A Phase I Trial of Weekly Nab-paclitaxel Plus Carboplatin With Thoracic Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: This study aimed to evaluate the safety and recommended dose of nab-paclitaxel in combination with carboplatin and thoracic radiotherapy for locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Nab-paclitaxel was administered weekly with escalating doses, combined with carboplatin area under the curve (AUC) 2 and concurrent standard thoracic radiotherapy. Escalating doses of nab-paclitaxel were as follows: level 0, 30 mg/m2; level 1, 35 mg/m2; level 2, 40 mg/m2; level 3, 45 mg/m2 Results: Twelve patients were enrolled and received the treatment according to the protocol; seven patients (58%) had squamous cell carcinoma and all cases had stage III disease. At level 1, none of the three patients experienced dose limiting toxicity (DLT). At level 2, one of the first three patients experienced a fatal DLT of bronchopulmonary hemorrhage. None of the three more additional patients experienced DLT. At level 3, two of the three patients experienced a DLT of grade 3 febrile neutropenia and grade 4 neutropenia, respectively. Consolidation chemotherapy was provided to 10 of 12 patients. Radiation pneumonitis developed in five of 12 patients (42%). Eight patients (66.7%) showed partial response, and four (33.3%) showed stable disease. For the above reasons, level 2 (40 mg/m2) was considered the recommended dose in this study. CONCLUSION: Concurrent chemoradiotherapy with weekly nab-paclitaxel (40 mg/m2) and carboplatin (AUC 2) is a feasible and well-tolerated regimen in patients with previously untreated locally advanced NSCLC. A phase II trial with this regimen is warranted.

Mustard gas exposure and mortality among retired workers at a poisonous gas factory in Japan: a 57-year follow-up cohort study.

OBJECTIVES: Mustard gas (MG) has been the most widely used chemical warfare agent in the past century. However, few but conflicting data exist on the effects of MG exposure on long-term mortality. We investigated MG-related mortality in retired workers at a poisonous gas factory. METHODS: We assessed mortality rates among 2392 male and 1226 female workers, whose vital status could be determined through 31 December 2009, at a poisonous gas factory operating from 1929 to 1945 in Okuno-jima, Japan. The analysis employed standardised mortality ratios (SMRs) calculated using national and prefectural references and a Cox proportional hazard regression model. Applying the Kaplan-Meier method, we compared cumulative death rates in the study cohort stratified by an 'Okuno-jima MG Index' which represented the product of HRs derived for job category and length of service. RESULTS: Among male workers, we found significant excesses in mortality from upper respiratory tract cancer (SMR 3.06), liver cancer (1.67), lung cancer (2.01) and chronic bronchitis/emphysema (4.84) compared with the national population, as well as stomach cancer (1.20) versus the Hiroshima Prefecture population. When stratified into 3 subgroups by the Okuno-jima MG Index, those with a higher Okuno-jima MG Index had significantly higher cumulative rates of death from respiratory cancer and chronic bronchitis/emphysema. CONCLUSIONS: MG exposure significantly increases the long-term risk of death from respiratory cancer and chronic bronchitis/emphysema. The Okuno-jima MG Index may be a useful indicator for estimating cumulative MG exposure.

[Clinical effects of budesonide/formoterol combination drug in elder patients with asthma compared with budesonide plus tulobuterol patch combination treatment].

BACKGROUND AND AIMS: Tulobuterol patch (Tulo) is often used for treatment of elder patient with asthma in Japan. However, there is no evidence either ICS plus Tulo or ICS/LABA combination is better for elder patient. METHODS: Elder patients with asthma (aged≥ 70, n=17) who had treated with budesonide (BUD) 400 µg/day plus Tulo 2 mg/day, were randomly assigned either to change control medication to budesonide/formoterol combination (BUD/FM) 320/9 µg/day or to keep BUD plus Tulo treatment for 12 weeks. RESULTS: At week 4 and week 12, the BUD/FM group showed significant increase in lung function (FEV1, %FEV1) and mini AQLQ score compared with the BUD plus Tulo group. The BUD/FM group also showed decrease in Tumor Necrosis Factor-alpha level in exhaled breath condensate at week 12. No adverse event was observed in both groups. CONCLUSION: In elder patients with asthma, treatment with BUD/FM does not have any clinical disadvantage and may provide better efficacy in lung function, QOL, and possibly anti-inflammation compared with BUD plus Tulo treatment.

A pilot study of the multiherb Kampo medicine bakumondoto for cough in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To evaluate the effect of bakumondoto, Kampo medicine, on cough in patients with chronic obstructive pulmonary disease (COPD). DESIGN: A 16-week, randomized, open-labeled, cross-over design. SETTING: Outpatient clinics at one university hospital and two general hospitals in Japan from May 2007 to March 2009. PARTICIPANTS: Twenty-four elderly patients (14 men and 9 women aged over 65) with COPD. INTERVENTION: Treatment with or without bakumondoto for 8 weeks in a cross-over design. MEASUREMENTS: The primary outcome measurements were the frequency and intensity of cough assessed by a visual analogue scale (VAS) and a daily cough diary. Secondary outcome measurements were quality of life (QOL) assessed using St. George's Respiratory Questionnaire (SGRQ) and lung functions measured using spirometry. RESULTS: Treatment with bakumondoto significantly improved cough severity during the first treatment period (week 0 vs. week 8, p=0.004) and showed a trend to decrease during the second treatment period (week 8 vs. week 16, p=0.129) assessed by the VAS. Neither QOL nor lung function was affected by the treatment with bakumondoto. CONCLUSION: Bakumondoto may be effective in suppressing cough in elderly patients with COPD. To further confirm the efficacy, a larger and placebo-controlled study with objective cough assessment is necessary.