Probably the Mycobacterium avium Complex around the Staple Line Exacerbated after Radiation Therapy.

The space around the staple line after lung surgery is at high risk of nontuberculosis Mycobacterium pulmonary disease (NTM-PD). Solitary nodules of NTM-PD around the staple line are difficult to distinguish from lung cancer. There is no clear identification from laboratory data and radiologic findings without histological examination. In the present case, we misdiagnosed the pulmonary granulomas with Mycobacterium avium complex pulmonary disease (MAC-PD) as a recurrence of lung cancer. We conducted radiation therapy. The pulmonary granulomas with MAC-PD were exacerbated by irradiation. The effects of radiation therapy for MAC-PD are unknown. When radiation therapy is performed for the patient coexistence with MAC-PD, we should pay attention to exacerbation of MAC-PD.

Phase II Study of Weekly Nanoparticle Albumin-Bound Paclitaxel as Second- or Third-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) are poor due to limited treatment options. OBJECTIVE: We conducted a multicenter, single-arm phase II study to prospectively assess the efficacy and safety of weekly nab-PTX in patients with advanced NSCLC with failed cytotoxic chemotherapy. METHODS: Patients with advanced NSCLC having adequate organ functions with a performance status of 0-1 were enrolled. A 100 mg/m2 dose of nab-paclitaxel was administered on days 1, 8, and 15 of a 28-day cycle. Primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), toxicity profile, progression-free survival (PFS), and overall survival (OS). RESULTS: Between September 2013 and May 2016, 35 patients were enrolled. The ORR was 31.4%, and the DCR was 74.3%. The median PFS was 3.6 months, and the median OS was 11.4 months. The most common grade 3 or 4 toxicities included neutropenia (54.3%), leukopenia (42.9%), and anemia (11.4%). Two patients discontinued chemotherapy due to pneumonitis. CONCLUSIONS: Nab-PTX may be a later-line chemotherapeutic option for previously treated advanced NSCLC.

Administration of docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte colony-stimulating factor for pretreated non-small cell lung cancer: a phase II study.

PURPOSE: Although docetaxel plus ramucirumab has shown superior treatment efficacy over docetaxel monotherapy for patients with non-small cell lung cancer (NSCLC), the high rate of febrile neutropenia (FN) presents a clinical problem. This study aimed to validate the primary prophylactic use of pegfilgrastim with docetaxel and ramucirumab treatment in Japanese patients with NSCLC. METHODS: Patients with NSCLC with progression after at least one round of chemotherapy were enrolled and administered docetaxel (60 mg/m2) plus ramucirumab (10 mg/kg) intravenously on day 1, followed by pegylated-granulocyte colony-stimulating factor (3.6 mg) on day 2 of a 21-day treatment cycle. The primary study endpoint was the percentage of patients who developed FN. Secondary endpoints included overall survival, progression-free survival, overall response rate, and safety. RESULTS: Overall, 20 patients (15 men and 5 women) were enrolled, of whom one developed FN, resulting in an overall FN rate of 5%. The response and disease control rates were 40% and 85%, respectively. The median progression-free survival was 6.6 (95% confidence interval [CI], 0.5-NR) months. The median overall survival was 18.4 (95% CI, 2.2-11.0) months. Six patients aged over 75 years were included in this study, and although most adverse events were durable, ramucirumab-associated adverse events occurred more frequently in these patients. CONCLUSIONS: We observed a 5% FN rate using primary prophylactic pegylated-granulocyte colony-stimulating factor with docetaxel plus ramucirumab in Japanese patients with NSCLC. While most adverse events were durable, elderly patients should be closely monitored.

Predictors of Discontinuance of Oral Feeding in Patients With Advanced Alzheimer Dementia and Aspiration Pneumonia in Japan: A Single-center, Retrospective Observational Study.

BACKGROUND: Difficulty with oral feeding, the most commonly observed complication of Alzheimer disease (AD) in its final stages, occurs in 86% of AD patients and may prevent achievement of oral feeding after aspiration pneumonia. However, no reliable indicators of discontinuance of oral feeding have yet been identified. We therefore aimed to identify predictors of discontinuance of oral feeding in postaspiration pneumonia patients with AD. MATERIALS AND METHODS: Relevant clinical and laboratory data of 60 patients with AD admitted to our hospital in Japan for aspiration pneumonia were retrospectively compared between oral feeding and discontinuance groups. RESULTS: The study groups differed in interval since diagnosis of AD, CURB-65 score, pneumonia severity index score, and proportion of patients who died (higher in the discontinuance group) and body mass index (BMI), Mini Mental State Examination (MMSE) score, and functional independence measure score (lower in the discontinuance group). According to multivariate logistic regression analysis of all identified independent variables, only CURB-65 and MMSE scores and BMI are significant predictors of discontinuance of oral feeding after aspiration pneumonia in patients with advanced AD. CONCLUSIONS: In patients with advanced AD, discontinuance of oral feeding after aspiration pneumonia may be predicted by CURB-65 and MMSE scores and BMI.

A phase II study of afatinib treatment for elderly patients with previously untreated advanced non-small-cell lung cancer harboring EGFR mutations.

OBJECTIVE: The efficacy and safety of afatinib in elderly patients with EGFR-mutated non-small-cell lung cancer (NSCLC) have not been evaluated. This study aimed to assess the efficacy and safety of afatinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. MATERIALS AND METHODS: We prospectively assessed the clinical effects of afatinib as a first-line treatment for elderly (age ≥70 years) NSCLC patients with EGFR mutations (exon 19 deletion or exon 21 L858R mutation). All patients were initially administered afatinib (30 mg/day). RESULTS: Between May 2014 and August 2017, 40 patients (13 men, 27 women) with adenocarcinoma were included in our analysis. The median age was 77 years (range, 70-85 years). The dose was reduced in 19 patients. The objective overall response and disease control rates were 72.5% and 100%, respectively, and the median progression-free survival and overall survival were 12.9 months and not reached, respectively. Common adverse events (AEs) included diarrhea, rash/acne, and anemia. Major grade 3 or higher toxicities included diarrhea (12.5%), mucositis (7.5%), and pneumonitis (7.5%). Afatinib treatment was discontinued in 8 patients owing to AEs of elevated amylase (n = 1), liver dysfunction (n = 1), rash/acne (n = 1), nail change (n = 1), anorexia (n = 2), pneumonitis (n = 2), and diarrhea (n = 2). Two patients died due to treatment-related pneumonitis. CONCLUSIONS: This is the first study that verified the efficacy and feasibility of first-line chemotherapy with afatinib at 30 mg/day in elderly patients with advanced NSCLC harboring sensitive EGFR mutations. First-line afatinib of 30 mg/day could be a treatment option in this patient population.

Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer.

PURPOSE: In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients. METHODS: The medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed. The median BSA and BW were used as cutoff values to evaluate their impact on gefitinib efficacy. BMI was categorized as underweight (<18.5 kg/m2), normal (18.5-25 kg/m2), and overweight (≥25 kg/m2). RESULTS: The median BSA and BW were 1.48 m2 and 53 kg, respectively. The overall response rate, progression-free survival (PFS), and overall survival (OS) were 65.2%, 12.2, and 24.2 months, respectively. There were no significant differences in clinical outcomes according to BSA, BW, or BMI alone. Subgroup analysis based on the mutation type and BSA revealed no significant differences in PFS between the groups; however, the median OS in those with exon 19 deletion combined with low BSA was significantly favorable compared with the other groups. CONCLUSIONS: Gefitinib efficacy in patients with NSCLC harboring sensitive EGFR mutations did not differ according to BSA, BW, and BMI. However, OS was superior in patients with both the exon 19 deletion and low BSA.

Phase I dose escalation study of amrubicin plus paclitaxel in previously treated advanced non-small cell lung cancer.

BACKGROUND: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the safety profile of amrubicin (AMR) plus paclitaxel (PTX) combination regimen for patients with previously treated non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: PTX was administered at a fixed dose of 150 mg/m(2)/day on day 1 and AMR was intravenously administered at a starting dose of 25 mg/m(2)/day on days 1-3, and this was repeated every 4 weeks. Doses of each drug were planned as follows-level 0, 20/150; level 1, 25/150; level 2, 30/150; level 3, 30/180 AMR mg/m(2) per day/PTX mg/m(2) per day. RESULTS: Twelve patients were enrolled in this study. The dose-limiting toxicity (DLT) of the regimen was assessed during the first cycle. At level 1, all three patients developed a DLT due to grade 4 neutropenia lasting >4 days, grade 4 thrombocytopenia and grade 3 febrile neutropenia. Therefore, level 1 was considered the MTD and level 0 was selected as the RD. Objective responses were seen in two patients (response rate 16.7 %). Overall disease control rate was 91.7 %. CONCLUSIONS: The combination of AMR and PTX is a feasible and well-tolerated regimen for the treatment of patients with previously treated advanced NSCLC. Although our study included a small number of patients, encouraging disease control and progression-free survival were achieved at the recommended doses. Further clinical trials are warranted.

Hydroxyurea-induced Pneumonitis in a Patient with Chronic Myelomonocytic Leukemia: An Autopsy Case.

We describe the case of an 85-year-old man diagnosed with chronic myelomonocytic leukemia whose disease was treated with hydroxyurea for 3 months. He developed respiratory symptoms that were extensively investigated. Despite the intensive treatment, he died of respiratory failure eleven days later. An autopsy revealed diffuse interstitial inflammation of both lungs consistent with drug-induced inflammation. A drug lymphocyte stimulation test was positive for hydroxyurea. Taken together these findings demonstrated that severe interstitial pneumonitis was induced by this drug. Physicians using hydroxyurea must be aware of its potentially life-threatening pulmonary toxicity.

First-line gefitinib treatment in elderly patients (aged ≥75 years) with non-small cell lung cancer harboring EGFR mutations.

PURPOSE: The efficacy of gefitinib [an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor] in elderly patients with non-small cell lung cancer (NSCLC) and EGFR mutation has not been elucidated. Therefore, the objective of this study was to investigate the efficacy and feasibility of gefitinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. METHODS: We retrospectively evaluated the clinical effects of gefitinib as a first-line treatment for elderly (≥75 years) NSCLC patients with EGFR mutations (exon 19 deletion or exon 21 L858R mutation). All patients were initially treated with gefitinib (250 mg/day) at seven institutions. RESULTS: Between January 2006 and December 2012, 62 patients (17 men, 45 women) with a median age of 80 years (range, 75-89 years) were included in our analysis. The overall response and disease control rates were 61.2 and 83.8 %, respectively, and the median progression-free survival and overall survival were 13.2 and 19.0 months, respectively. Common adverse events included rash, diarrhea, and liver dysfunction. Major grade 3 or 4 toxicities included skin rash (3.2 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (21.0 %). Gefitinib treatment was discontinued owing to adverse events of liver dysfunction in 3 patients, drug-induced pneumonitis in 2, and diarrhea in 1. CONCLUSION: First-line gefitinib could be a preferable standard treatment in elderly patients with advanced NSCLC harboring sensitive EGFR mutations.

[A case of clinically diagnosed eosinophilic bronchiolitis].

A 71-year-old man was referred to our hospital because of an intractable productive cough. Although he was treated for bronchial asthma, the symptom did not improve. Furthermore, since he developed progressive dyspnea and hypoxemia, he was admitted to our hospital. Marked eosinophilia in a blood test and sputum, poorly defined centrilobular nodules throughout the bilateral lung fields in a chest CT scan, and mixed ventilatory impairment in a spirometric test were revealed. Thoracoscopic lung biopsy and bronchoalveolar lavage were not conducted because of progressive respiratory failure. Therefore, we clinically diagnosed eosinophilic bronchiolitis, and immediately administered oral prednisolone (30 mg daily). His symptoms and examination findings rapidly improved. This case suggests that eosinophilic bronchiolitis should be taken into consideration for differential diagnoses of eosinophilic lung disease and obstructive lung disease, and marked eosinophilia in sputum may be one of the useful tools for diagnosis of this disease when invasive examinations are inadequate.