S Negoro

Chiba-East National Hospital, Tiba, Chiba, Japan

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Publications (162)661.78 Total impact

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    ABSTRACT: We have conducted a phase 2 study to evaluate the efficacy and safety of carboplatin, paclitaxel, and bevacizumab in patients with non-squamous non-small-cell lung cancer (NSCLC) who are epidermal growth factor receptor (EGFR) mutation positive and for whom EGFR-tyrosine kinase inhibitor (TKI) 1st-line has failed.
    Lung Cancer. 12/2014;
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    ABSTRACT: Several trials have confirmed that the pathological complete response (pCR) rates after neoadjuvant chemotherapy (NAC) are significantly lower in HER2-positive/ER-positive patients than in HER2-positive/ER-negative patients. To understand this phenomenon, we investigated the association between NAC resistance and CCND1, which is frequently overexpressed in ER-positive tumors. Pretreatment formalin-fixed tumor tissues were collected from 75 HER2-positive patients receiving NAC comprised anthracyclines, taxanes, and trastuzumab. Seventeen gene transcripts along with PIK3CA mutations were detected using MassARRAY (Sequenom, San Diego, CA). The gene expression levels were dichotomized according to the median values. The immunohistochemical expression of ER, PTEN, BCL-2, and cyclin D1 was scored. The relationship between the variables was assessed using the Spearman correlation. A logistic regression analysis was performed to detect predictors of pCR, which was defined as no invasive tumor in the breast or axilla. Forty-seven percent of the cases were ER-positive and 52 % (40/63 % in ER-positive/ER-negative) achieved a pCR. Among the ER-positive patients, the CCND1 gene expression level was 2.1 times higher than that in ER-negative patients and was significantly correlated with the expression of cyclin D1 protein. In a univariate analysis, a pCR was associated with high mRNA levels of ESR1, PGR, LMTK3, HER2, IGF1R, INPP4B, PDL-1, BCL-2, and CCND1 (P ≤ 0.05). In contrast, none of these genes were significantly correlated with a pCR among the ER-negative tumors and only EGFR was significantly correlated with a pCR. PIK3CA mutations or PTEN loss were not associated with a pCR in either group. After excluding ESR1 (r = 0.58), PGR (r = 0.64), and IGF1R (r = 0.59), the expressions of which were correlated with CCND1, a multivariate analysis revealed that CCND1 [P = 0.043; OR, 0.16] and HER2 [P = 0.012; OR, 11.2] retained its predictive value for pCR among ER-positive patients, but not among ER-negative patients. A High Level of CCND1 gene expression is a poor predictor of a pCR and provides a rationale for evaluating CDK4/6 inhibitors in HER2-positive/ER-positive breast cancer patients.
    Breast Cancer Research and Treatment 09/2014; · 4.47 Impact Factor
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    ABSTRACT: Platinum agents are essential for treating gynecological malignancies, particularly ovarian cancer. However, multiple carboplatin doses may cause hypersensitivity reactions (HSRs). Carboplatin desensitization prevents life-threatening HSRs and promotes the successful completion of planned chemotherapy.
    International Journal of Clinical Oncology 07/2014; · 1.73 Impact Factor
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    ABSTRACT: We aimed to develop a more accurate model for predicting severe radiation pneumonitis (RP) after concurrent chemoradiotherapy for non-small-cell lung cancer.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2014; · 4.55 Impact Factor
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    ABSTRACT: Pemetrexed has relatively mild toxicity and possibly can be administered long term to patients with non-small-cell lung cancer. We conducted a Phase II trial to evaluate the efficacy and safety of pemetrexed in chemotherapy-naïve elderly patients with advanced non-squamous non-small-cell lung cancer. In this multicenter Phase II trial, we recruited elderly patients with non-squamous non-small-cell lung cancer. Patients with previously untreated Stage IIIB or IV non-squamous non-small-cell lung cancer, ≥75 years, Eastern Cooperative Oncology Group performance status 0-1 and adequate organ functions were eligible. Patients received pemetrexed (500 mg/m(2)) intravenously on Day 1 every 3 weeks until disease progression. The primary endpoint was objective response rate. Forty-seven patients were enrolled from August 2009 to July 2011, and 46 patients were eligible. The median age was 79 years (range 75-91 years), 57% were males, 37% had never smoked, 87% had adenocarcinoma, 74% had Stage IV and 33% had epidermal growth factor receptor tyrosine kinase-activating mutation. The median number of cycles was 4 (1-20). The objective response rate was 13.3% (95% confidence interval; 5.1-26.8%), the disease control rate was 66.7% (95% confidence interval 51.0-80.0%), the median progression-free survival was 4.9 months (95% confidence interval 3.0-6.1 months) and the median overall survival was 18.2 months (95% confidence interval 13.2-23.5 months). One Grade 5 infection (pneumonia) was observed. This study did not meet the primary endpoint. Pemetrexed monotherapy is not recommended in chemotherapy-naïve elderly patients aged ≥75 years with advanced non-squamous non-small-cell lung cancer.
    Japanese Journal of Clinical Oncology 10/2013; · 1.90 Impact Factor
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    ABSTRACT: Pemetrexed has shown substantial activity in non-squamous non-small cell lung cancer (NSCLC) and is one of the current standard agents in second-line settings due to its efficacy and favorable tolerability profile. We conducted phase II study to evaluate the safety and efficacy of pemetrexed in Japanese patients with previously heavily treated, advanced non-squamous NSCLC. Patients with stage IIIB or IV non-squamous NSCLC, performance status (PS) 0-2, previous two to five regimens of chemotherapy were enrolled and received pemetrexed (500 mg/m(2)) on day 1 every 21 days until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. From August 2009 to May 2010, 46 patients were enrolled: median age 65 years; 52 % women; PS 0/1/2 26/67/7 %; previous treatment regimen 2/3/4/5 48/28/20/4 %; epidermal growth factor receptor activating mutation positive/wild/unknown 30/48/22 %. The median follow-up period was 13.5 months. The median number of treatment cycles was 4 (range 1-18 cycles). The median PFS was 5.2 months (95 % CI 3.0-5.8 months). The median OS was 14.4 months (95 % CI 9.4-21.3 months). The ORR was 8.7 % and DCR was 63.0 %. The grade 3/4 hematological adverse events include 8 patients with leukopenia, 11 with neutropenia, 5 with anemia, and 2 with thrombocytopenia. There were no reports of febrile neutropenia and no treatment-related death was observed. Treatment with pemetrexed in previously heavily treated Japanese non-squamous NSCLC patients is feasible and shows encouraging activity.
    Cancer Chemotherapy and Pharmacology 10/2013; · 2.80 Impact Factor
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    ABSTRACT: Background:We evaluated the efficacy of aprepitant plus granisetron and an increased dose of dexamethasone in selected patients undergoing moderately emetogenic chemotherapy (MEC).Methods:Nondrinking women <70 years undergoing MEC were randomly assigned to aprepitant (day 1, 125 mg; days 2 and 3, 80 mg) or placebo. Dexamethasone on days 1-3 was 12, 4, and 4 mg with aprepitant and 20, 8, and 8 mg with placebo. The primary end point was complete response (CR; no emesis or rescue therapy) during 120 h of the first cycle. Logistic regression analysis was performed to identify predictors of overall CR.Results:Of the 94 patients enrolled, 91 were assessable. Most received carboplatin-based chemotherapy. In the aprepitant (n=45) and placebo (n=46) groups, the overall, acute (day 1), and delayed (days 2-5) CR rates were 62% and 52%, 98% and 96%, and 62% and 52%, respectively. Although not statistically significant, the overall CR rate was 10% higher in the aprepitant group. Both regimens were well tolerated. On multivariate analysis, advanced ovarian cancer (OR, 0.26 (0.10-0.72)) was independently associated with a lower CR.Conclusion:Even with an increased dose of dexamethasone, aprepitant seemed more effective than placebo in these selected patients undergoing MEC; however, delayed phase management remains a significant problem.British Journal of Cancer advance online publication, 16 July 2013; doi:10.1038/bjc.2013.400 www.bjcancer.com.
    British Journal of Cancer 07/2013; · 5.08 Impact Factor
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    ABSTRACT: BACKGROUND: A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S-1 (an oral fluoropyrimidine) and carboplatin compared with combined paclitaxel and carboplatin as first-line treatment for advanced non-small cell lung cancer (NSCLC). In the current study, the authors evaluated the efficacy and safety of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab in chemotherapy-naive patients with advanced nonsquamous NSCLC. METHODS: Patients received carboplatin (area under the concentration-time curve, 5 mg mL(-1) per minute) and bevacizumab (15 mg/kg) on day 1 plus oral S-1 (80 mg/m(2) per day) on days 1 through 14 every 21 days for up to 6 cycles. For patients without disease progression, S-1 and bevacizumab were continued until disease progression or unacceptable toxicity developed. RESULTS: Forty-eight patients were enrolled in the phase 2 study; of these, 35 patients (72.9%) completed at least 4 cycles. Most toxicities of grade ≥3 were hematologic, and no increase in relative incidence associated with maintenance with S-1 and bevacizumab was observed. The objective response rate was 54.2% (95% confidence interval, 39.2%-68.6%), and the median progression-free survival was 6.8 months (95% confidence interval, 4.3-8.2 months). CONCLUSIONS: The regimen of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab was active and feasible as first-line treatment for advanced nonsquamous NSCLC. Cancer 2013. © 2013 American Cancer Society.
    Cancer 04/2013; · 5.20 Impact Factor
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    ABSTRACT: PURPOSE: In a large multicenter international phase III study (CA031) of nab-paclitaxel (nab-P, 130nm albumin-bound paclitaxel particles)+carboplatin (C) vs solvent-based paclitaxel (sb-P)+C, conducted in 6 countries including Japan, nab-PC produced significantly higher overall response rate (ORR), primary end point compared with sb-PC, and acceptable safety profile. The aim of this analysis was to evaluate the efficacy and tolerability of nab-PC vs sb-PC in Japanese patients with advanced non-small-cell lung cancer (NSCLC) who were enrolled in the CA031 study. PATIENTS AND METHODS: In the CA031 study, a total of 1052 patients were randomized to receive either nab-P 100mg/m(2) weekly or sb-P 200mg/m(2) every 3 weeks both in combination with C at area under the concentration-time curve (AUC)=6 on day 1 of each 3-week cycle. This analysis included 149 Japanese patients with previously untreated stage IIIB or IV NSCLC. RESULTS: The baseline and histologic characteristics of patients were well balanced between the two arms. ORR was higher with nab-PC vs sb-PC (35% vs 27%; response rate ratio=1.318). Progression-free survival (median 6.9 vs 5.6 months; hazard ratio [HR]=0.845) and overall survival (median 16.7 vs 15.9 months; HR=0.930) were better with nab-PC vs sb-PC. Of the grade ≥3 treatment-related adverse events, anemia and thrombocytopenia were more common in nab-PC arm, but sensory neuropathy was less common. CONCLUSION: The nab-PC treatment yielded promising results regarding the efficacy endpoint, and it was generally well tolerated as first-line therapy for Japanese patients with advanced NSCLC.
    Lung cancer (Amsterdam, Netherlands) 03/2013; · 3.14 Impact Factor
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    ABSTRACT: Background Four cycles of etoposide plus cisplatin and accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard of care for limited-stage small-cell lung cancer (SCLC). Irinotecan plus cisplatin significantly improved overall survival compared with etoposide plus cisplatin for extensive-stage SCLC. We compared these regimens for overall survival of patients with limited-stage SCLC. Methods We did this phase 3 study in 36 institutions in Japan. Eligibility criteria included age 20–70 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and adequate organ functions. Eligible patients with previously untreated limited-stage SCLC received one cycle of etoposide plus cisplatin (intravenous etoposide 100 mg/m2 on days 1–3; intravenous cisplatin 80 mg/m2 on day 1) plus AHTRT (1·5 Gy twice daily, 5 days a week, total 45 Gy over 3 weeks). Patients without progressive disease following induction therapy were randomised (1:1 ratio, using a minimisation method with biased-coin assignment balancing on ECOG performance status [0 vs 1], response to induction chemoradiotherapy [complete response plus near complete response vs partial response and stable disease], and institution) to receive either three further cycles of consolidation etoposide plus cisplatin or irinotecan plus cisplatin (intravenous irinotecan 60 mg/m2 on days 1, 8, 15; intravenous cisplatin 60 mg/m2 on day 1). Patients, physicians, and investigators were aware of allocation. The primary endpoint was overall survival after randomisation; primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00144989, and the UMIN Clinical Trials Registry, number C000000095. Findings 281 patients were enrolled between Sept 1, 2002, and Oct 2, 2006. After induction etoposide plus cisplatin and AHTRT, 258 patients were randomised to consolidation etoposide plus cisplatin (n=129) or irinotecan plus cisplatin (n=129). In the etoposide plus cisplatin group, median overall survival was 3·2 years (95% CI 2·4–4·1). In the irinotecan and cisplatin group, median overall survival was 2·8 years (95% CI 2·4–3·6); overall survival did not differ between the two groups (hazard ratio 1·09 [95% CI 0·80–1·46], one-sided stratified log-rank p=0·70). The most common adverse events of grade 3 or 4 were neutropenia (120 [95%] in the etoposide plus cisplatin group vs 101 [78%] in the irinotecan plus cisplatin group), anaemia (44 [35%] vs 50 [39%]), thrombocytopenia (26 [21%] vs six [5%]), febrile neutropenia (21 [17%] vs 18 [14%]), and diarrhoea (two [2%] vs 13 [10%]). There was one treatment-related adverse event leading to death in each group (radiation pneumonitis in the etoposide plus cisplatin group; brain infarction in the irinotecan plus cisplatin group). Interpretation Four cycles of etoposide plus cisplatin and AHTRT should continue to be the standard of care for limited-stage SCLC. Funding National Cancer Center and the Ministry of Health, Labour, and Welfare of Japan.
    The Lancet Oncology 01/2013; · 25.12 Impact Factor
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    ABSTRACT: This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safety of first-line carboplatin-paclitaxel (CP) alone with bevacizumab-CP in Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Chemonaïve patients with stage IIIB, IV or recurrent non-squamous NSCLC were eligible for participation. Patients were randomly assigned in a 2:1 ratio to receive bevacizumab-CP or CP alone. Chemotherapy was repeated for up to 6 cycles or until disease progression or unacceptable toxicity. Bevacizumab recipients who completed ≥3 cycles of chemotherapy could continue bevacizumab as monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). After confirming the tolerability of bevacizumab-CP in a small number of patients, 180 patients were recruited, of whom 121 were assigned to bevacizumab-CP and 59 to CP alone. Hazard ratio (HR) for PFS was 0.61 with bevacizumab-CP versus CP alone (p=0.0090; median 6.9 versus 5.9 months). Objective response rate was significantly higher with bevacizumab-CP than with CP alone (60.7% versus 31.0%; p=0.0013). Median overall survival was >22 months in both treatment groups (HR 0.99; p=0.9526). No new safety signals were detected. Study JO19907 met its primary endpoint, demonstrating that the addition of bevacizumab to first-line CP significantly improves PFS in Japanese patients with advanced non-squamous NSCLC. This prolonged PFS by bevacizumab did not translate into OS benefit with the extremely longer underlying survival compared to historical data. No new safety signals were identified in this population. (Japan Pharmaceutical Information Center [JAPIC] registration number: CTI-060338).
    Lung cancer (Amsterdam, Netherlands) 01/2012; 76(3):362-7. · 3.14 Impact Factor
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    ABSTRACT: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m(2)) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m(2)). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade ≥4 esophagitis and neutropenic fever and Grade ≥3 other nonhematologic toxicities, was monitored for 90 days. Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.
    International journal of radiation oncology, biology, physics 11/2011; 83(1):327-31. · 4.59 Impact Factor
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    ABSTRACT: Evaluation of health-related quality-of-life (HRQoL) and symptom improvement were preplanned secondary objectives for the overall population and posthoc analyses for epidermal growth factor receptor (EGFR) mutation-positive/negative subgroups in IPASS. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) and Trial Outcome Index (TOI); symptom improvement by the Lung Cancer Subscale (LCS). Improvements defined as: 6 or more (FACT-L; TOI), 2 or more (LCS) points increase maintained for 21 or more days. Overall (n = 1151/1217 evaluable), HRQoL improvement rates were significantly greater with gefitinib versus carboplatin/paclitaxel; symptom improvement rates were similar for both treatments. Significantly more patients recorded improvements in HRQoL and symptoms with gefitinib in the EGFR mutation-positive subgroup (n = 259; FACT-L 70.2% versus 44.5%; odds ratio, 3.01 [95% confidence interval, 1.79-5.07]; p < 0.001; TOI 70.2% versus 38.3%; 3.96 [2.33-6.71]; p < 0.001; LCS 75.6% versus 53.9%; 2.70 [1.58-4.62]; p < 0.001), and with carboplatin/paclitaxel in the EGFR mutation-negative subgroup (n = 169; FACT-L 14.6% versus 36.3%; odds ratio, 0.31 [0.15-0.65]; p = 0.002; TOI 12.4% versus 28.8%; 0.35 [0.16-0.79]; p = 0.011; LCS 20.2% versus 47.5%; 0.28 [0.14-0.55]; p < 0.001). Median time-to-worsening (months) FACT-L score was longer with gefitinib versus carboplatin/paclitaxel for the overall population (8.3 versus 2.5) and EGFR mutation-positive subgroup (15.6 versus 3.0), and similar for both treatments in the EGFR mutation-negative subgroup (1.4 versus 1.4). Median time-to-improvement with gefitinib was 8 days in patients with EGFR mutation-positive tumors who improved. HRQoL and symptom endpoints were consistent with efficacy outcomes in IPASS and favored gefitinib in patients with EGFR mutation-positive tumors and carboplatin/paclitaxel in patients with EGFR mutation-negative tumors.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2011; 6(11):1872-80. · 4.55 Impact Factor
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    ABSTRACT: Continuous erythropoietin receptor activator (C.E.R.A.) is an innovative erythropoiesis-stimulating agent with unique erythropoietin receptor activity and a prolonged half-life. C.E.R.A. is currently in development for the correction of anemia and stable hemoglobin (Hb) control at extended administration intervals in patients with cancer who are receiving chemotherapy. The purpose of this pharmacological study was to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) and safety profiles of C.E.R.A. administered subcutaneously once every 3 weeks (Q3W) in lung cancer patients with anemia induced by chemotherapy. This open-label, multicenter study recruited 46 patients. Entry Hb levels were not more than 11.0 g/dl. Five dose levels of C.E.R.A. (2.1, 4.2, 6.3, 9 and 12 μg/kg) were tested in sequential cohorts of 8-11 patients for 12 weeks. The mean values for C.E.R.A half-life ranged from 143 to 247 h. The maximum serum concentration (C(max)) following the first administration of C.E.R.A. increased in proportion to the dose. The increase of Hb levels occurred in a dose-dependent manner. No serious adverse events reported as being related to C.E.R.A. were observed during the study period. Thrombovascular events were not observed in any patient. Anti-C.E.R.A antibodies were not detected in any patient. Thus, this pharmacological study confirmed the long half-life of C.E.R.A., thereby supporting subcutaneous administration of C.E.R.A. at the Q3W interval. PK and PD parameters demonstrated dose-proportionality over the range of doses tested in this study. Additionally, C.E.R.A. was generally well tolerated.
    Oncology letters 11/2011; 2(6):1033-1040. · 0.24 Impact Factor
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    ABSTRACT: In IPASS (IRESSA Pan-Asia Study), clinically selected patients with pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel. This preplanned, exploratory analysis was conducted to increase understanding of the use of surrogate samples, such as serum, versus tumor biopsy samples for determining EGFR mutation status in the Japanese cohort (n = 233). EGFR mutations were assessed using tumor tissue-derived DNA (n = 91) and circulating free (cf) DNA from pretreatment serum samples (n = 194). Fewer patients were EGFR mutation positive when assessed using pretreatment cfDNA (23.7%) versus tumor tissue-derived DNA (61.5%). cfDNA results identified no false positives but a high rate of false negatives (56.9%). There was a significant interaction between cfDNA EGFR mutation status and treatment for progression-free survival (PFS) (p = 0.045). PFS was significantly longer and objective response rate (ORR) higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation-positive subgroup (PFS: hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.14-0.60; p < 0.001; ORR: odds ratio [OR], 1.71; 95% CI, 0.48-6.09; 75.0% versus 63.6%; p = 0.40). There was a slight numerical advantage in PFS and ORR for gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative subgroup, likely due to the high rate of false negatives within this subgroup. These results merit further investigation to determine whether alternative sources of tumor DNA, such as cfDNA in serum, could be used for determining EGFR mutation status in future; currently, where a sample is available, analysis of tumor material is recommended.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2011; 7(1):115-21. · 4.55 Impact Factor
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    ABSTRACT: We conducted a phase I trial of BNP7787 (disodium 2,2'-dithio-bis-ethane sulfonate, Tavocept™), a novel chemoprotective and antitumor enhancing agent administered in combination with paclitaxel and cisplatin. The primary aim was to determine a safe and potentially efficacious BNP7787 dose for preventing and mitigating paclitaxel- and cisplatin-induced toxicities and to evaluate for preliminary evidence of efficacy of treatment. Twenty-two patients with stage IIIB/IV non-small cell lung cancer (NSCLC) received BNP7787 alone 1 week before co-administration of BNP7787 with paclitaxel followed by cisplatin. Twenty-one patients were treated with BNP7787 in escalating doses of 4.1-41.0 g/m² concurrently with paclitaxel 175 mg/m² and cisplatin 75 mg/m² every 3 weeks. The appropriate dose was determined to be 18.4 g/m² of BNP7787 although no dose-limiting toxicity was observed up to 41.0 g/m². Mild intravenous site discomfort, thirst, and nausea were the most common toxicities. One patient developed grade 2 skin rash, which was severe enough to preclude further study treatment. The AUC(0-inf) of the metabolite mesna was approximately 6.3% of the AUC(0-inf) of BNP7787. Co-administration of paclitaxel and cisplatin did not appear to influence the pharmacokinetics of BNP7787 and mesna. The overall response rate was encouraging; 43% including 11 patients with prior chemotherapy. The recommended dose for phase II/III studies is 18.4 mg/m² of BNP7787 in combination with paclitaxel and cisplatin. Further studies are warranted to assess whether BNP7787 prevents and mitigates common and serious paclitaxel- and cisplatin-related side effects and enhances the efficacy of paclitaxel and cisplatin in advanced NSCLC patients.
    Cancer Chemotherapy and Pharmacology 03/2011; 67(3):533-42. · 2.80 Impact Factor
  • European Journal of Cancer - EUR J CANCER. 01/2011; 47.
  • European Journal of Cancer - EUR J CANCER. 01/2011; 47.
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    ABSTRACT: It is important to identify optimal regimens of cisplatin-based, third-generation chemotherapy and thoracic radiotherapy for patients with unresectable, Stage III, non-small cell lung cancer. Patients with unresectable, Stage III non-small cell lung cancer were treated with the following regimen: cisplatin 80 mg/m(2) on days 1 and 29, with irinotecan 60 mg/m(2) on days 1, 8, 15, 29, 36, and 43 and 30 mg/m(2) on days 57, 64, 71, 78, 85 and 92. Thoracic radiotherapy was started on day 57 at 2 Gy/day (total 60 Gy). From February 1998 to January 1999, 68 patients were enrolled. Grade 3/4 toxicities during induction chemotherapy primarily included neutropenia (73.5%) and diarrhea (20.6%), while Grade 3/4 toxicities during concomitant thoracic radiotherapy with irinotecan consisted of neutropenia (18.4%), esophagitis (4.1%) and hypoxia (6.5%). There was one treatment-related death due to radiation pneumonitis. The response rate was 64.7% (95% confidence interval, 52.2-75.9%). The median survival time was 16.5 (95% confidence interval, 12.6-19.8) months. The 1- and 2 year survival rates were 65.8% (95% confidence interval, 54.4-77.1%) and 32.9% (95% confidence interval, 21.6-44.1%), respectively. Overall, only 36 (56%) completed both the scheduled chemotherapy and thoracic radiotherapy. Induction chemotherapy with cisplatin plus irinotecan followed by low-dose irinotecan and concomitant thoracic radiotherapy was feasible according to the prespecified decision criteria in this study for patients with unresectable Stage III non-small cell lung cancer. We did not decide to select this regimen for further investigations because approximately half of the patients completed the scheduled treatment.
    Japanese Journal of Clinical Oncology 01/2011; 41(1):25-31. · 1.90 Impact Factor
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    ABSTRACT: We conducted a phase I trial of the topoisomerase I inhibitor topotecan for the purpose of determining the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of topotecan when administered weekly to patients with advanced non-small-cell lung cancer. Twelve patients with stage IIIB or IV disease were treated with topotecan by 30-minute intravenous infusion on days 1, 8, and 15 every 4 weeks. The dose was escalated in 2-mg/m2 increments from the starting dose of 4 mg/m2 until the MTD was reached. After the MTD had been reached in previously treated patients, chemotherapy-naive patients were enrolled for treatment at that dose, and the dose was escalated to estimate the MTD in the treatment-naive group. The MTD of topotecan was determined to be 6 mg/m2 in the previously treated group and 8 mg/m2 in the chemotherapy-naive group. All 3 previously treated patients experienced DLT at the 6-mg/m2 dose level. Although only 1 of the 3 previously treated patients experienced DLT (grade 4 neutropenia for > or = 3 days) at the 8-mg/m2 dose level, skipping the topotecan dose on day 15 because of neutropenia was reported in 2 patients. Anorexia and general fatigue were the common nonhematologic toxicities. The recommended dose of topotecan for phase II studies in previously untreated patients is 6 mg/m2 on days 1, 8, and 15, every 28 days, and 4 mg/m2 appears to be a suitable dose for use in previously treated patients with this schedule.
    Clinical Lung Cancer 07/2010; 11(4):271-9. · 2.04 Impact Factor

Publication Stats

4k Citations
661.78 Total Impact Points

Institutions

  • 2011–2012
    • Chiba-East National Hospital
      Tiba, Chiba, Japan
    • Chiang Mai University
      • Faculty of Medicine
      Chiang Mai, Chiang Mai Province, Thailand
  • 2008–2012
    • Hyogo Cancer Center
      Akasi, Hyōgo, Japan
  • 2010–2011
    • Kitasato University
      • Department of Respiratory Medicine
      Edo, Tōkyō, Japan
    • Shizuoka Cancer Center
      Sizuoka, Shizuoka, Japan
  • 1995–2011
    • Osaka City General Hospital
      Ōsaka, Ōsaka, Japan
  • 2005–2009
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 2000–2009
    • National Cancer Center, Japan
      • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
    • National Hospital Organization Sagamihara Hospital
      Sagamihara, Kanagawa, Japan
  • 2007
    • Otemae Hospital
      Ōsaka, Ōsaka, Japan
  • 2000–2007
    • Kinki University
      • • Department of Radiation Oncology
      • • Faculty of Medicine
      • • Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 2002–2006
    • Osaka City University
      • First Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
    • Kanagawa Cancer Center
      Yokohama, Kanagawa, Japan
  • 1995–2004
    • Kobe City Medical Center General Hospital
      Kōbe, Hyōgo, Japan
  • 1998
    • Rinku General Medical Center
      Ōsaka, Ōsaka, Japan
  • 1996–1997
    • Osaka Central Hospital
      • Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 1994
    • Niigata Cancer Center Hospital
      Niahi-niigata, Niigata, Japan