5.9 months, and 22.0%, respectively, for the CP arm and 20.9%, 6.0 months, and 27.9% for the GV arm. Common toxicities of grade 3 or 4 included neutropenia (67.5% for the CP arm vs. 65.1% for the GV arm), febrile neutropenia (20% vs. 14%), and infection (25.0% vs. 23.2%). The frequency of nausea of grade 3 was greater for the CP arm (17.5% vs. 2.3%), whereas that of anemia of grade 3 or 4 (30.2% vs. 12.5%) or treatment-related death (7.0% vs. 2.4%) was greater for the GV arm. The 1-year survival rate did not exceed 30% for either doublet chemotherapy. Furthermore, each treatment was associated with a substantial degree of toxicity.American journal of clinical oncology 02/2011; 35(1):58-63. · 2.21 Impact Factor -
Article: Phase II study of sequential triplet chemotherapy, irinotecan and cisplatin followed by amrubicin, in patients with extensive-stage small cell lung cancer: West Japan Thoracic Oncology Group Study 0301.
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ABSTRACT: Combination chemotherapy of irinotecan, a topoisomerase I inhibitor, and cisplatin is a standard treatment in patients with extensive-stage small cell lung cancer (SCLC). Amrubicin, a novel 9-aminoanthracycline, inhibits topoisomerase II. We investigated a sequential triplet chemotherapy consisting of irinotecan and cisplatin followed by amrubicin in patients with extensive-stage SCLC. Eligible patients were aged 20 to 70 years and had Eastern Cooperative Oncology Group performance status of 0 or 1, measurable lesions, and adequate organ functions. Chemotherapy consisted of irinotecan 60 mg/m on days 1 and 8 plus cisplatin 60 mg/m on day 1 every 3 weeks for three cycles and then amrubicin 40 mg/m alone on days 1 to 3 every 3 weeks for three cycles. From September 2004 to September 2006, 45 patients were enrolled, 43 were evaluable for response and survival, and 44 were evaluable for toxicity. Twenty-eight patients (64%) completed the full planned chemotherapy. One patient achieved complete response and 33 had partial response for an overall response rate of 79%. Median progression-free survival was 6.5 months. Median overall survival was 15.4 months. Major toxicity was myelosuppression. Grade 3 or 4 neutropenia, anemia, thrombocytopenia, and febrile neutropenia occurred in 57%, 7%, 0%, and 7% of patients during irinotecan/cisplatin cycles and in 91%, 27%, 9%, and 15% of patients during amrubicin cycles, respectively. The sequential triplet chemotherapy, irinotecan and cisplatin followed by amrubicin, is an effective and well-tolerated treatment in patients with extensive-stage SCLC. Further investigation of this treatment is warranted.Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2010; 5(7):1075-80. · 4.55 Impact Factor -
Article: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial.
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ABSTRACT: Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor (EGFR) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib. However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain. We did an open label, phase 3 study (WJTOG3405) with recruitment between March 31, 2006, and June 22, 2009, at 36 centres in Japan. 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned, using a minimisation technique, to receive either gefitinib (250 mg/day orally; n=88) or cisplatin (80 mg/m(2), intravenously) plus docetaxel (60 mg/m(2), intravenously; n=89), administered every 21 days for three to six cycles. The primary endpoint was progression-free survival. Survival analysis was done with the modified intention-to-treat population. This study is registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539. Five patients were excluded (two patients were found to have thyroid and colon cancer after randomisation, one patient had an exon 18 mutation, one patient had insufficient consent, and one patient showed acute allergic reaction to docetaxel). Thus, 172 patients (86 in each group) were included in the survival analyses. The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup, with a median progression-free survival time of 9.2 months (95% CI 8.0-13.9) versus 6.3 months (5.8-7.8; HR 0.489, 95% CI 0.336-0.710, log-rank p<0.0001). Myelosuppression, alopecia, and fatigue were more frequent in the cisplatin plus docetaxel group, but skin toxicity, liver dysfunction, and diarrhoea were more frequent in the gefitinib group. Two patients in the gefitinib group developed interstitial lung disease (incidence 2.3%), one of whom died. Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel. West Japan Oncology Group (WJOG): a non-profit organisation supported by unrestricted donations from several pharmaceutical companies.The lancet oncology 12/2009; 11(2):121-8. · 14.47 Impact Factor -
Article: Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study.
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ABSTRACT: The best chemotherapy regimen for metastatic gastric cancer is uncertain, but promising findings have been reported with irinotecan plus cisplatin and S-1 (tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate). We aimed to investigate the superiority of irinotecan plus cisplatin and non-inferiority of S-1 compared with fluorouracil, with respect to overall survival, in patients with metastatic gastric cancer. We undertook a phase 3 open label randomised trial in 34 institutions in Japan. We enrolled patients aged 20-75 years or younger, who had histologically proven gastric adenocarcinoma, and randomly assigned them by minimisation to receive either: a continuous infusion of fluorouracil (800 mg/m(2) per day, on days 1-5) every 4 weeks (n=234); intravenous irinotecan (70 mg/m(2), on days 1 and 15) and cisplatin (80 mg/m(2), on day 1) every 4 weeks (n=236); or oral S-1 (40 mg/m(2), twice a day, on days 1-28) every 6 weeks (n=234). The primary endpoint was overall survival. Analyses were done by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00142350, and with UMIN-CTR, number C000000062. All randomised patients were included in the primary analysis. Median overall survival was 10.8 months (IQR 5.7-17.8) for individuals assigned fluorouracil, 12.3 months (8.1-19.5) for those allocated irinotecan plus cisplatin (hazard ratio 0.85 [95% CI 0.70-1.04]; p=0.0552), and 11.4 months (6.4-21.3) for those assigned S-1 (0.83 [0.68-1.01]; p=0.0005 for non-inferiority). Three treatment-related deaths occurred in the irinotecan plus cisplatin group and one was recorded in the S-1 group. S-1 is non-inferior to fluorouracil and, in view of the convenience of an oral administration, could replace intravenous fluorouracil for treatment of unresectable or recurrent gastric cancer, at least in Asia. Irinotecan plus cisplatin is not superior to fluorouracil in this setting.The lancet oncology 10/2009; 10(11):1063-9. · 14.47 Impact Factor -
Article: Phase II trial of amrubicin for second-line treatment of advanced non-small cell lung cancer: results of the West Japan Thoracic Oncology Group trial (WJTOG0401).
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ABSTRACT: Amrubicin is a synthetic anthracycline drug that is a potent inhibitor of topoisomerase II. We have performed a multicenter phase II trial to evaluate the efficacy and safety of amrubicin for patients with previously treated non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who experienced disease recurrence after one platinum-based chemotherapy regimen were eligible for enrollment in the study. Amrubicin was administered by intravenous injection at a dose of 40 mg/m2 on 3 consecutive days every 3 weeks. Sixty-one enrolled patients received a total of 192 treatment cycles (median, 2; range, 1-15). Response was as follows: complete response, 0; partial response, seven (11.5%); stable disease, 20 (32.8%); and progressive disease, 34 (55.7%). Median progression-free survival was 1.8 months, whereas median overall survival was 8.5 months, and the 1-year survival rate was 32%. Hematologic toxicities of grade 3 or 4 included neutropenia (82.0%), leukopenia (73.8%), thrombocytopenia (24.6%), and anemia (27.9%). Febrile neutropenia occurred in 18 patients (29.5%). One treatment-related death due to infection was observed. Nonhematologic toxicities were mild. Amrubicin is a possible alternative for second-line treatment of advanced NSCLC, although a relevant hematological toxicity is significant, especially with a febrile neutropenia.Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2009; 5(1):105-9. · 4.55 Impact Factor -
Article: Significance of biological markers for predicting prognosis and selecting chemotherapy regimens of advanced gastric cancer patients between continuous infusion of 5-FU and a combination of 5-FU and cisplatin.
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ABSTRACT: Our previous phase II study of 5-fluorouracil (5-FU) and cisplatin (FP) for treatment of advanced gastric cancer showed that strong immunoreactivity for vascular endothelial growth factor (VEGF) is associated with chemoresponse. Patients with four or five of the favorable phenotypes, p53 (-), bcl-2 (-), gluthathione S-transferase pi (-), thymidylate synthase (-), and VEGF (+), survived longer than those with three or less of these phenotypes. The purpose of this study is to confirm our previous results and to compare the significance of those markers between continuous infusion of 5-FU (5-FUci) and FP. Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolled to JCOG9205 were analyzed immunohistochemically for the presence of the five markers. Median survival times of patients treated with 5-FUci (n = 65) or FP (n = 66) were 216 and 253 days, respectively (P = 0.6953). After FP treatment, patients with four or five favorable phenotypes (n = 20) survived longer than those with three or less favorable phenotypes (n = 46) (334 days and 243 days, respectively; P = 0.0463), and the survival times of 34 and 32 patients with VEGF (-) and (+) were similar (269 days and 253 days, respectively; P = 0.6317). After 5-FUci, 30 patients with VEGF (+) survived for a shorter time than 35 patients with VEGF (-) (142 days and 302 days, respectively; P = 0.0043). The number of favorable phenotypes is prognostic for gastric cancer patients treated with FP, and VEGF has a different impact on survival between treatment with 5-FUci and FP.Japanese Journal of Clinical Oncology 05/2007; 37(4):275-81. · 1.78 Impact Factor -
Article: Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902.
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ABSTRACT: We initially conducted a randomized phase II study to compare irinotecan and cisplatin (IP) versus irinotecan, cisplatin, and etoposide (IPE) after etoposide and cisplatin (EP) with concurrent twice-daily thoracic radiotherapy (TRT) in limited-disease small-cell lung cancer (LD-SCLC). We amended the protocol to evaluate IP after EP with concurrent twice-daily TRT in a single-arm phase II study because of an unacceptable toxicity in IPE. Previously untreated patients with LD-SCLC were treated intravenously with etoposide 100 mg/m2 on days 1 through 3 and cisplatin 80 mg/m2 on day 1 with concurrent twice-daily TRT (1.5 Gy per fraction, a total dose of 45 Gy) beginning on day 2 followed by three cycles of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 of a 4-week cycle. Of the 51 patients enrolled, 49 patients were assessable for response and toxicity. The overall response rate and complete response rate were 88% and 41%, respectively. The median survival time for all patients was 23 months. The 2-year and 3-year survival rates were 49% and 29.7%, respectively. The median progression-free survival was 11.8 months. The major toxicities observed were neutropenia (grade 4, 84%), febrile neutropenia (grade 3, 31%), infection (grade 3 to 4, 33%), electrolytes imbalance (grade 3 to 4, 20%), and diarrhea (grade 3 to 4, 14%). EP with concurrent twice-daily TRT followed by the consolidation of IP appears to be an active regimen which deserves further phase III testing in patients with LD-SCLC.Journal of Clinical Oncology 12/2006; 24(33):5247-52. · 18.37 Impact Factor -
Article: Phase II study of 3-week scheduling of irinotecan in combination with cisplatin in patients with advanced nonsmall-cell lung cancer.
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ABSTRACT: The combination of irinotecan and cisplatin given every 4 weeks is one of the standard treatments for advanced nonsmall-cell lung cancer (NSCLC) in Japan. The purpose of this study is to evaluate the efficacy, safety and dose-intensity as a measure of the feasibility of 3-week scheduling of irinotecan and cisplatin in patients with advanced NSCLC in phase II study. Previously untreated patients with stage IIIB and IV NSCLC were treated intravenously with irinotecan (60 mg/m2) on days 1 and 8 and cisplatin (60 mg/m2) on day 1 of a 3-week cycle. Of the 28 patients enrolled, 27 were evaluable for response and toxicity. The response rate was 30% (95% confidence interval, 14-50%). The median duration of response was 16 weeks (range, 10-26 weeks). The median survival time for all patients was 52 weeks and the 1-year and 2-year survival rates were 48% and 29%, respectively. The dose-intensity of irinotecan was 34 mg/m2/wk (range, 19-40). The major toxicities observed were neutropenia (grade 3, 30%; 4, 30%), leukopenia (grade 3, 30%), and diarrhea (grade 3, 22%). Other toxicities were generally mild. Three-week scheduling of irinotecan and cisplatin is effective and feasible in advanced NSCLC.American journal of clinical oncology 11/2006; 29(5):503-7. · 2.21 Impact Factor -
Article: Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with irinotecan and cisplatin.
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ABSTRACT: Previously we reported that immunohistochemical examination of p53, bcl-2, glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and vascular endothelial growth factor (VEGF) in biopsy samples was a useful method for predicting clinical outcome of gastric cancer patients treated with 5-fluorouracil and cisplatin. Here, we investigated if these biological markers can predict chemoresponse and survival of unresectable gastric cancer patients treated with irinotecan and cisplatin. The subjects were 55 unresectable gastric cancer patients treated with irinotecan (70 mg/m(2), Days 1 and 15) and cisplatin (80 mg/m(2), Day 1). Expression of p53, bcl-2, VEGF was examined immunohistochemically in biopsy samples. The overall response rate and the median survival time were 55% (30/55) and 321 days, respectively. Thirty patients with intestinal-type adenocarcinoma survived longer than 25 patients with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive, which were in accordance with previous findings. The response rate was significantly correlated with the total number of these favorable phenotypes (P = 0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2-negative and VEGF-positive) survived longer than the remaining 16 patients (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of the favorable phenotypes showed a tendency to correlate with survival after adjustment for potentially prognostic factors such as histological type or performance status (P = 0.070). Immunohistochemical examination of biological markers may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with irinotecan and cisplatin.Japanese Journal of Clinical Oncology 01/2006; 35(12):714-9. · 1.78 Impact Factor -
Article: Phase II study of sequential methotrexate and 5-fluorouracil chemotherapy against peritoneally disseminated gastric cancer with malignant ascites: a report from the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group, JCOG 9603 Trial.
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ABSTRACT: The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting. The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration. Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%). Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.Japanese Journal of Clinical Oncology 07/2004; 34(6):316-22. · 1.78 Impact Factor -
Article: Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205).
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ABSTRACT: To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial. A total of 280 patients with advanced gastric cancer were randomly allocated and analyzed for survival, response, and toxicity. The survival curves were compared between groups by log-rank test on an intent-to-treat basis. At the interim analysis, the UFTM arm showed a significantly inferior survival with higher incidences of hematologic toxic effects than did control arm FU alone, and the registration to UFTM was terminated. Both investigational regimens, FP and UFTM, had a significantly higher incidence of hematologic toxic effects than FU alone, although the effects were manageable. The overall response rates of the FU-alone, FP, and UFTM arms were 11%, 34%, and 9%, respectively. The median progression-free survival was 1.9 months with FU alone, 3.9 months with FP, and 2.4 months with UFTM, respectively. Although FP demonstrated a higher response rate (P <.001) and longer progression-free survival than did FU alone (P <.001), no differences in overall survival were observed between the arms. The median survival times and 1-year survival rates were 7.1 months and 28% with FU, 7.3 months and 29% with FP, and 6.0 months and 16% with UFTM, respectively. Neither investigational regimen, FP nor UFTM, showed a survival advantage as compared with FU alone. FU alone will remain a reference arm in our future trial for advanced gastric cancer.Journal of Clinical Oncology 01/2003; 21(1):54-9. · 18.37 Impact Factor -
Article: A phase II study of doxifluridine in elderly patients with advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG 9410).
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ABSTRACT: A previous phase II study of doxifluridine in non-elderly patients with advanced gastric cancer demonstrated a favorable survival with mild toxicity, despite a low response rate. The objectives of this study were to evaluate efficacy and feasibility of this agent for elderly patients. This study protocol required elderly patients, aged 76-80 years, with advanced gastric cancer and having no prior chemotherapy. Doxifluridine, at a dose of 1400 mg/m(2)/day, was administered for four consecutive days followed by a 10-day rest. Between October 1994 and March 1998, 18 patients were registered. The study was then closed because of poor accrual. Toxicity was moderate; three patients suffered from grade 3 anemia and one patient each had grade 3 thrombocytopenia, nausea/vomiting and grade 4 diarrhea. There was one partial response, seven with no change and 10 with progressive disease, yielding a response rate of 5.6%. The median progression-free survival and median survival time for the 18 patients were 55 and 164 days, respectively, with a 1-year survival rate of 5.6%. Although the number of patients was too small to draw any definitive conclusions, this study failed to demonstrate the survival advantage of doxifluridine.Japanese Journal of Clinical Oncology 04/2002; 32(3):90-4. · 1.78 Impact Factor
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2011
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Yamagata Prefectural Central Hospital
Yamagata-shi, Yamagata-ken, Japan
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2006–2011
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Aichi Cancer Center
Ōsaka-shi, Osaka-fu, Japan
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