Search

Purpose: To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis. Study design: Prospective clinical study. Methods: This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery. Results: The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee's grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations. Conclusion: BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the safety and the tolerability of combined cellular immunotherapy with low-dose cyclophosphamide (CPA) in patients with advanced solid tumors. This study targeted a novel tumor-associated antigen, ring finger protein 43 (RNF43). Eligible patients were resistant to standard therapy, HLA-A*24:02- or A*02:01-positive and exhibiting high RNF43 expression in their tumor cells. They were administered 300 mg/m2 CPA followed by autologous lymphocytes, preliminarily cultured with autologous RNF43 peptide-pulsed dendritic cells (DCs), RNF43 peptide-pulsed DCs and systemic low dose interleukin-2. The primary endpoint was safety whereas the secondary endpoint was immunological and clinical response to treatment. Ten patients, in total, were enrolled in this trial. Primarily, no adverse events greater than Grade 3 were observed. Six out of 10 patients showed stable disease (SD) on day 49, while 4 other patients showed progressive disease. In addition, one patient with SD exhibited a partial response after the second trial. The frequency of regulatory T cells (Tregs) in patients with SD significantly decreased after CPA administration. The ratio of interferon-γ-producing, tumor-reactive CD8+ T cells increased with time in patients with SD. We successfully showed that the combination of immune cell therapy and CPA was safe, might induce tumor-specific immune responses and clinical efficacy, and was accompanied by a decreased ratio of Tregs in patients with RNF43-positive advanced solid tumors. [ABSTRACT FROM AUTHOR]

Background Various polymorphisms have been detected in the UDP-glucuronosyltransferase 1 A ( UGT1A) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose ( MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism. Methods The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /− and *6 /−), were aged ≤75 years old, had a performance score of 0-1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36. Results Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2, but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment. Conclusions The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m(2) on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed. [ABSTRACT FROM AUTHOR]

Objectives: Concurrent chemoradiotherapy for regionally advanced stage III non-small cell lung cancer is the standard treatment method. However, the clinical implications of consolidation chemotherapy following chemoradiation have been unclear. Therefore, we conducted a phase II study of concurrent weekly carboplatin plus paclitaxel treatment in combination with radiotherapy followed by vinorelbine monotherapy. The primary endpoint was the 1-year survival rate. Patients and methods: Chemonaive PS 0–1 patients with stage IIIA/B NSCLC were enrolled. During the concurrent chemoradiation phase, patients were treated with weekly paclitaxel 40 mg/m 2 plus carboplatin AUC 2. The primary tumor and involved nodes received 60 Gy in 2-Gy fractions over 6 weeks. During the consolidation phase, vinorelbine 25 mg/m 2 on days 1 and 8 was repeated for three cycles. Results: A total of 40 eligible patients (72.5 % male; median age, 63 years; range 29–74 years) were analyzed for efficacy. Squamous cell carcinoma was the most common histology (47.5 %), and more patients had clinical stage IIIB (55 %) cancer. The average radiation dose was 56.5 Gy, and the average number of carboplatin plus paclitaxel cycles was 4.93. Seventeen patients proceeded to the consolidation chemotherapy phase, and 14 completed three cycles of vinorelbine monotherapy. The objective response rate was 75.0 %, including 1 patient who achieved a complete response. Progression-free survival and overall survival (OS) were 46 weeks [95 % confidence interval (CI) 31–64 weeks] and 110 weeks (95 % CI 90–184 weeks), respectively. The OS rate at 1 and 2 years was 85.0 % (95 % CI 69.6–93.0 %) and 53.9 % (95 % CI 37.1–68.0 %), respectively. Conclusion: Concurrent chemoradiation with weekly carboplatin and paclitaxel followed by vinorelbine consolidation is effective for stage III non-small cell lung cancer and shows a generally mild toxicity profile. [ABSTRACT FROM AUTHOR]

In spite of recent advances in chemotherapy, the treatment of pulmonary aspergilloma remains unsatisfactory. To evaluate the clinical efficacy and safety of combination therapy for pulmonary aspergilloma, we conducted a multi-institutional prospective study using micafungin (MCFG) and itraconazole (ITCZ). Adult patients who fulfilled the criteria for pulmonary aspergilloma were enrolled in this study. After patient consent had been obtained, intravenous MCFG 150 mg/day and an oral capsule of ITCZ 200 mg/day were administered for at least 1 month. The primary endpoint was the response assessed using an algorithm that incorporated the levels of improvement by evaluating clinical symptoms and signs, mycological and serological tests, and diagnostic imaging. A total of 17 patients were enrolled from three facilities. The response rate to the combination therapy was 58.8% (10/17). The long-term control in the group of patients who responded to treatment was better than that in the group of patients who did not respond. Adverse events occurred in 6 of the 17 patients (35.3%), but there were no severe adverse events. MCFG-ITCZ combination therapy appeared to be relatively safe and effective in patients with pulmonary aspergilloma. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab, a humanized antibody to vascular endothelial growth factor (VEGF), shows clinical activity against human cancer, with its addition to standard chemotherapy having been found to improve outcome in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). However, there have been no evidence-based studies to support the continued use of bevacizumab beyond disease progression in such patients treated with the drug in first-line therapy. We have now designed a randomized phase II trial to examine the clinical benefit and safety of continued bevacizumab treatment in patients with advanced nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet.Methods/Design: WJOG 5910L was designed as a multicenter, open-label, randomized, phase II trial by the West Japan Oncology Group of docetaxel (arm A) versus docetaxel plus bevacizumab (arm B) in patients with recurrent or metatstatic nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet. Patients in arm A will receive docetaxel at 60 mg/m2 and those in arm B will received ocetaxel at 60 mg/m2 plus bevacizumab at 15 mg/kg, with each drug administered on day 1 every 21 days until progression or unacceptable toxicity. The primary endpoint of the study is progression-free survival, with secondary endpoints including response rate, overall survival, and safety, for patients treated in either arm.Trial registration: UMIN (University Hospital Medical Information Network in Japan) 000004715 [ABSTRACT FROM AUTHOR]

Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m2) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis. [ABSTRACT FROM AUTHOR]

Lessons Learned: Updated survival data for a phase I/II study of carboplatin plus nab‐paclitaxel and concurrent radiotherapy were collected.In the group of 58 patients who were enrolled at 14 institutions in Japan, the median overall survival was not reached and the 2‐year overall survival rate was 66.1% (95% confidence interval, 52.1%–76.8%).Results reveal encouraging feasibility and activity for this regimen. Background: We report the updated survival data for a phase I/II study of carboplatin plus nab‐paclitaxel (nab‐P/C) and concurrent radiotherapy (CRT) in patients with locally advanced non‐small cell lung cancer (NSCLC). Methods: Individuals between 20 and 74 years of age with unresectable NSCLC of stage IIIA or IIIB and a performance status of 0 or 1 were eligible for the study. Patients received weekly nab‐paclitaxel at 50 mg/m2 for 6 weeks together with weekly carboplatin at an area under the curve (AUC) of 2 mg/ml/min and concurrent radiotherapy with 60 Gy in 30 fractions. This concurrent phase was followed by a consolidation phase consisting of two 3‐week cycles of nab‐paclitaxel (100 mg/m2 on days 1, 8, and 15) plus carboplatin (AUC of 6 on day 1). After the treatment, patients were observed off therapy. The primary endpoint of the phase II part of the study was progression‐free survival (PFS). Results: Between October 2014 and November 2016, 58 patients were enrolled at 14 institutions in Japan, with 56 of these individuals being evaluable for treatment efficacy and safety. At the median follow‐up time of 26.0 months (range, 4.0–49.6 months), the median overall survival (OS) was not reached (95% confidence interval [CI], 25.3 months to not reached) and the 2‐year OS rate was 66.1% (95% CI, 52.1%–76.8%). The median PFS was 11.8 months (95% CI, 8.2–21.0 months), and the 2‐year PFS rate was 35.9% (95% CI, 23.1%–48.9%). Subgroup analysis according to tumor histology or patient age revealed no differences in median PFS or OS. Long‐term follow‐up of toxicities did not identify new safety signals, and no treatment‐related deaths occurred during the study period. Conclusion: Concurrent chemoradiation with nab‐P/C was safe and provided a long‐term survival benefit for patients with locally advanced NSCLC. [ABSTRACT FROM AUTHOR]

Lessons Learned: The biweekly GEM plus CBDCA dose and schedule showed satisfactory efficacy with mild toxicities in elderly patients with advanced NSCLC.The biweekly GEM plus CBDCA regimen could be considered an alternative to the 3‐week regimen in NSCLC. Background: The gemcitabine (GEM)‐carboplatin (CBDCA) combination is widely used for non‐small cell lung cancer (NSCLC) and has some efficacy in elderly patients; however, a high incidence of thrombocytopenia is observed, and the optimal dosage and administration schedules are unknown. This multicenter phase II trial evaluated the efficacy and tolerability of GEM‐CBDCA for elderly patients with chemotherapy‐naive NSCLC. Methods: Patients with chemotherapy‐naive performance status 0–1 and with stage IIIB/IV NSCLC were administered chemotherapy biweekly (GEM 1,000 mg/m2 with CBDCA area under the blood concentration‐time curve (AUC) 3 on days 1 and 15 every 4 weeks). The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression‐free survival (PFS), overall survival (OS), and safety. Results: Forty‐eight patients were enrolled. Median age was 76 years (range, 70–83); 35 patients were men (73%), and 27 patients had adenocarcinoma (56%). The ORR was 29.2% (95% confidence interval [CI], 17.0–44.1). The median PFS, median OS, and 1‐year survival was 5.9 months (95% CI, 4.1–6.6), 13.3 months (95% CI, 8.3–23.5), and 58%, respectively. Grade ≥3 hematological toxicities included neutropenia (29.2%), thrombocytopenia (4.2%), and anemia (20.8%). The incidence of grade ≥3 nonhematological toxicities was <5%. Conclusion: This GEM‐CBDCA combination administered biweekly showed satisfactory efficacy with mild toxicities in elderly patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Objectives We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non–small cell lung cancer (NSCLC). Methods Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100 mg/m 2 ) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR). Results Forty-one patients were enrolled between September 2013 and April 2015. The ORR was 31.7% (90% confidence interval, 19.3%–44.1%), which met the primary objective of the study. Median progression-free survival was 4.9 months (95% confidence interval, 2.4–7.4 months) and median overall survival was 13.0 (95% confidence interval, 8.0–18.0 months) months. The median number of treatment cycles was four (range, 1–17) over the entire study period, and the median dose intensity was 89.1 mg/m 2 per week. Hematologic toxicities of grade 3 or 4 included neutropenia (19.5%) and leukopenia (17.1%), with no cases of febrile neutropenia being observed. Individual nonhematologic toxicities of grade 3 or higher occurred with a frequency of <5%. Conclusion Weekly nab-paclitaxel was associated with acceptable toxicity and a favorable ORR in previously treated patients with advanced NSCLC. Our results justify the undertaking of a phase III trial comparing nab-paclitaxel with docetaxel in this patient population. [ABSTRACT FROM AUTHOR]

We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4 days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4 weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies. [ABSTRACT FROM AUTHOR]

We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress plays a critical role in the development of pulmonary fibrosis. However, the effects of treatment with anti-oxidant agents against pulmonary fibrosis have not yet been thoroughly investigated. In this study, the effect of MCI-186, a novel free radical scavenger, on bleomycin-induced pulmonary fibrosis was investigated. Bleomycin (0.05units/mouse) was administered intratracheally into C57Bl/6 mice. MCI-186 was given to bleomycin-treated mice intraperitoneally from (i) day −3 to day 7, or from (ii) day 10 to day 28 after bleomycin administration in successive days. At 28 days after bleomycin administration, pulmonary fibrosis was then assessed by lung histology and hydroxyproline. MCI-186 inhibited H2O2-induced DNA damage in bronchial epithelium in vitro. MCI-186 decreased the lipid peroxide content, a marker for DNA damage, in the lung and reduced 8-OHdG positive cells in the lung in vivo. During the early period (day −3 to day 7) administration, MCI-186 partially attenuated bleomycin-induced pulmonary fibrosis. However, during the late period (day 10 to day 28) MCI-186 exacerbated pulmonary fibrosis, based on the histology and hydroxyproline content. In this condition, MCI-186 in the late period decreased the number of apoptosis cells induced by bleomycin, and therefore it might contribute to the deterioration of pulmonary fibrosis. These data indicate that MCI-186, radical scavenger, has a biphasic effect on bleomycin-induced pulmonary fibrosis in mice. Careful attention should be paid before clinical application of new remedies for pulmonary fibrosis. [Copyright &y& Elsevier]