Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403).

The purpose of this study was to evaluate the efficacy of gefitinib and the feasibility of screening for epidermal growth factor receptor (EGFR) mutations among select patients with advanced non-small cell lung cancer (NSCLC). Stage IIIB/IV NSCLC, chemotherapy-naive patients or patients with recurrences after up to two prior chemotherapy regimens were eligible. Direct sequencing using DNA from tumour specimens was performed by a central laboratory to detect EGFR mutations. Patients harbouring EGFR mutations received gefitinib. The primary study objective was response; the secondary objectives were toxicity, overall survival (OS), progression-free survival (PFS), 1-year survival (1Y-S) and the disease control rate (DCR). Between March 2005 and January 2006, 118 patients were recruited from 15 institutions and were screened for EGFR mutations, which were detected in 32 patients--28 of whom were enrolled in the present study. The overall response rate was 75%, the DCR was 96% and the median PFS was 11.5 months. The median OS has not yet been reached, and the 1Y-S was 79%. Thus, gefitinib chemotherapy in patients with advanced NSCLC harbouring EGFR mutations was highly effective. This trial documents the feasibility of performing a multicentre phase II study using a central typing laboratory, demonstrating the benefit to patients of selecting gefitinib treatment based on their EGFR mutation status.

Inhibitory effects of resin composite containing bactericide-immobilized filler on plaque accumulation.

OBJECTIVE: Previously, we have reported that incorporation of the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) was effective in immobilizing bactericide in the resin matrix, and an antibacterial composite without release of the agent could be achieved. In this study, an attempt was made to increase the density of bactericide immobilized in composite, and the inhibitory effects of this modified antibacterial composite on plaque accumulation were determined, focusing on the reliability of the effects and the mechanisms to affect the plaque formation. METHODS: An experimental composite containing immobilized bactericide at 2.83% was prepared by the incorporation of MDPB into a prepolymerized resin filler of control composite, and elution of antibacterial components and inhibition of in vitro plaque accumulation by Streptococcus mutans were determined. The inhibitory effects of the experimental composite on the attachment, glucan synthesis and growth of S. mutans on the surface were also examined in addition to the comparison of surface roughness and hydrophobicity with controls. The results were analyzed using the Student's t-test. RESULTS: The experimental composite had reproducible inhibitory effects against plaque accumulation compared with control (p<0.05), although it showed no elution of unpolymerized MDPB. The plaque-inhibitory effect of the experimental composite was found to depend upon the ability to inhibit the attachment, glucan synthesis, and growth of bacteria on its surface as no significant differences in the surface characteristics were obtained between control and experimental composites (p>0.05). SIGNIFICANCE: It was indicated that the experimental composite containing bactericide-immobilized filler has the possibility to be used clinically with an effective anti-plaque property.

Bactericidal effect of dentin primer containing antibacterial monomer methacryloyloxydodecylpyridinium bromide (MDPB) against bacteria in human carious dentin.

The aim of this study was to investigate the bactericidal effect of a dentin primer incorporating the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) against bacteria in human dentinal carious lesions. To evaluate the antibacterial activity of MDPB against anaerobes, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against obligate anaerobes and facultative anaerobic strains of lactobacilli were determined. Bacteria were recovered from carious dentin samples obtained from the teeth of patients, and the bactericidal activities of the experimental primer containing 5% MDPB and three commercially available primers were compared by counting the number of viable cells after contact with diluted solutions of each primer for 30 s. MDPB showed strong antibacterial activity against anaerobes, the MIC and MBC values ranging from 3.9 to 31.3 micrograms/ mL-1 and 15.6-125 micrograms/ mL-1, respectively. Experimental primer containing MDPB was the most bactericidal among the materials tested (ANOVA, Fisher's PLSD test, P < 0.05) and was able to kill the bacteria completely even when diluted 40 times, while the three commercial products exhibited little activity at 40 times dilution. These results indicate that incorporation of MDPB into dentin primer could be beneficial for eliminating the residual bacteria in cavities.

Cytotoxic effects of composite restorations employing self-etching primers or experimental antibacterial primers.

OBJECTIVE: The aim of this study was to investigate the cytotoxic effects of composites which employ proprietary self-etching primers or experimental primers containing an antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) on human pulpal cells by in vitro dentine barrier tests. METHODS: Experimental primers were prepared by the addition of MDPB to each of two control proprietary primers at 1, 2 and 5%. Direct and indirect composite specimens were placed using each primer on one side of a dentine disk assembled in a simple pulp chamber device. Human pulp cells were incubated on the other side of the disk. After 48 h of incubation, the uptake of [3H]-thymidine by the cells was compared with that for negative controls using wax. Tests were repeated four times for each material. The diffusion of monomers from each specimen was determined using the same device. RESULTS: The specimens with control primers showed 26-35% reduction in cell activity. There were no significant differences in cytotoxicity between the control and experimental primers-specimens (Kruskal-Wallis test, p > 0.05). 2-Hydroxyethyl methacrylate at more than 1 mg ml-1 diffused from all specimens and was considered to be the cause of cytotoxic effects. The concentrations of MDPB diffused from the experimental primers-specimens were less than the toxic level, even for 5% MDPB-containing specimens. CONCLUSIONS: The results demonstrate that composites employing proprietary self-etching primers produced cytotoxic effects on human pulpal cells in vitro, although the toxicity was not severe. Incorporation of MDPB into a proprietary primer of up to 5% had no significant influence on the cytotoxicity observed.

Post-irradiation polymerization of composites containing bis-GMA and TEGDMA.

OBJECTIVE: This study was conducted to evaluate the effect of the amount of TEGDMA on post-irradiation polymerization of bis-GMA based composites. METHODS: Four experimental composites containing bis-GMA and TEGDMA at the ratios (w/w) of 75/25, 70/30, 67/33, and 50/50 were prepared. The degree of conversion of each composite was measured by Fourier transformation infrared spectroscopy immediately after being cured and after 24 h of storage, and the post-irradiation polymerization was determined. In addition, the change in respective amounts of residual bis-GMA and TEGDMA in cured specimens over 24 h was determined by high performance liquid chromatography. Data were analyzed by means of ANOVA, followed by a Fisher's PLSD test at a significance level of 0.05. RESULTS: At both stages of as-cured and after 24 h-sotrage, the composites containing greater amounts of TEGDMA showed a greater degree of conversion. The amount of post-irradiation polymerization decreased as the content of the incorporated TEGDMA increased. The reduction in the amount of TEGDMA remaining unreacted during post-irradiation polymerization also decreased as the content of TEGDMA increased, while the amount of unreacted bis-GMA showed almost constant values. SIGNIFICANCE: An increase in the amount of TEGDMA-incorporation in bis-GMA based composites resulted in less post-irradiation polymerization. As the change in the amount of residual unreacted TEGDMA in cured specimens showed the same trend as the results of the post-irradiation polymerization. TEGDMA is considered to be the main contributor to post-irradiation polymerization of bis-GMA based composites.

Bactericidal activity and cytotoxicity of antibacterial monomer MDPB.

The aim of this study was to investigate bactericidal characteristics and cytotoxicity of the newly developed antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB). To evaluate the bactericidal activity of MDPB against oral streptococci, the minimum bactericidal concentration (MBC) for seven species and time-kill kinetics against Streptococcus mutans were determined. The cytotoxic effects of MDPB on human pulpal cells were assessed by [3H]-thymidine uptake after contact with MDPB solutions at various concentrations. MDPB showed strong bactericidal activity against seven streptococci, the MBC value ranging from 31.1 to 62.5 micrograms ml-1. Time-kill determination indicated a rapid killing effect of MDPB at 250 micrograms ml-1 or over, and all cells were killed within 1 min by MDPB at 500 micrograms ml-1 or over. No cytotoxic effect was observed on contact with MDPB at concentrations of 10 micrograms ml-1 or less, and the toxicity of MDPB was considered to be similar to those of other monomers used for dental materials. These results suggest that MDPB can be effectively incorporated in dental resin-based materials to provide bactericidal activity against oral bacteria.

Second-line chemotherapy for relapsed small cell lung cancer.

Between January 1985 and August 1991, 159 patients with small cell lung cancer received first-line chemotherapy and 123 (77%) were responders. Of these, 88 relapsed, the remainder having died of other or unknown diseases or being alive without carrying cancer. The relapsed patients were examined to evaluate the outcome of the treatment for relapsed small cell lung cancer and to identify the factors that would contribute to the response rates and the survival durations. Forty-eight of 88 relapsed patients received second-line chemotherapy. Of the 48, 3 were evaluated as showing a complete response, 13 as partial response, 9 as no change, 15 as progressive disease and 8 as not evaluable. The response rate was 33% (95% confidence interval 20.4-48.4%). The median survival time was 146 days. The duration and rate of response in first-line chemotherapy affected the response rates of the second-line chemotherapy, but without statistical significance (P = 0.058 and 0.067 respectively). Increased response duration, time off chemotherapy and previous response to first-line chemotherapy all had a positive effect on the survival times (P < 0.01). Relapsed small cell lung cancer still shows a response to second-line chemotherapy without lessening survival time, and thus clinical trials of new drugs or combination chemotherapeutic regimens for relapsed small cell lung cancer cases would be reasonably justified. Randomized comparative studies are warranted for determining the benefits of second-line chemotherapy for relapsed small cell lung cancer cases.

Angiosarcoma of the heart presenting as fatal pulmonary hemorrhage.

A 47-year-old man died from fatal pulmonary hemorrhage. Cardiac angiosarcoma with lung metastases was found at postmortem examination. His chest radiograph showed bilateral, diffuse nodular infiltrates without cardiomegaly. No cardiac signs and symptoms were observed. The clinical outcome was rapidly fatal. Angiosarcoma of the heart should be suspected in patients with hemoptysis and nodular chest radiograph abnormalities, even in the absence of cardiac signs and symptoms.

Dose-intensive weekly chemotherapy for treatment of relapsed small-cell lung cancer.

PURPOSE: This study was undertaken to determine the activity and toxicity of dose-intensive weekly chemotherapy (cisplatin, vincristine, doxorubicin, and etoposide [CODE] regimen) for previous treated, recurrent small-cell lung cancer (SCLC). PATIENTS AND METHODS: The 17 patients with relapsed SCLC entered onto the study were to receive intensive weekly chemotherapy with the CODE regimen. All 17 patients had been heavily pretreated with some form of cisplatin-based combination chemotherapy. Six patients had received previous chemotherapy with CODE and one patient with cisplatin and etoposide (PE) as induction therapy. Nine patients had been treated with concurrent or sequential PE plus thoracic irradiation (TRT). The median time off chemotherapy was 6.7 months (range, 3.3 to 72). Patients were treated with 9 weeks of the CODE regimen. Response, survival, and toxicity data were noted. RESULTS: All 17 patients were assessable for response, survival, and toxicity. Fifteen of 17 patients (88.2%) had an objective response, with five complete responses (CRs; 29%) and 10 partial responses (PRs; 58.8%). The median durations of response and survival were 156 days and 245 days, respectively. Myelosuppression was significant, with 76% of patients developing grade 4 leukopenia. No treatment-related death was observed. CONCLUSION: The CODE regimen is highly active in the treatment of relapsed SCLC with an encouraging survival outcome.