Introduction: S-1 is an oral fluoropyrimidine derivative, including three pharmacological compounds: tegafur, gimeracil and oteracil, in a molar ratio of 1: 0.4: 1.Areas covered: This review ...addresses the clinical evidence of S-1 in NSCLC in various clinical settings. Currently, S-1 for NSCLC is approved only in Japan. Prospective studies of S-1 as front-line and second-line chemotherapy with or without other agents and concurrent chemoradiotherapy are mainly reviewed. Only two Phase III clinical trials were published or presented for advanced NSCLC. S-1 and cisplatin is an active first-line chemotherapy regimen for advanced NSCLC and S-1 and carboplatin is noninferior to a carboplatin and paclitaexel regimen. The combination of S-1 and a platinum agent is active against NSCLC, regardless of tumor histology.Expert opinion: It is becoming possible to design effective regimens with S-1 against NSCLC in various clinical settings considering the ethnic differences in pharmacokinetics and a greater understanding of the underlying molecular pathways or biomarkers of NSCLC. Further Phase III studies with S-1 for both early and advanced NSCLC are warranted worldwide.
A randomized trial of vinorelbine plus gemcitabine followed by docetaxel (VGD) versus paclitaxel plus carboplatin (PC) in patients with advanced non-small-cell lung cancer showed no difference in ...overall survival (median survival time: 13.6 versus 14.1 months) between the two treatment groups. We report here the results of quality-of-life (QOL) study initiated in the mid-course of this randomized trial.
The patients themselves assessed the Functional Assessment of Cancer Therapy (FACT)-Lung (FACT-L), FACT-Taxane and the Functional Assessment of Chronic Illness Therapy - Spirituality (FACIT-Sp) QOL instruments at baseline and 6, 12 and 18 weeks after the treatment. The primary endpoint was a comparison of total QOL score for each assessment instrument between the two groups.
Sixty-eight patients from the trial (VGD, 34; PC, 34) who submitted baseline questionnaires and at least one questionnaire over the course of treatment were eligible. Longitudinal analysis showed a significant difference in slope of the FACT-Taxane score (p = 0.004) between treatment regimens over time, but no difference was found in FACT-L score (p = 0.311) and FACIT-Sp score (p = 0.466) between the two groups.
The significant difference in slope of FACT-Taxane score favored the VGD regimen. These data should be considered in treatment decision-making for patients with advanced non-small-cell lung cancer.
NCT00242983.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary To evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin (BLM), OK-432 (a pulverized product of heat-killed Streptococcus pyogenes ) or cisplatin ...plus etoposide (PE) for the management of malignant pleural effusion (MPE) in previously untreated non-small cell lung cancer. Eligible patients were randomized to the BLM arm: BLM 1 mg/kg (maximum 60 mg/body), the OK-432 arm: OK-432 0.2 Klinische Einheit units (KE)/kg (maximum 10 KE/body), or the PE arm: cisplatin (80 mg/m2 ) and etoposide (80 mg/m2 ). Pleural response was evaluated every 4 weeks according to the study-specific criteria. All responders received systemic chemotherapy consisting of PE every 3–4 weeks for two or more courses. Pleural progression-free survival (PPFS) was defined as the time from randomization to the first observation of pleural progression or death due to any cause. The primary endpoint was the 4-week PPFS rate. Of 105 patients enrolled, 102 were assessed for response. The 4-week PPFS rate for the BLM arm was 68.6%, 75.8% for the OK-432 arm, and 70.6% for PE arm. Median survival time (MST) for the BLM arm was 32.1 weeks, 48.1 weeks for the OK-432 arm, and 45.7 weeks for the PE arm. However, the outcomes did not differ significantly between groups. Toxicity was tolerable in all arms except for one treatment-related death due to interstitial pneumonia induced by BLM. We will select intrapleural treatment using OK-432 in the management of MPE in NSCLC for further investigation because it had the highest 4-week PPFS rate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Ectopic antidiuretic hormone syndrome is a medical emergency characterized by dilutional hyponatremia. Clinical effectiveness of the vasopressin V2 receptor antagonist mozavaptan was evaluated in 16 ...patients. In short-term (7-day) treatment with the drug, serum sodium concentration (mean ± standard deviation) significantly (P = 0.002) increased from 122.8 ± 6.7 to 133.3 ± 8.3 mEq/l, and symptoms due to hyponatremia were improved. On the basis of these results, mozavaptan (Physuline(®)) was approved as an orphan drug for the treatment of the syndrome in 2006 in Japan. During the 43 months following its launch, 100 patients have been treated with the drug; overall clinical effects of the drug were found similar to those of this clinical trial. Clinically, mozavaptan may allow hyponatremic patients to be treated by aggressive cancer chemotherapy with platinum-containing drugs. Moreover, the drug may free patients from strict fluid-intake restrictions and thereby improve their quality of life.
The dominant factors affecting porosity formation in laser powder bed fusion (PBF-LB/M) of an aluminum alloy were investigated through sparse modeling with the cross-sectional pore area ratio as the ...target variable and the process parameters of PBF-LB/M and the melting and solidification conditions of the alloy as the explanatory variables. A combination of a few explanatory variables that did not significantly increase the mean squared error for the relationship between the measured pore area ratios and the ratios estimated via the regression equations was found through lasso regression and backward elimination, which indicated that the energy density (one of the process parameters) and melt-pool depth (one of the melting conditions) were the dominant factors affecting the pore area ratio. The obtained regression coefficients for the energy density and melt-pool depth were negative and positive, respectively. In addition, the relationship between the energy density and melt-pool depth was curvilinear. These results suggest not only that the pore area ratio increases with the energy density and melt-pool depth but also that it decreases with an increase in the energy density or a decrease in the change rate of the pool depth under the range of the slow increase in the pool depth with an increase in the energy density.
Article Highlights
Dominant factors affecting porosity formation in AM of Al alloy were investigated through machine learning.
One of process parameters and one of melting conditions were dominant factors affecting pore area ratio.
Pore area ratio increases with the dominant factors, and then decreases with slow increase in one of the factors.
Background: The purpose of this study was to evaluate whether radiotherapy with carboplatin would result in longer survival than radiotherapy alone in elderly patients with unresectable stage III ...non-small cell lung cancer (NSCLC). Methods: Eligible patients were 71 years of age or older with unresectable stage III NSCLC. Patients were randomly assigned to the radiotherapy alone (RT) arm, irradiation with 60 Gy; or the chemoradiotherapy (CRT) arm, the same radiotherapy and additional concurrent use of carboplatin 30 mg/m2 per fraction up to the first 20 fractions. Results: This study was terminated early when 46 patients were registered from November 1999 to February 2001. Four patients (one in the RT arm, three in the CRT arm) were considered to have died due to treatment-related causes. The JCOG Radiotherapy Committee assessed these treatment-related deaths (TRDs) and the compliance with radiotherapy in this trial. They found that 60% of the cases corresponded to protocol deviation and 7% were protocol violation in dose constraint to the normal lung, two of whom died due to radiation pneumonitis. As to the effectiveness for the 46 patients enrolled, the median survival time was 428 days 95% confidence interval (CI) = 212–680 days in the RT arm versus 554 days (95% CI = 331 to not estimable) in the CRT arm. Conclusions: Due to the early termination of this study, the effectiveness of concurrent use of carboplatin remains unclear. We re-planned and started a study with an active quality control program which was developed by the JCOG Radiotherapy Committee.
Background Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC), and some common somatic mutations in EGFR have been ...examined for their ability to predict sensitivity to gefitinib or erlotinib. However, EGFR mutations at exon 20 have been reported to predict resistance to gefitinib therapy. Materials and methods We investigated the EGFR mutations and/or polymorphism statuses at kinase domain in 303 surgically treated non-small cell lung cancer (NSCLC) cases. One hundred ninety-four adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of kinase domains was analyzed by direct sequences. We have also investigated EGFR polymorphism status at exon 20 for 23 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. Results EGFR mutations at kinase domain were found in 75 of 303 lung cancer patients. During sequencing of EGFR tyrosine kinase domain in tumors, 86 EGFR polymorphism (G2607A) cases were identified at exon 20. G2067A polymorphism was significantly higher in nonadenocarcinomas (37.4%) than in adenocarcinoma (25.3%, P = 0.0415). The polymorphism status did not correlate with gender, smoking (never smoker versus smoker), and EGFR mutations. In 46 total gefitinib treated NSCLC patients, there was a tendency toward better prognosis in EGFR wild type (GG) patients than AG + AA patients. EGFR polymorphism in Japanese lung cancers seemed to be less frequent than Caucasian lung cancers. Conclusions EGFR-tyrosine kinase polymorphism might be associated with clinicopathological background of lung cancers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This Phase I/II trial was conducted to assess the efficacy and safety of PR-350, a novel hypoxic cell radiosensitizer, when administered with thoracic radiation therapy (RT) after induction ...chemotherapy (CT) for locally advanced non-small-cell lung cancer (NSCLC).
Two cycles of cisplatin (80 mg/m(2)) and paclitaxel (180 mg/m(2)), or carboplatin (AUC = 6) and paclitaxel (200 mg/m(2)) were given before RT of 60 Gy in 30 fractions. In the Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000 mg/m(2)) in combination with RT, and this number was increased in increments of 10 for successive groups to 30 doses.
In total, 37 patients were enrolled. In Phase I (n = 20), PR-350 could be administered 30 times with concurrent thoracic RT. Thus, in Phase II (n = 17), PR-350 was administered 30 times. The major toxicity was radiation pneumonitis, with Grade 3 or more pneumonitis noted in 6 patients (16%) including 2 with treatment-related deaths. However, no Grade 3 or more esophageal toxicity was noted, and only Grade 1 peripheral neuropathy was noted in 9 patients (24%). For all 37 patients, the median survival time (MST) and the 2-year survival rate were 15.9 months and 24%, respectively. For 18 patients receiving 21 to 30 doses of PR-350, the MST and 2-year survival rate were 20.9 months and 33%, respectively.
Thoracic RT combined with 30 daily administrations of PR-350 after induction CT was well tolerated and promising for locally advanced NSCLC.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
A new technique using a non-destructive inspection to predict the residual surface fatigue life of power transmission gears has recently attracted interest. This technique is advantageously applied ...to the preventive maintenance of a vehicle transmission, and also useful for developing power transmission gears with high reliability. However, the study of such a prediction has not yet been reported. The authors have carried out an experimental research concerning the subject using the X-ray diffraction method. The full-width at half-maximum (FWHM) was measured on the tooth surfaces of a pair of carburized gears by an X-ray diffractometer during a gear surface fatigue endurance test to investigate the progress of the surface fatigue. The results showed that the FWHM on the tooth surface fell rapidly at the beginning of the running. After that, under the condition of constant driving torque, the FWHM fell gradually in a higher Hertzian pressure area during the endurance running. On the other hand, the FWHM in a lower Hertzian pressure area was approximately stable. When the driving torque was changed during endurance running, the distinctive behavior of the FWHM was observed. Tooth surface damage occurred in a higher Hertzian pressure area when the normalized FWHM, newly developed by the authors, on the tooth surface decreased to a certain value. The authors propose a prediction method of the residual surface fatigue life of power transmission gears using the characteristic curve that expresses the relation between the normalized FWHM and the gear surface fatigue life.
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