Minoru Takada

Wakayama Medical University, Wakayama, Wakayama, Japan

Are you Minoru Takada?

Claim your profile

Publications (210)789.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Univariate analyses from several randomized phase III trials seemed to suggest ever-smokers with advanced mutated epidermal growth factor receptor (EGFRm) non-small-cell lung cancer (NSCLC) did not seem to benefit from EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment when compared with platinum-doublet chemotherapy as measured by progression-free survival (PFS). A literature-based meta-analysis of PFS outcomes as measured by log-transformed pooled hazard ratio (HR) was performed using a random-effect model. Pooled HRs for smoking status, age, gender, ethnicity, type of EGFR mutation, and EGFR TKI were obtained. Comparison of the pooled HR was performed by metaregression analysis. Among the 1,649 EGFRm NSCLC patients analyzed from 7 prospective randomized trials (WJTOG3405, NEJ002, EURTAC, OPTIMAL, LUX Lung-3, LUX Lung-6, and ENSURE), 83.7% were Asians, and 30.0% were ever-smokers. An equal percentage of ever-smokers received doublet chemotherapy (30.2%) or EGFR TKI (30.0%). The pooled HR for PFS was 0.29 (95% confidence interval [CI]: 0.21-0.39) for never-smokers and 0.54 (95% CI: 0.38-0.76) for ever-smokers (p < .007 by metaregression). The pooled PFS HR for exon 19 deletion was 0.25 (95% CI: 0.19-0.31) and 0.44 for exon 21 substitution (95% CI: 0.34-0.57) (p < .001 by metaregression analysis). The pooled PFS HR was 0.33 (95% CI: 0.24-0.46) for Asians and 0.48 for non-Asians (95% CI: 0.28-0.84) (p = .261 by metaregression analysis). EGFRm NSCLC patients derived significant PFS benefit from TKI over platinum-doublet chemotherapy as first-line treatment regardless of smoking status; however, PFS benefit is significantly better in never-smokers by metaregression analysis. ©AlphaMed Press.
    The Oncologist 02/2015; 20(3). DOI:10.1634/theoncologist.2014-0285 · 4.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 47-year-old man was referred to our department due to multiple metastases in the lungs and liver with pleural dissemination six weeks after undergoing curative surgery for lung pleomorphic carcinoma. He received two regimens of chemotherapy, both of which resulted in disease progression. Considering his good general condition, he was treated with cisplatin plus gemcitabine (GP). The metastatic lesions exhibited a complete response after six courses of GP, and the patient has remained free from recurrence for over six years. An immunohistochemical analysis revealed that the tumor was highly expressive of gemcitabine transporter human equilibrative nucleoside transporter 1, thus suggesting a high sensitivity to gemcitabine.
    Internal Medicine 11/2014; 53(22):2625-8. DOI:10.2169/internalmedicine.53.2637 · 0.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To investigate the efficacy of erlotinib versus docetaxel in previously treated patients with advanced non-small-cell lung cancer (NSCLC) in an epidermal growth factor receptor (EGFR) -unselected patient population. Patients and methods: The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), response rate, safety, and analyses on EGFR wild-type tumors. Patients with stage IIIB or IV NSCLC, previous treatment with one or two chemotherapy regimens, evaluable or measurable disease, and performance status of 0 to 2 were eligible. Results: From August 2009 to July 2012, 150 and 151 patients were randomly assigned to erlotinib (150 mg daily) and docetaxel (60 mg/m(2) every 3 weeks), respectively. EGFR wild-type NSCLC was present in 109 and 90 patients in the erlotinib and docetaxel groups, respectively. Median PFS for erlotinib versus docetaxel was 2.0 v 3.2 months (hazard ratio [HR], 1.22; 95% CI, 0.97 to 1.55; P = .09), and median OS was 14.8 v 12.2 months (HR, 0.91; 95% CI, 0.68 to 1.22; P = .53), respectively. In a subset analysis of EGFR wild-type tumors, PFS for erlotinib versus docetaxel was 1.3 v 2.9 months (HR, 1.45; 95% CI, 1.09 to 1.94; P = .01), and OS was 9.0 v 10.1 months (HR, 0.98; 95% CI, 0.69 to 1.39; P = .91), respectively. Conclusion: Erlotinib failed to show an improvement in PFS or OS compared with docetaxel in an EGFR-unselected patient population.
    Journal of Clinical Oncology 05/2014; 32(18). DOI:10.1200/JCO.2013.52.4694 · 18.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Early prediction of therapeutic outcome is important in determining whether the ongoing therapy is beneficial. In addition to anatomical response as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, recent studies have indicated that change in tumor glucose use on or after treatment correlates with histopathologic tumor regression and patient outcomes. This Perspective discusses the use of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) for pharmacodynamic evaluation in a very early phase of treatment to predict clinical outcomes in patients with advanced non-small cell lung cancer. We conducted a study to assess whether early metabolic response determined by FDG-PET correlated with clinical outcomes in patients treated with gefitinib or those treated with carboplatin plus paclitaxel (CP). Early metabolic response to gefitinib, but not CP, correlated with the late metabolic response, anatomical response, progression-free survival and even overall survival. A rapid effect of molecular targeted agents may not be aptly evaluated by the conventional criteria, e.g., RECIST, in a very early phase of treatment before volumetric shrinkage of the tumor. Based on the findings of several studies, as well as the findings from our study, use of FDG-PET might enable prediction of clinical outcomes at a very early stage of treatment, especially in patients treated with molecular targeted agents with rapid clinical efficacy.
    Clinical Lung Cancer 05/2014; 15(3). DOI:10.1016/j.cllc.2014.01.001 · 3.10 Impact Factor
  • Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2014; 9(1):e7-e8. DOI:10.1097/JTO.0000000000000035 · 5.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Non-small cell lung cancer (NSCLC) in never smokers has emerged as a global public health issue. The cause is still unclear, and few studies have focused on the prevalence of human papillomavirus (HPV) in the never smokers. We performed a systematic search of PubMed for articles of HPV infection in human subjects with NSCLC up to September 2012. Although smoking status was not fully reported in all studies, we contacted the authors by e-mail to supplement this information. Differences in the distribution of patients with and without HPV infection were tested with the Chi squared test. We identified 46 eligible articles, including 23 from Asian countries (N=2337 NSCLC cases), 19 from European countries (N=1553) and 4 from North and South America (N=160). The HPV prevalence was 28.1% (95% confidence interval (CI) 26.6-30.3%), 8.4% (95% CI 7.1-9.9%) and 21.3% (95% CI 15.2-28.4%), respectively. Eleven studies from East Asia (N=1110) and 4 from Europe (N=569) provided information on smoking status. The number of never smoker was 392 patients (33.9%) in East Asia and 54 patients (14.8%) in Europe. The HPV prevalence in East Asian countries was similar between never and ever smokers (33.9% vs 39.2%, P=0.080). Based on the literature confirming the presence of HPV in lung cancer in never smokers, the virus plays a role in carcinogenesis in the disease. There were different patterns of HPV prevalence between Asian and European countries in the never smokers as well as in ever smokers.
    Lung cancer (Amsterdam, Netherlands) 10/2013; 83(1). DOI:10.1016/j.lungcan.2013.10.002 · 3.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to evaluate whether consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy is beneficial for patients with locally advanced non-small-cell lung cancer (LA-NSCLC). We systematically searched PubMed for phase II/III trials published before December 31, 2011, examining survival of LA-NSCLC treated with concurrent chemo-radiotherapy. Median overall survival and other study characteristics were collected from each study and pooled. We extracted log-transformed hazards and standard errors under the assumption that survival follows an exponential distribution, and computed a pooled median overall survival and a 95% confidence interval (CI) using random-effects model. Collected trial arms were categorized as having CCT or not having it, CCT+ and CCT-, respectively. Forty-one studies were identified including seven phase III studies and 34 phase II studies with 45 arms (CCT+: 25; CCT-: 20). Clinical data were comparable for clinical stage, performance status, cancer histology, sex, and median age between the two groups. There was no statistical difference in pooled mOS between CCT+ (19.0 month; 95% CI, 17.3-21.0) and CCT- (17.9 month; 95% CI, 16.1-19.9). Predicted hazard ratio of CCT+ to CCT- was 0.94 (95% CI, 0.81-1.09; p = 0.40). There were no differences between the two groups with regard to grade 3-5 toxicities in pneumonitis, esophagitis, and neutropenia. These models estimated that addition of CCT could not lead to significant survival prolongation or risk reduction in death for LA-NSCLC patients. The pooled analysis based on a publication basis failed to provide evidence that CCT yields significant survival benefit for LA-NSCLC.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2013; 8(9). DOI:10.1097/JTO.0b013e3182988348 · 5.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The epidermal growth factor receptor (EGFR) gene is highly polymorphic and its expression and activity may be affected by various polymorphisms. There have been several studies examining associations between EGFR polymorphisms and clinical outcome of lung cancer therapy; however, the underlying mechanism is largely unknown. The present study investigated EGFR polymorphism status and its correlation with clinicopathological features in Japanese non-small cell lung cancer (NSCLC) patients. We investigated 5 polymorphisms in the EGFR gene (-216G/T, -191C/A, 8227G/A, D994D and R497K) in 274 surgically-treated NSCLC patients. TaqMan single nucleotide polymorphism (SNP) genotyping assays and a PCR-based assay were used to analyze these polymorphisms. In our cohort of patients we did not find any evidence of the -191C/A polymorphism. Our results showed that the patients with the 8227GA or AA type in intron 1 had a significantly better prognosis with the anti-EGFR therapy than the patients with the GG type (p=0.0448) in terms of recurrence of lung cancer. No significant association was observed between 3 other SNPs (-216G/T, D994D and R497K) and clinicopathological features. The EGFR 8227G/A polymorphism in intron 1 may be associated with clinical outcome in NSCLC patients treated with EGFR tyrosine kinase inhibitors.
    Experimental and therapeutic medicine 11/2012; 4(5):785-789. DOI:10.3892/etm.2012.681 · 1.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: : It is not determined whether the continuous use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is reasonable for patients with activating EGFR mutations, who have progressed with the drug. : We retrospectively analyzed the data from 2002 to 2010 of consecutive patients who had advanced non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations and showed radiological disease progression after EGFR-TKI treatment as the first-line or second-line setting. We classified them into two groups: continuous EGFR-TKI and switching to chemotherapy, and compared the clinical outcomes. Multivariate analysis for survival was performed including age, sex, Eastern Cooperative Oncology Group performance status (0-1/ 2-4), brain metastasis, EGFR mutations (deletions in exon 19 versus L858R), continuous EGFR-TKI (yes/no), and initiation of EGFR-TKI (first versus second). : A total of 551 NSCLC patients were screened for EGFR mutations in the period, and 186 patients had activating EGFR mutations. To explore the potential use of EGFR-TKI beyond progressive disease (PD), 64 patients were selected and analyzed. There were 13 men and 51 women, and median age was 65.5 years (range, 42-86). Among them, 31 patients had deletions in exon 19, and 33 had point mutation of L858R in exon 21. Thirty-nine patients were continuing EGFR-TKI beyond PD; 25 patients were switched to cytotoxic chemotherapy alone. The median overall survival was 32.2 months in the patients continuing EGFR-TKI, and 23.0 months in the patients switching to chemotherapy, presenting a significant difference between the two groups (p = 0.005). Cox analysis showed that continuous EGFR-TKI after PD (hazards ratio 0.42, 95% confidence interval: 0.21-0.83, p = 0.013) was associated with improved survival. : Continuous use of EGFR-TKI beyond PD may prolong overall survival compared with switching to cytotoxic chemotherapy in patients with activating EGFR mutations. A prospective study will be needed to confirm our results.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(11):1722-7. DOI:10.1097/JTO.0b013e31826913f7 · 5.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the efficacy and feasibility of the consolidation therapy of the oral fluoropyrimidine agent S-1 after concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer (NSCLC). Eligible patients had unresectable stage III NSCLC with performance status of 0 or 1. Chemoradiotherapy at a total dose of 60 Gy consisted of cisplatin (80 mg/m(2)) on days 1 and 29, vinorelbine (20 mg/m(2)) on days 1, 8, 29 and 36. Sequential consolidation S-1 therapy was commenced at a dose of 80-120 mg twice daily on day 57 with two cycles of 4 weeks administration and 2 weeks withdrawal. Of the 66 patients, 65 were evaluated. Chemoradiotherapy was completed in 57 (87.7%) patients, and S-1 consolidation therapy was administered in 45 (69.2%) and completed in 31 (47.6%). Grade 3 pneumonitis developed in three patients with one dying of it. The response rate was 61.5% (95% confidence interval [CI], 48.6-73.3%). The median progression-free survival was 10.2 (95%CI, 8.6-13.7) months and median survival time 21.8 (95%CI, 15.6-27.6) months. The 1- and 3-year survival rates were 73.9% and 34.0%, respectively. Chemoradiotherapy with cisplatin and vinorelbine followed by S-1 consolidation demonstrated a reasonable overall survival in patients with stage III NSCLC. However, less than half of the patients completed this regimen, and the additional effect of S-1 was marginal compared with historical control. We concluded that chemoradiotherapy alone is still the recommended standard treatment for patients.
    European journal of cancer (Oxford, England: 1990) 12/2011; 48(5):672-7. DOI:10.1016/j.ejca.2011.11.020 · 5.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cetuximab, an antibody directed against the epidermal growth factor receptor, is an effective clinical therapy for patients with colorectal, head and neck, and non-small cell lung cancer, particularly for those with KRAS and BRAF wild-type cancers. Treatment in all patients is limited eventually by the development of acquired resistance, but little is known about the underlying mechanism. Here, we show that activation of ERBB2 signaling in cell lines, either through ERBB2 amplification or through heregulin up-regulation, leads to persistent extracellular signal-regulated kinase 1/2 signaling and consequently to cetuximab resistance. Inhibition of ERBB2 or disruption of ERBB2/ERBB3 heterodimerization restores cetuximab sensitivity in vitro and in vivo. A subset of colorectal cancer patients who exhibit either de novo or acquired resistance to cetuximab-based therapy has ERBB2 amplification or high levels of circulating heregulin. Collectively, these findings identify two distinct resistance mechanisms, both of which promote aberrant ERBB2 signaling, that mediate cetuximab resistance. Moreover, these results suggest that ERBB2 inhibitors, in combination with cetuximab, represent a rational therapeutic strategy that should be assessed in patients with cetuximab-resistant cancers.
    Science translational medicine 09/2011; 3(99):99ra86. DOI:10.1126/scitranslmed.3002442 · 15.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are a large number of global clinical trials ongoing for patients with non-small cell lung cancer (NSCLC). Ethnic difference in toxicity has not been adequately studied. We performed a systematic search in PubMed for randomized phase II and III trials of NSCLC from January 2000 to December 2009, examining ethnic difference in hematological toxicity due to cytotoxic chemotherapy. Ethnicity was classified into Asian and non-Asian. We chose three treatment regimens used for NSCLC globally: cisplatin plus gemcitabine (CG), cisplatin plus vinorelbine (CV), and carboplatin plus paclitaxel (CP). We applied sensitivity analysis to examine unreported ethnic differences in hematological toxicities by changing the percentage of Asian patients from 0 to 18% in trials reported from the United States and Europe. We identified 12 phase II trials and 38 phase III trials of NSCLC with a total of 11,271 patients. Among these, 14 trials had reported ethnic origins. Grade 3/4 toxicities were more frequently observed in the Asian studies. On the basis of sensitivity analysis, odds ratio of grade 3/4 neutropenia was significantly higher in Asian patients than non-Asian, when treated with CG (OR = 1.55-3.45, p < 0.001), CV (OR = 2.99-4.43, p < 0.001), and CP (OR = 4.79-6.22, p < 0.001). Grade 3/4 anemia was also significantly higher in Asians with CG (OR = 3.10-3.27, p < 0.001), CV (OR = 1.99-2.43, p < 0.001), and CP (OR = 1.34-1.52, p < 0.001-0.004). However, no significant difference was observed in thrombocytopenia with CG (OR = 0.66-2.04, p < 0.001-1.000), CV (OR = 0.42-0.57, p = 0.097-0.323), or CP (OR = 1.21-1.39, p = 0.114-0.152). Severe hematological toxicity was frequently observed in Asian patients compared with non-Asian (mostly whites) in the treatment of chemotherapy for NSCLC.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2011; 6(11):1881-8. DOI:10.1097/JTO.0b013e31822722b6 · 5.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Elderly patients prefer to receive less-toxic therapy. Monotherapy using drugs such as vinorelbine, gemcitabine or docetaxel is a preferable chemotherapy in elderly patients with advanced non-small-cell lung cancer. Gefitinib shows remarkable efficacy in patients with advanced non-small-cell lung cancer, who have activating epidermal growth factor receptor mutations. Adenocarcinoma histology is related to these mutations. Therefore, we conducted a phase II study of gefitinib as a first-line therapy in elderly patients with pulmonary adenocarcinoma. Eligible patients were 70 years or older, had pulmonary adenocarcinoma, stage IIIB or IV disease, an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ functions. Patients were treated with oral gefitinib 250 mg daily until disease progression or unacceptable toxicity. Thirty-one patients were enrolled, of whom 30 were eligible. The median age was 78.5 years. The response rate was 20%, the disease control rate was 47%, the median progression-free survival was 2.7 months and the median overall survival was 11.9 months. Narrowing it down to those who had never smoked, the response rate increased to 43%, the disease control rate increased to 57%, the median progression-free survival prolonged to 7.1 months and the median overall survival prolonged to 13.0 months. The most frequent toxicity was rash. Other major toxicities were diarrhea, anorexia, liver dysfunction and anemia. These toxicities were mild and easily managed. Gefitinib as a first-line therapy is active and well tolerated in elderly patients with pulmonary adenocarcinoma, especially in those who have never smoked.
    Japanese Journal of Clinical Oncology 06/2011; 41(8):948-52. DOI:10.1093/jjco/hyr087 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small-cell lung cancer (SCLC) is closely associated with smoking, but there has been little attention given to never-smokers. We retrospectively reviewed the clinical files of 271 consecutive SCLC patients who were newly diagnosed in Kinki-Chuo Chest Medical Center, Japan, from January 2004 through July 2010, and identified four cases (1.5%) who were never-smokers. They were all females, and their ages at the time of diagnosis were 55, 65, 66, and 77 years, respectively. We examined the clinical characteristics focused on family history of cancer (FHC) and environmental tobacco smoke (ETS). Two patients had primary cancers other than SCLS which were successfully treated before diagnosis of SCLC. All the cases had an FHC with exposure to ETS. One patient had both epidermal growth factor receptor and K-ras mutations. Our cases provided unique clinical characteristics and backgrounds in never-smokers with SCLC.
    Clinical Lung Cancer 05/2011; 13(1):75-9. DOI:10.1016/j.cllc.2011.04.001 · 3.10 Impact Factor
  • Cancer Research 01/2011; 70(8 Supplement):3733-3733. DOI:10.1158/1538-7445.AM10-3733 · 9.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small molecule inhibitors targeting epidermal growth factor receptor (EGFR) are known to be active against non-small cell lung cancer (NSCLC) although the pharmacodynamics of these agents on malignant pleural effusion (MPE) remains unclear. Here we describe a case of lung adenocarcinoma with massive MPE treated successfully by gefitinib and chest drainage. Using sequential MPE samples before and during gefitinib therapy, the morphological changes and apoptosis of cancer cells were analyzed. Apoptosis of cancer cells was detected as early as 4 hours on, but not before, gefitinib therapy, suggesting that the pharmacodynamic assessment of such molecular targeting agents might be feasible for MPE.
    Internal Medicine 01/2011; 50(7):745-8. DOI:10.2169/internalmedicine.50.4652 · 0.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To examine an association between environmental tobacco smoke (ETS) and activating epidermal growth factor receptor (EGFR) mutations in never-smokers with non-small cell lung cancer (NSCLC). A total of 126 never-smokers with NSCLC were prospectively included in this study. Detailed ETS information was obtained through a standardized questionnaire including exposure period, place, and duration. Cumulative dose of ETS (CETS) was evaluated as a sum of the number of the exposure years at home and/or workplace. EGFR and K-ras mutations were determined using real-time PCR amplification. A total of 124 patients (98.4%) had ETS exposure with median CETS of 50 years (range: 0-118). Activating EGFR mutations were detected in 62.7% of the 126 patients and K-ras in 2 of 114 patients. The incidence of activating EGFR mutations was significantly higher in females than in males (67.6% vs. 26.7%; P = 0.002), and increased in quintile groups separated on the basis of CETS (shortest group = 44.0%, longest = 84.6%; P = 0.0033). In the multivariate logistic regression model, including gender, CETS, age, and family history of cancer, both gender and CETS were significantly associated with an incidence of activating EGFR mutations; the odds ratio for the EGFR mutations were 5.13 [95% confidence interval, CI = 1.47-18.0; P = 0.0105] for females and 1.02 (95% CI = 1.00-1.04; P = 0.0193) for each 1-year increment in CETS. Females and increased ETS exposure are closely associated with EGFR mutations in never-smokers with NSCLC.
    Clinical Cancer Research 11/2010; 17(1):39-45. DOI:10.1158/1078-0432.CCR-10-1773 · 8.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It remains unclear whether response rate (RR) is related to survival benefit in phase III trials of advanced cancer treated with molecular targeted agents (MTA) in combination with standard therapies. We carried out a systematic search of PubMed for randomized phase III trials of four solid tumors examining the efficacy of MTA when added to a standard therapy. We examined whether there were any associations between RR increment obtained by the addition of targeted agents (DeltaRR) and survival benefit in phase III trials. We identified 26 phase III trials of MTA with a total of 21 156 patients and 29 experimental arms of MTA. Studies which showed significant survival benefit had higher DeltaRR compared with those which did not show significant benefit. In the receiver operating characteristic curve analysis, using a 7% gain as threshold value for DeltaRR allowed assessment of survival benefit with high sensitivity and specificity. There were also significant relationships between DeltaRR and hazard ratios for overall survival and progression-free survival in the linear regression analysis. RR increment obtained by the addition of MTA to a standard therapy may be useful to predict survival benefit in clinical phase III trials of advanced cancer.
    Annals of Oncology 08/2010; 21(8):1668-74. DOI:10.1093/annonc/mdp588 · 7.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There has been a growing interest in lung cancer in never-smokers. Utilizing a database from the National Hospital Study Group for Lung Cancer, information for never-smokers and ever-smokers with advanced non-small cell lung cancer was obtained from 1990 to 2005, including clinicopathologic characteristics, chemotherapy response, and survival data. Time of diagnosis was classified into two periods: 1990-1999 and 2000-2005. Multivariate analysis was performed using the Cox regression and logistic regression method, including gender, age, performance status, histology, stage, and period of diagnosis. There were 1499 never-smokers and 3455 ever-smokers with advanced stage IIIB and IV diseases who received cytotoxic chemotherapy. Never-smokers generally included more females, were younger, with better performance status and more adenocarcinoma diagnosed (p < 0.0001 for all). Smoking status was a significant prognostic factor (never-smoker versus ever-smoker; hazard ratio [HR] = 0.880, 95% confidence interval [CI]: 0.797-0.970; p = 0.0105). In separate multivariate analysis for never-smokers and ever-smokers, female gender and better performance status (p < 0.0001 for both) were both favorable prognostic factors. However, adenocarcinoma histology (versus squamous cell carcinoma; HR = 0.790, 95% CI: 0.630-0.990; p = 0.0403) and the period after 2000 (versus before 2000; HR = 0.846, 95% CI: 0.731-0.980; p = 0.0254) were significant only in the never-smokers, and younger age (HR = 1.007, 95% CI: 1.003-1.011; p = 0.0010) was significant only in the ever-smokers. In an exploratory analysis, different profiles were observed in predictive factors for chemotherapy response between the two groups. Never-smokers with non-small cell lung cancer lived longer than ever-smokers. Gender, histology, and time of diagnosis are important factors for prognosis in these patients.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2010; 5(7):1011-7. DOI:10.1097/JTO.0b013e3181dc213e · 5.28 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.3816/CLC.2010.n.035 · 3.10 Impact Factor

Publication Stats

5k Citations
789.11 Total Impact Points


  • 2013
    • Wakayama Medical University
      • Department of Internal Medicine
      Wakayama, Wakayama, Japan
  • 1997–2012
    • Kinki University
      • • Faculty of Medicine
      • • Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
    • Osaka Medical Center for Cancer and Cardiovascular Diseases
      Ōsaka, Ōsaka, Japan
  • 2011
    • Sakai City Hospital
      Sakai, Ōsaka, Japan
  • 2010
    • Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
      Ōsaka, Ōsaka, Japan
  • 2003–2009
    • Shizuoka Cancer Center
      Sizuoka, Shizuoka, Japan
  • 2008
    • Nagoya City University
      Nagoya, Aichi, Japan
  • 2007
    • Ibaraki Higashi Hospital
      Nakamurachō, Ibaraki, Japan
  • 2006
    • Aichi Cancer Center
      Nagoya, Aichi, Japan
  • 2000–2005
    • Rinku General Medical Center
      Ōsaka, Ōsaka, Japan
    • Toneyama National Hospital - Toyonaka
      Toyonaka, Ōsaka, Japan
    • Keio University
      • Department of Applied Chemistry
      Edo, Tōkyō, Japan
  • 1995–2002
    • Osaka City General Hospital
      Ōsaka, Ōsaka, Japan
  • 2001
    • Niigata Cancer Center Hospital
      Niahi-niigata, Niigata, Japan
  • 1998
    • Osaka Central Hospital
      • Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 1996
    • Kobe City Medical Center General Hospital
      Kōbe, Hyōgo, Japan
  • 1986–1996
    • NEC Corporation
      Edo, Tōkyō, Japan
  • 1992
    • Mitsubishi Electric Corporation
      Edo, Tōkyō, Japan