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Small-cell lung cancer (SCLC) is a highly malignant tumor, and no standard third-line therapy has been established. The present study retrospectively analyzed the efficacy and safety of platinum-based regimens in patients with third-line SCLC who received third-line chemotherapy. The association of regimen type with overall survival (OS) or time to treatment failure (TTF) was evaluated using the Cox hazard proportional method, including well-known covariates affecting the prognosis of SCLC. TTF and OS analyses were conducted using the Kaplan-Meier method. The data cutoff date was June 30, 2020. As a result, from January 2015 to August 2019, 111 patients were diagnosed with SCLC, and 37 received third-line chemotherapy. Subsequently, 15 patients received a platinum-doublet regimen, and 22 patients received a single-agent regimen. Only the type of regimen was significantly associated with TTF in univariate analysis (odds ratio, 0.44; 95% confidence interval, 0.20-0.95; P=0.03). There were no significant factors associated with OS. The median TTF of patients receiving a platinum-doublet regimen and those receiving a single-agent regimen were 3.9 and 2.3 months, respectively (P=0.03). The overall response rates of the platinum-doublet and single-agent regimens were 20.0 and 4.5%, respectively. Similarly, the disease control rates were 73.3 and 36.4% for platinum-doublet and single-agent regimens, respectively. There was a tendency for adverse events (AEs) with any grade to occur more often in platinum-based regimens compared with in single-agent regimens. Severe AEs of grade 3 or higher were observed more often in the platinum-based regimen, especially in myelosuppression. In conclusion, the present study demonstrated the feasibility and safety of platinum-doublet regimens in patients with SCLC in a third-line setting (Registration no. 2020-048. Date of registration, June 5, 2020).

Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for mutant non-small cell lung cancer (NSCLC), was approved in Japan in 2014. This study evaluated clinical outcomes of afatinib in real-world practice. Medical records of patients who received afatinib for advanced EGFR-mutant NSCLC were retrospectively reviewed. In total, 128 patients were analyzed. Seventy-six patients received afatinib as the first-line setting and 52 as the re-challenge setting (i.e., after failure of prior first-generation TKI). There was no difference in patient characteristics, such as age, sex, and PS, between the first-line and the re-challenge settings. In the first-line setting, the median progression-free survival (PFS) was 17.8 months (95% confidence interval [CI] 13.7-21.5 months). The overall survival (OS) was 39.5 months (95% CI 34.4- not reached). The response rate (RR) was 64.4%. Subset analysis indicated that patients with dose reduction showed longer PFS than those without dose reduction (18.5 months versus 7.9 months) (P = 0.016). In the re-challenge setting, the median PFS was 8.0 months (95% CI 4.9-9.5 months). The RR was 25%. Most common adverse events leading to dose modification or treatment discontinuation included diarrhea, paronychia, and oral mucositis in both settings. Interstitial lung disease occurred in 5.4% (7/128). In the real-world practice in Japan, afatinib showed comparable or better efficacy compared with that shown in previous clinical trials in both the first-line and the re-challenge settings.

Objective To clarify the clinical significance of vascular endothelial growth factor (VEGF) in Japanese patients with small cell lung cancer (SCLC).Materials and Methods We measured serum VEGF levels using an enzyme-linked immunosorbent assay in 45 patients with SCLC before treatment and in 38 patients with benign pulmonary disease and in 32 healthy subjects (71 non-malignant subjects). VEGF immunostaining was performed in tissue biopsies obtained from 23 SCLC patients during bronchoscopic examination.Results Median serum VEGF level was 332 pg/ml in patients with SCLC and 160 pg/ml in non-malignant subjects, respectively. The 95% cut-off level to exclude non-malignant subjects was 500 pg/ml. An elevated VEGF level (>500 pg/ml) was found more frequently in patients with extensive disease of SCLC than in those with the limited disease (p

The purpose of this study was to determine the safety and efficacy of nedaplatin and paclitaxel when given concurrently with radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC).Nedaplatin was administered at a fixed dose of 20 mg/m(2), and paclitaxel was administered at a starting dose of 30 mg/m(2) with an incremental increase of 5 mg/m(2) until dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered once a week for 6 weeks. The RT was given at a single daily dose of 2 Gy for 5 days per week. The pharmacokinetics of nedaplatin and paclitaxel were investigated.Overall, 20 patients were recruited and assigned to three different treatment groups: group 1 (paclitaxel 30 mg/m(2)), group 2 (paclitaxel 35 mg/m(2)) and group 3 (paclitaxel 40 mg/m(2)). Pulmonary toxicity was the main toxicity which occurred in 16 of 20 patients. In group 3, grades 3 and 4 pulmonary toxicity occurred in two of six patients and grade 3 esophagitis in one patient. The maximum tolerated dose of paclitaxel in this study was 40 mg/m(2) and the recommended dose of paclitaxel was therefore 35 mg/m(2). Four complete and 11 partial responses were observed, resulting in a 75% overall response rate. The area under the concentration-time curve of paclitaxel in group 3 was significantly higher than that in group 1.Nedaplatin 20 mg/m(2) and paclitaxel 35 mg/m(2) could be safely administered for NSCLC with concurrent thoracic RT, and this regimen was effective. The most important DLT was pulmonary toxicity.

Objectives: We conducted a phase II study to evaluate the combination of bi-weekly docetaxel and S-1, a novel oral fluorouracil derivative, for patients with previously treated non-small cell lung cancer. Methods: Patients received S-1 on days 1-14 and docetaxel on days 1 and 15 of each 28-day cycle. The primary endpoint was overall response rate (ORR). Results: We enrolled 35 pts from 7 institutions (Feb. 2007-Sep. 2008). Patient characteristics: male/female, 23/12; median age, 64 years; and PS, 0/1 (17/18). The ORR was 26% (95% confidence interval, 11-40). The median progression-free survival was 4.1 months and the median overall survival was 16.3 months. Hematologic grade 3/4 toxicity included neutropenia (31%) and anemia (11%). Major non-hematologic grade 3 toxicity included diarrhea (17%). Conclusions: The combination of S-1 and bi-weekly docetaxel is an active regimen with a tolerable toxicity for previously treated NSCLC. Further evaluation of this regimen is warranted.

Summary Background Diagnosing tuberculous pleural effusion (pTB) is often difficult because the culturing of tubercle bacilli results in a negative test in the majority of cases. Serological tests for the detection of antibodies to tuberculous glycolipid (TBGL) and lipoarabinomannan (LAM) have been introduced for the diagnosis of pulmonary tuberculosis. We examined the levels of these antibodies, adenosine deaminase (ADA) and interferon- γ (IFN- γ ) in the pleural effusion and compared their diagnostic values in pTB. Methods We studied 65 patients with pleural effusion. Of those, 19 patients were diagnosed as having pTB according to our broad case definition. The etiologies in the other 46 patients were malignant effusion, transdative effusion and miscellaneous diseases. Determiner TBGL antibody ® (D-TBGL-Ab) and MycoDot ® were used for the detection of anti-LAM and anti-TBGL antibodies, respectively, in the pleural effusion. Results The sensitivity of ADA was 78.9% (15/19) and the specificity 97.8% (45/46). The sensitivity of IFN- γ was 84.2% (16/19) and the specificity 93.5% (43/46). The sensitivities of D-TBGL-Ab and MycoDot ® were both 52.6% (10/19) and their specificities were 95.7% (44/46) and 97.8% (45/46), respectively. When DTBGL-Ab (cutoff point: 2.0U/ml) and ADA activity (cutoff point: 57IU/l) were combined, the sensitivity was 94.7% (18/19) and the specificity 93.5% (43/46). Conclusions In the diagnosis of pTB, D-TBGL-Ab and MycoDot ® each have low sensitivity but high specificity. When D-TBGL-Ab is used in combination with ADA, the sensitivity and specificity are both >90%. We conclude that D-TBGL-Ab and ADA in combination are useful in the diagnosis of pTB.

Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated good response in NSCLC harboring EGFR gene mutation. However, survival benefit from erlotinib was observed also in NSCLC patients with wild-type (wt) EGFR gene in subsets of several phase III trials. Additionally, smoking status could be a predictive factor of erlotinib efficacy. This study aimed to evaluate the efficacy of erlotinib in Japanese NSCLC patients with wt-EGFR and find a biomarker that predicts the efficacy of erlotinib other than EGFR gene mutation. Methods The primary end point was an objective response rate. Secondary end points included disease control rate, overall survival, safety and a biomarker finding. Advanced NSCLC patients without EGFR gene mutation who had received one to three prior chemotherapy regimens and who had never smoked or light smoked (smoking index: Results Forty-seven patients were enrolled between March 2010 and November 2011. One patient was excluded for evaluation because having mutation of EGFR. Efficacy and safety were evaluated among 46 patients. Best responses were: PR 7 (15.2%), SD 12 (26.1%), PD 26 (46.4%), NE 1 (2.2%). Response rate and disease control rate were 15.2% (95% CI: 4.9–25.5%) and 41.3 % (95% CI 27.1–55.5%), respectively. Grade 3 or 4 adverse events were anorexia (4), skin rash (2), neutropenia (1), leukopenia (1), anemia (2), elevation of AST/ALT (1), rectal ulcer (1) and cerebral infarction (1).Two patients suffered grade 3 interstitial lung disease. Conclusion This is the first report to evaluate Erlotinib efficacy in selected NSCLC who do not possess EGFR gene mutation. Erlotinib showed significant anti-tumor activity in pretreated never or light smoked Japanese NSCLC patients without EGFR gene mutation.