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Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many cases without neutralizing activity or BI were immunosuppressed individuals. The results of this study show that BI occurs even when there are sufficient neutralizing antibodies in the blood due to exposure to close contacts at the time of infection. Thus, even after vaccination, sufficient precautions must be taken to prevent infection.

Objectives Unresectable stage III NSCLC (non–small cell lung cancer) confers a poor prognosis and interest is growing in the use of immunotherapy to improve outcomes for patients with this disease. We investigated the safety and efficacy of maintenance tecemotide, a mucin 1 (MUC1)-specific agent that induces T-cell responses to MUC1, versus placebo in Japanese patients with stage III unresectable NSCLC and no disease progression after primary chemoradiotherapy. Materials and methods Patients aged ≥20 years with unresectable stage III NSCLC, stable disease or clinical response after primary chemoradiotherapy and performance status ≤1, were recruited across 25 centers in Japan. Patients were randomized 2:1 to tecemotide (930 μg as lipopeptide) or placebo subcutaneously once weekly for 8 weeks, then every 6 weeks until disease progression or treatment withdrawal. Cyclophosphamide 300 mg/m2 (maximum dose 600 mg) was given intravenously 3 days before the first dose of tecemotide. The primary endpoint was overall survival (OS). Secondary endpoints were progression–free survival, time to progression, time to treatment failure and safety. Results The intent–to–treat population comprised 172 patients; 114 received tecemotide and 58 placebo. Baseline characteristics were comparable between treatment arms. Most patients (94%) received primary concurrent chemoradiotherapy. There was no apparent trend toward increased OS time with tecemotide over placebo (median 32.4 versus 32.2 months, hazard ratio 0.95, 95% confidence interval 0.61–1.48; P = 0.83). No improvements in secondary efficacy endpoints were observed. The frequency of treatment–related adverse events was similar, and serious adverse event rates were the same in both arms. There were no new safety signals. Conclusions These results do not support those from a randomized phase III study (START) of improved OS with tecemotide in the subgroup of patients treated with primary concurrent chemoradiotherapy.

Aim We conducted a retrospective study to investigate the frequency of appetite loss during treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in elderly patients, aged 75 years or older, with non-small cell lung cancer harboring EGFR gene mutations. Patients and methods Data of a total of 64 patients, including 39 relatively young (hereinafter, younger) patients and 25 elderly patients were analyzed. Results Appetite loss of all grades (p=0.074) and of grade 3 or greater (p=0.030) was more frequently observed in elderly patients. Diarrhea and oral mucositis were also more frequent in elderly patients, although they did not reach statistical significance. No apparent differences were observed in the frequency of aspartate aminotransferase/ alanine aminotransferase elevation, skin rash or fatigue between the two patient groups. The median (95% confidence interval) progression-free survival times were 10.8 (6.6-16.4) months and 11.8 (4.4-20.3) months in the younger and elderly patient groups, respectively. Conclusion Our findings suggest that appetite loss is a major adverse effect in elderly patients with non-small cell lung cancer receiving treatment with EGFR-TKIs.

This study aimed to provide a basis for appropriate home care for cancer patients by clarifying the usefulness of home visits in a collaboration program between visiting and certified hospital nurses. This was a mixed-methods study. (1) A quantitative study was conducted, involving all patients refe

Objective To determine whether the creatinine/cystatin C (Cr/CysC) ratio, which is influenced by muscle mass, can be used as a predictive marker of the adverse effects of chemotherapy. Methods This single-centre, retrospective, observational study assessed patients with lung cancer. Serum Cr and CysC levels were measured once within 1 month prior the commencement of chemotherapy. Results A total of 25 patients with lung cancer were enrolled in the study: 22 received first-line therapy; three received second-line therapy. A significant difference was noted regarding the Cr/CysC ratios between patients with nonsmall-cell lung cancer (NSCLC) and those with small-cell lung cancer (0.78 versus 0.92, respectively). A significant difference was also noted in the Cr/CysC ratios of patients with NSCLC with toxicity grades Conclusion The Cr/CysC ratio could serve as a useful predictive marker for chemotherapy-related adverse effects in patients with NSCLC.

Purpose Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate. Methods Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography. Results Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations. Conclusions These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.

Cortisol plays an important role in the physical status of patients with end-stage lung cancer, but the association of urine cortisol levels with TNM stage/performance status (PS) is unclear in patients with advanced lung cancer receiving chemotherapy. The objective of this study was to examine this association. In this single-center, retrospective, observational study, cortisol concentrations in 24-h pooled urine from 22 patients with advanced lung cancer were measured over 2 days. The mean concentration in each patient was compared with PS, TNM stage, and serum sodium and potassium ion levels. The 24-h urine cortisol levels were higher in PS2 or PS3 cases compared to PS1 (p

While systemic therapy is one of the therapeutic options available for post-operative recurrence of non-small cell lung cancer, efficacy of local therapy for locoregional recurrence or limited metastatic lesions has also been reported.We aimed to evaluate the clinical course of patients with post-operative recurrence(locoregional or limited metastatic lesion)after receiving local or systemic therapy.Clinical data were retrospectively analyzed and survival duration was compared using the logrank test.A total of 22 patients were included. Median progression-free survival in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies was 15.1 months, 6.3 months, and 13 months, respectively. Two patients receiving treatment with EGFR-TKI did not show disease progression at 41.3 months and 45.8 months(p=0.265). Median overall survivals in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies were 26.5 months, 20 months, and 37.9 months, respectively(p=0.510). After the treatment, 6 patients showed regrowth of the recurrent lesion, 8 patients showed remote metastases, and 2 patients showed both regrowth of the recurrent lesion and remote metastases.Patients who received treatment including local therapy showed longer survival duration, but statistical significance was not detected. Our study suggested that regrowth of the recurrent lesion and remote metastases can be equally observed after treatment.

We report a patient with liver metastasis from rectal cancer who developed interstitial pneumonia during regorafenib administration. The patient described herein was a 69-year-old female. In January 2011, she underwent low-position anterior resection of rectal cancer at another hospital. In May 2013, right iliac metastasis was detected and she was referred to our hospital. Radiotherapy (30 Gy) was performed to treat bone metastasis and pain was relieved. Ursodeoxycholic acid (300 mg/day) and a glycyrrhizic acid/glycine/l-cysteine injection (20 mL/day) were subsequently administered. In July 2013, the administration of regorafenib (160 mg/day) was initiated and computed tomography (CT) was performed every week. CT revealed the appearance of diffuse ground-glass opacities in the bilateral lungs 13 days after starting the administration of regorafenib. Steroid pulse therapy was started following a tentative diagnosis of regorafenib-related interstitial pneumonia, which resulted in the amelioration of the ground-glass opacities. Although there has been no case report on interstitial pneumonia in a clinical study prior to approval, interstitial pneumonia developed during the administration of regorafenib in the present case. As steroid therapy improved the patient’s condition and CT findings, the patient was diagnosed with regorafenib-related interstitial pneumonia. Prompt management, such as steroid therapy, may be important when interstitial pulmonary disorders are detected during the administration of regorafenib.

Aim: To examine the feasibility and usefulness of a novel region-based pathway: the Regional Referral Clinical Pathway for Home-Based Palliative Care. Method: This was a feasibility study to evaluate the frequency of variances and the perceived usefulness of pathway using in-depth interviews. All patients with cancer referred to the palliative care team between 2011 and 2013 and received home care services were enrolled. Result: A total of 44 patients were analyzed, and pathway was completed in all the patients. The target outcome was achieved in 61.4% while some variances occurred in 54.5%. Nine categories were identified as the usefulness of the pathway, such as reviewing and sharing information and promoting communication, education, motivation, and relationships. Conclusion: This novel pathway is feasible and seems to be useful.

The purpose of our study was to retrospectively evaluate the clinical efficacy and safety of laparoscopy assisted distal gastrectomy (LADG) performed by one operating and advising surgeon in patients with gastric cancer over a period of 10 years. We examined the choice of anastomosis techniques, and compared the duration of surgery, blood loss, number of dissected lymph nodes and intraoperative complications for LADG and open distal gastrectomy (ODG). We studied 254 patients who underwent laparoscopic gastrectomy and 36 patients who underwent ODG. 169 of 254 patients received LADG. Duration of surgery was significantly longer for LADG than that for ODG, blood loss was significantly smaller, and numbers of dissected lymph nodes were similar. With LADG, there was anastomotic leakage in 2 patients and postoperative obstruction in 2 patients. No recurrence of disease and no deaths have been reported to date. Though previous clinical trials have shown that LADG is less invasive, our study of LADG in the real world did not show superiority, but rather equivalence to ODG in terms of other outcomes. This study could be advantageous to evaluate the clinical efficacy and safety of LADG without having to take into account multiple surgeons’ technical levels and the background differences between the facilities.

Laparoscopy-assisted distal gastrectomy (LADG) has become one of the standard surgical procedures for gastric cancer in Japan and Korea. However, LADG is currently listed as being in the clinical research phase under the Gastric Cancer Treatment Guidelines. The aim of this study is to report surgeons’ opinions of what is needed if LADG is to become a standard procedure. We conducted questionnaire survey with open questions in hospitals that either applied or did not apply LADG and compared the answers. We labeled and categorized the collected data using content analysis. The number of hospitals which applied LADG more than doubled from 5 to 12 hospitals over 3 years. Overall, hospitals reported that the necessary elements for LADG to become a standard procedure are: clinical trials of LADG (n = 5, 22.7%), surgeons’ practical experience in performing LADG (n = 4, 18.2%), stability of radical treatment (n = 4, 18.2%), and a shorter operative duration (n = 3, 13.6%) for the procedure. Surgeons’ practical experience was chosen as the most important requirement in the hospitals which applied LADG while clinical trials (n = 2, 40.0%) and stability of radical treatment (n = 2, 40.0%) were the most common answers in the hospitals which did not apply LADG. Hospitals and surgeons’ practical experience, stabilizing radical cure, and the large scale of clinical trials are for LADG to become a standard procedure and to gain equivalent importance as open distal gastrectomy in treating gastric cancer.

Background Taxanes are known to cause onychopathy. Previous studies have reported the relationship between onychopathy and paclitaxel dosing intervals and cumulative doses. However, there are no studies of the predictive factors for docetaxel-induced nail changes. The present study used the drug accumulation rate (mg/m2/day) as a novel indicator and evaluated its usefulness for the prediction of onychopathy. Methods From January 2008 to December 2009, we examined patients who received docetaxel at the Toyama University Hospital and Tonami General Hospital to determine the time to onset of onychopathy, the accumulation rate, and the cumulative dose. We then divided the study subjects into two groups, and used Receiver Operating Characteristic (ROC) analysis to calculate a cut-off value. We evaluated both indicators as predictive factors for onychopathy using the log-rank test and Cox proportional hazards model. Results Ninety-five patients were included in the present study. The results of the log-rank test sub-analysis revealed that the median number of days until onychopathy onset was significantly shorter in patients with an accumulation rate greater than the cut-off (P = 0.009), and in those with a cumulative dose below the cut-off (P

Background: Approximately 70% of the patients who receive chemotherapy suffer from fatigue, which lowers their quality of life and also has a negative influence on therapeutic efficacy. Previous studies have suggested a relationship between blood carnitine levels and fatigue. We conducted a prospective observational study to examine the relationship between carnitine pharmacokinetics and chemotherapy-induced fatigue in patients receiving cancer chemotherapy regimens that include cisplatin. Patients and Methods: 11 patients receiving chemotherapy including cisplatin (60-80 mg/m2) were included in the study. We performed 24-h urine collections and took blood samples on day 1 (before the initiation of chemotherapy) and days 2, 3, 4, and 8 in order to measure the carnitine concentrations in the serum and urine. These were compared with measures of self-reported fatigue. The primary endpoint was the change in self-reported fatigue subscales from baseline to day 8. Results: Urinary carnitine concentrations differed significantly on days 2 and 3 (p = 0.003). The Functional Assessment of Chronic Illness Therapy-Fatigue scale version 4A score on day 8 indicated significantly higher levels of fatigue as compared to day 1 (p = 0.013). Conclusion: This study suggests that there is an association between urinary carnitine levels and self-reported fatigue.

PurposeGefitinib is a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase. We conducted a phase III trial to evaluate whether gefitinib improves survival as sequential therapy after platinum-doublet chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC).Patients and MethodsChemotherapy-naïve patients with advanced stage (IIIB/IV) NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ function were randomly assigned to either platinum-doublet chemotherapy up to six cycles (arm A) or platinum-doublet chemotherapy for three cycles followed by gefitinib 250 mg orally once daily, until disease progression (arm B). Patients were stratified by disease stage, sex, histology, and chemotherapy regimens. The primary end point was overall survival; secondary end points included progression-free survival, tumor response, safety, and quality of life.ResultsBetween March 2003 and May 2005, 604 patients were randomly assigned. There was a statistically significant improvement in progression-free survival in arm B (hazard ratio [HR], 0.68; 95% CI, 0.57 to 0.80; P < .001); however, overall survival results did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.03; P = .11). In an exploratory subset analysis of overall survival by histologic group, patients in arm B with adenocarcinoma did significantly better than patients in arm A with adenocarcinoma (n = 467; HR, 0.79; 95% CI, 0.65 to 0.98; P = .03).ConclusionThis trial failed to meet the primary end point of OS in patients with NSCLC. The exploratory subset analyses demonstrate a possible survival prolongation for sequential therapy of gefitinib, especially for patients with adenocarcinoma.

The objective of this phase I/II study was to determine the recommended dose (RD) of S-1 and carboplatin (CBDCA), and to evaluate the efficacy and safety of this combination in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients were treated with S-1 given orally on days 1-14, and CBDCA infused intravenously on day 1, repeated every 3 weeks. RD was AUC5 of CBDCA and 80 mg/m(2) of S-1. Nineteen patients were treated at the RD. The overall response was 30.8% (95% confidence interval: 17.1-58.3%). The response rate in the RD was 36.8% (95% CI: 16.3-61.6%). The median overall survival time was 11.1 months (95% CI: 8.1-15.3 months) and the median progression-free survival time was 5.0 months (95% CI: 3.6-6.0 months). Major grades 3-4 toxicities were thrombocytopaenia (47%), anaemia (26%) and infection (16%). This is the first report to show promising activity of this combination in phase II, including survival data and manageable toxicity, especially in outpatients receiving treatment for advanced NSCLC.

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.

Treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been shown to prolong survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). The present study performed a retrospective analysis to investigate the association between the plasma lactate dehydrogenase (LDH) levels and survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. The medical charts of patients with EGFR mutation-positive NSCLC who were receiving treatment with EGFR-TKIs at Toyama University Hospital between 2007 and 2014 were assessed. The data from 65 patients were included in the analysis. Patients with higher plasma LDH levels exhibited shorter progression-free survival (6.2 vs. 13.2 months; P, 出版社サイトへのリンク：https://doi.org/10.3892/mco.2016.779

In Japan, palliative home care is subject to increasing demand from patients. However, the number of deaths at home is still not as high as that of palliative home care users.This study aimed to clarify factors influencing the place of death and home care rates, involving end-stage cancer patients targeted for palliative care by a general home-visit nursing agency.A total of 87 patients who had used palliative home nursing care services provided by the study facility within a 6-year period after its opening were studied.The numbers of deaths at home supported by family physicians and those in hospital after readmission were 70 and 17, respectively. The numbers of deaths at home using services provided by the study facility and nurses belonging to it time-dependently increased, revealing a strong correlation between them. Furthermore, the place of death and home care rates were closely associated with the mean duration of home nursing services and home visits in collaboration with family physicians in charge.These results suggest that it may be possible to increase the rate of home care for end-stage cancer patients and meet their desires regarding the place of death through approaches to establish trust-based relationships with them and their families, such as strengthening manpower in home-visit nursing agencies and promoting collaboration between visiting nurses and family physicians in charge during home visits.

Aims and Background Amrubicin monotherapy can be an effective treatment option for patients with recurrent small cell lung cancer (SCLC). We conducted this retrospective study to investigate the prognostic factors in patients with recurrent SCLC receiving amrubicin monotherapy. Methods The associations between survival and clinical data, including the performance status, body mass index (BMI), plasma lactate dehydrogenase (LDH) level, and plasma neuron-specific enolase level, were evaluated in patients with recurrent SCLC, and a subset analysis of patients with platinum-resistant disease was conducted. Results In all, 37 patients were evaluated. The median survival from the date of initiation of amrubicin monotherapy was 9.1 months (95% confidence interval 4.7–12.0 months). Multivariate analysis using a Cox proportional hazard model identified the plasma LDH level (p = 0.049), BMI (p = 0.031), and platinum resistance (p = 0.032) as independent factors associated with survival. The same associations were also observed in the subset of patients with platinum-resistant disease. Conclusions Our findings suggest that the plasma LDH level and BMI may be useful prognostic factors in patients with SCLC receiving amrubicin monotherapy, including patients with platinum-resistant disease.

Determination of the presence of epidermal growth factor receptor (EGFR) gene mutation is useful for predicting the efficacy of gefitinib. However, the survival rate following the initiation of treatment with gefitinib varies among individuals. A retrospective study was conducted to investigate the associations of the pretreatment serum pro-gastrin-releasing peptide (pro-GRP) and plasma neuron-specific enolase (NSE) levels to the patient survival rate following initiation of treatment with gefitinib in non-small cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients with NSCLC harboring EGFR gene mutations who received gefitinib therapy between 2004 and 2012 were included in the study. Data from a total of 41 patients were analyzed. The serum pro-GRP level was measured in 31 patients and the plasma NSE in 22 patients. The progression-free survival (PFS) (P=0.013) and overall survival (OS) (P=0.014, log-rank test) rates decreased as the plasma NSE level increased. Statistical analysis using a Cox proportional hazards regression model adjusted for age, gender, performance status (PS) and disease stage showed that higher NSE levels were associated with shorter PFS (P=0.021) and OS (P=0.0024). By contrast, no association was detected between the serum level of pro-GRP and survival rate. The results suggest that pretreatment NSE measurement could be clinically useful in patients with NSCLC scheduled to receive gefitinib treatment., 出版社サイトへのリンク: https://doi.org/10.3892/mco.2015.568

Background The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor ( EGFR ) mutation status. Methods Japanese chemotherapy-naive NSCLC patients were enrolled. They had measurable lesions, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ and bone marrow function. Patients received 250 mg of oral gefitinib daily. EGFR mutations in exon 18, 19, and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence. Results All 30 patients were eligible for the assessment of efficacy and safety. An objective response and stable disease were observed in 10 patients (33.3%) and nine patients (30.0%), respectively. The median time to progression was 3.3 months and the median overall survival was 10.6 months. The 1-year survival rate was 43.3%. Grade 3 toxicities were observed in seven patients. EGFR mutation was observed in four of 13 (30.8%) tumors, and two of them achieved partial response. In serum samples, three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib. EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment samples from patients with a partial response or stable disease than in those from patients with progressive disease ( p = 0.006). Conclusions Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active, with acceptable toxicities. These results warrant further evaluation of gefitinib monotherapy as a first-line therapy. The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment.

BACKGROUND. Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. METHODS. One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. RESULTS. Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). CONCLUSIONS. Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study. Cancer 2006. © 2006 American Cancer Society.

Background: The A to C transversion in the promoter region of the gene encoding leukotriene C 4 synthase (LTC4S) is proposed to be associated with the development of aspirin-induced asthma (AIA). Objective: We investigated the frequency of the polymorphism in Japanese population and its association with clinical characteristics and cysteinyl leukotriene production. Methods: Genotyping of LTC4S gene promoter was performed on 60 patients with AIA, 100 patients with aspirin-tolerant asthma (ATA), and 110 control subjects. We assessed the basal levels of urinary LTE 4 , the increment of urinary LTE 4 on venous aspirin challenge, and LTC 4 S activity in peripheral blood eosinophils. Results: The frequency of the variant C allele was significantly higher in patients with AIA (frequency of allele [q] = 0.192) than in patients with ATA (q = 0.110, P = .042). Variant C-allelic carriers experienced asthma at a significantly younger age (31.8 ± 2.9 years [mean ± SEM]) than wild-type A homozygotes (41.3 ± 2.2 years, P = .007). Basal levels of LTE 4 and the increment of urinary LTE 4 on venous aspirin challenge did not show a difference between wild-type A homozygotes and variant C-allelic carriers. There was no relationship between the polymorphism and the LTC 4 S activity in eosinophils, although LTC 4 S activities were significantly higher in patients with AIA than in patients with ATA. Conclusion: Our findings reveal the lack of functionality of the polymorphism in the LTC4S gene, whereas this polymorphism might have some effect on the development of AIA, probably in linkage disequilibrium with another causatively important mutation. (J Allergy Clin Immunol 2002;109:936-42.)

e21665 Background: The oral transmucosal fentanyl disintegrating tablet, Abstral, is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid onset analgesia, and which may be effective for breakthrough cancer pain. It can be administered for the patients who cannot take the oral medicine. It has been marketed since 2014 in Japan. Methods: We selected patients who were administered Abstral for breakthrough cancer pain between 2014 and 2016 at Toyama University Hospital in Japan. We retrospectively investigated administration reasons based on medical record of those patients. Results: There were 111 patients who were administered Abstral. Primary lesions of lung/Gastrointestin/others were 43/52/16, respectively. ECOG PS 0-2/3-4 were 27/84, respectively. The median age was 66 y.o. (range 35-91 y.o.). Regularly using opioid were fentanyl patch prescribed for all patients. Median dose of fentanyl patch was 25mcg/hr (range 12.5-250mcg/hr). 90 patients (81%) had difficulties in the administration of oral medicine, which was the main reason of Abstral administration. Four patients (4%) were to reduce constipation and vomiting as side effects of oxycodone. Seven patients (6%) were to start a fentanyl patch. Three patients (3%) were assessed poor effect for short-acting opioid. Only seven patients (6%) were expected of rapid onset of analgesia effect. Abstral was administered in 27 patients (24%) during aggressive treatment such as chemotherapy administration and in 84 patients (76%) after aggressive treatment. Conclusions: The oral transmucosal fentanyl was administered for the patients who cannot take the oral medicine in Japan while it is expected to be administered to those who want to relieve breakthrough pain fast. Affirming a common understanding of the efficacy of the oral transmucosal fentanyl and breakthrough cancer pain is necessary in Japan.

It is reported that about 20% of patients with small cell lung cancer (SCLC) receive third-line chemotherapy. We conducted a retrospective study to investigate the outcome and prognostic factors of patients with SCLC who receive third-line chemotherapy.The medical records of patients with SCLC who received third-line chemotherapy at our institution were reviewed. Overall survival (OS) from the initiation of third-line chemotherapy was evaluated, and the association between OS and patient characteristics was assessed by the log-rank test.A total of 73 patients with SCLC were treated with cytotoxic drugs between 2004 and 2012, and 19 patients received third-line chemotherapy. Median OS from initiation of third-line chemotherapy was 8.5 months. Patients with higher body mass index (BMI) (P = 0.0071), lower levels of lactate dehydrogenase (LDH) (P = 0.0036), higher levels of hemoglobin (P = 0.048), longer time to progression (TTP) from the initiation of second-line treatment (P = 0.0036), and better response to second-line treatment (P = 0.029) had longer duration of OS.It is suggested that TTP and tumor response in second-line chemotherapy, serum levels of LDH and hemoglobin, and BMI at initiation of third-line chemotherapy could be possible prognostic factors.

The efficacy of docetaxel, vinorelbine, or gemcitabine monotherapy in previously untreated elderly patients with non-small cell lung cancer has been reported.Pemetrexed monotherapy has shown clinically equivalent efficacy to docetaxel, a standard therapeutic option, in patients with previously treated non-small cell lung cancer and in those with a lower incidence of toxicity such as febrile neutropenia.In the present study, we aimed to investigate the efficacy and toxicity of pemetrexed in previously untreated elderly patients with non-squamous cell lung cancer and compare the results with those of docetaxel, considered a standard chemotherapeutic agent.We retrospectively reviewed the medical records of patients with non-squamous cell lung cancer with wild-type(or unknown)epidermal growth factor receptor status who received pemetrexed or docetaxel monotherapy as first-line chemotherapy.We analyzed 6 patients with lung adenocarcinoma in the pemetrexed group and 6 patients with lung adenocarcinoma in the docetaxel group. The median progression-free survival was 3.6 months for patients receiving pemetrexed and 3.1 months for those receiving docetaxel(p=0.45). The median overall survival was 14.8 months in the pemetrexed group and 10.9 months in the docetaxel group(p=0.36).Patients who received docetaxel were more likely to have grade 3 or 4 neutropenia and febrile neutropenia than those receiving pemetrexed.However, 2 patients who received pemetrexed showed grade 3 pneumonitis.Pemetrexed monotherapy is a promising treatment for previously untreated elderly patients with non-squamous cell lung cancer.

The usefulness of the Palliative Prognostic Index (PPI) has been successfully validated in a variety of clinical settings. However, while lung cancer is the leading cause of death worldwide, patients with lung cancer accounted for only 6.9-25.8 % of the study populations in these previous studies. We conducted a retrospective study to evaluate the usefulness of the PPI for survival prediction in patients with lung cancer. Patients with lung cancer who were admitted to our hospital between 2009 and 2013 to receive palliative care were enrolled. The association between the Palliative Prognostic Index, determined based on the data recorded in the clinical charts at the last admission to our hospital, and survival was evaluated. The patient group with a PPI of >6 showed a significantly shorter survival time than the patient group with a PPI of ≤ 6 (P < 0.0001, log-rank test). The sensitivity and specificity of the PPI determined using the cutoff value of 6 for predicting less than 3 weeks of survival were 61.3 and 86.8 %, respectively. However, the sensitivity decreased to 50.0 % when the assessment was carried out in only patients with small cell lung carcinoma. Our findings suggest the existence of a close association between the PPI and survival in patients with lung cancer receiving palliative care. However, the sensitivity of the index for predicting less than 3 weeks of survival was relatively low in patients with small cell lung carcinoma.

Radiation pneumonitis is a major complication of radiation therapy. However, the detailed cellular mechanisms have not been clearly defined. Based on the recognition that basement membrane disruption occurs in acute lung injury and that matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components of the basement membrane, we hypothesized that ionizing radiation would modulate MMP-2 production in human lung epithelial cells. To evaluate this, the modulation of MMP-2 with irradiation was investigated in normal human bronchial epithelial cells as well as in A549 cells. We measured the activity of MMP-2 in the conditioned medium with zymography and the MMP-2 mRNA level with RT-PCR. Both of these cells constitutively expressed 72-kDa gelatinolytic activity, corresponding to MMP-2, and exposure to radiation increased this activity. Consistent with the data of zymography, ionizing radiation increased the level of MMP-2 mRNA. This radiation-induced increase in MMP-2 expression was mediated via p53 because the p53 antisense oligonucleotide abolished the increase in MMP-2 activity as well as the accumulation of p53 after irradiation in A549 cells. These results indicate that MMP-2 expression by human lung epithelial cells is involved in radiation-induced lung injury.

The number of elderly patients with lung cancer is increasing. This study was undertaken to assess the validity of pneumonectomy for the treatment of lung cancer in this patient group.Twenty-seven patients 70 years old or older (elderly group) and 95 patients younger than 70 years (younger group) who underwent pneumonectomy between January 1985 and March 1996 formed the study group. In the elderly group, 22 patients had squamous cell carcinoma, 2 had adenocarcinoma and 3, small cell carcinoma; 1 patient was in postoperative stage I, 4 patients were in stage II, 14 in stage IIIA, 5 in stage IIIB, and 3 in stage IV of the disease. The only significant differences in patient characteristics between the two groups were the percentage of patients undergoing right pneumonectomy and the percentage of patients receiving chemotherapy or radiotherapy within 3 months before or after operation or both times.The prognosis for the elderly group was comparable to that of the younger group for all stages of the disease; the overall 5-year survival rate was 30.5% for the younger group and 11.5% for the elderly group. However, operation-associated mortality was significantly higher in the elderly group (22.2% versus 3.2%; p0.005). The prognosis was better for patients with a centrally located tumor than a peripheral tumor in both groups [13.5% versus 2.0% in the elderly group and 46.7% versus 5.2% (p0.01) in the younger group] and significantly better for patients having a left pneumonectomy than a right pneumonectomy in the younger group (46.7% versus 5.2%; p0.01) but not in the elderly group (13.7% versus 22.2%). Adjuvant treatment did not have any beneficial effect on the prognosis in either group.Pneumonectomy for lung cancer in elderly patients appears to be justified because the outcome in our study was comparable with that for the younger patients. However, it should be performed only in carefully selected patients because of the increased operative risk.

This study was undertaken to evaluate whether the therapeutic effect of pranlukast, a selective cysteinyl leukotriene (LT) C4/D4/E4 receptor antagonist, can be observed in patients with the non-atopic or atopic type of asthma, or in asthmatics taking oral steroids. Twenty-two patients with moderate to severe bronchial asthma receiving an inhaled corticosteroid (beclomethasone dipropionate) were treated with pranlukast (225 mg b.i.d.) for 4 weeks, and their peak expiratory flow (PEF) and asthmatic symptoms were monitored during the treatment period. In the patients with the non-atopic type of asthma (n = 13), an increase in their PEF was observed both in the morning and evening following a 4-week administration of pranlukast, but the degree was slightly inferior to that in patients (n = 9) with the atopic type of asthma. On the other hand, no significant increase was observed in the patients (n = 6) taking oral prednisolone (PSL, 5–15 mg/day). Changes in the symptom score at the end of the 4-week treatment period were closely associated with those in the PEF values; namely, a significant improvement in symptom score was observed for patients with the atopic and non-atopic type of asthma, but no improvement for the patients taking oral PSL. Pranlukast, a selective LT receptor antagonist, will be a valuable asset in the treatment of bronchial asthma, especially asthma requiring no oral steroids.

Background : Cysteinyl leukotrienes (LTs) and thromboxane A2 (TXA2) are known to play an essential role in the pathogenesis of atopic asthma. However, their rol

To assess the role of pneumonectomy for lung cancer and the factors affecting the prognosis, 107 patients who had undergone pneumonectomy for non-small cell lung cancer (NSCLC) between January, 1985 and March, 1996, were analyzed. They included 81 squamous cell carcinoma, 22 adenocarcinoma, 3 large cell carcinoma, and one adenosquamous cell carcinoma, with 8 patients in post-operative stage I, 15 in stage II, 51 in stage IIIA, and 33 in stage IIIB of the disease. The 5-year survival rate was 54.7% in stages I + II, 38.0% in stage IIIA, and4% in stage IIIB. In stages I-IIIA, the patients with squamous cell carcinoma showed a significantly better prognosis than those with adenocarcinoma (50.6 vs. 0%, p0.01). The prognosis was also better, but not statistically significant, for patients with central type compared with those with peripheral type in both all histologic types (58.0 vs. 8.4%) and only squamous cell type (59.3 vs. 18.8%). A better prognosis observed in squamous histologic type or central type seemed to be related to a better N factor. Pneumonectomy remains the treatment of choice for lung cancer, but seems not to be justified for patients with stage IIIB due to their poor prognosis.

In order to define the roles of the K-ras and p53 genes in the development of lung cancer, especially in young adults, we compared the clinicopathological features of the patients between younger (< or = 45 years, n = 47) and older (< 55 years, n = 50) groups. The gene alterations were examined by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method. The K-ras gene alterations were detected only in adenocarcinomas, and the p53 gene alterations in all histologic types of lung cancer. There were no significant differences in the frequency of both K-ras and p53 gene alterations between the younger and older groups (9 vs. 11%, 36 vs. 32%). In the younger group, but not in the older one, the percentage for smokers was significantly higher in the p53 gene alteration-positive group than for the negative group (65 vs. 30%). As to the prognosis, there were no significant differences between the p53 gene alteration-positive and -negative cases in both the younger and older groups as well as in all subjects, while a tendency of poorer prognosis was observed in K-ras gene alteration-positive cases than for the -negative ones with adenocarcinomas. These results suggest that (1) the K-ras and p53 gene alterations would have no special roles in terms of the lung carcinogenesis in young adults; (2) a positive relationship between smoking and p53 gene alteration would exist in young adults with lung cancer, and (3) K-ras gene alteration would become a prognostic factor in lung cancer.

Introduction Miliary brain metastasis is an extremely rare form of brain metastasis which can present with atypical imaging findings. We report the case of a patient with miliary brain metastasis of lung cancer showing calcification in metastatic lesions. Case presentation A 68-year-old Japanese woman was diagnosed with lung adenocarcinoma. Brain computed tomography revealed multiple small calcified lesions in both cerebral hemispheres. Mutation of the epidermal growth factor receptor gene (exon 21, L858R) in lung cancer cells was detected, and treatment with gefitinib was initiated. A partial response was observed; however, the patient was readmitted to our hospital because of regrowth of the primary lesion and complaints of nausea, headache, and difficulty walking. Brain magnetic resonance imaging revealed scattered tiny nodules enhanced by gadolinium. A diagnosis of leptomeningeal carcinomatosis was made on the basis of cerebrospinal fluid cytology. The patient’s general status worsened, and she died 356 days after the day of first medical examination. Upon autopsy, the brain was found to be edematous and swollen. Lung carcinoma cells were diffusely disseminated on the meningeal surface. Metastatic foci of small nodular form, accompanied by calcifications, were also found in the brain parenchyma. We diagnosed miliary metastasis of lung carcinoma. Conclusions To the best of our knowledge, this is the third report of calcified miliary brain metastasis confirmed by autopsy. We describe calcified lesions that increased in size during the clinical course of nine months. Brain computed tomography findings that reveal multiple small calcified lesions in patients with malignancy should raise suspicion of miliary brain metastasis.

A 23-year-old man was admitted for examination of an abnormal shadow in the right lower lung field. A chest CT scan revealed a nodule in the right lower lobe and a calcified nodule in the right upper lobe. A diagnosis of lung adenocarcinoma in the right lower lobe was made by transbronchial cytology. After resection of the right lower lobe and partial resection of the nodule in the right upper lobe were performed, we diagnosed lung adenocarcinoma in the right lower lobe (pathological stage IIIA) and hamartoma in the right upper lobe. Although several authors have reported cases of synchronous pulmonary hamartoma and lung cancer, it is uncommon in young patients. Since patients with hamartoma could also have lung carcinoma, careful observation is needed.

We report 2 cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma. Case 1: A 69 year-old man presented, complaining of right chest pain. The chest X ray film and CT showed tumors in the right chest wall and pleura. Histological findings of specimens obtained from a percutaneous biopsy revealed spindle tumor cells, and the immunohistochemistry showed that the tumor cells were positive for CK-7, AE1/AE3, and vimentin and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel, but it was ineffective. Case 2: A 68 year-old man was admitted complaining of general malaise. The chest X ray film and CT revealed tumors in the right chest wall. Histological findings showed necrosis and spindle tumor cells which were positive for AE1/AE3 and vimentin, and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel. However the disease continued to progress and he died 2 months after admission. The pulmonary sarcomatoid carcinoma was reported to have spred to the pleural and chest wall. The present two cases showed prominent chest wall and pleural tumors with obscure primary lung tumors. Therefore, we needed to differentiate sarcomatoid carcinoma from malignant pleural mesothelioma.

The myelorestorative effects of granulocyte colony-stimulating factor (G-CSF), interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6) were studied in F-344 rats which had been treated with cyclophosphamide (CY), carboplatin (CBDCA), or nimustine hydrochloride (ACNU). In CY- or CBDCA-pretreated rats, significantly higher peripheral white blood cell (WBC) count was observed in animals treated with G-CSF and IL-1 alpha, while the platelet (PLT) count was elevated by IL-6 treatment. All of the cytokines had little effect on the hemoglobin (HB) value. Animals treated with ACNU had prolonged myelosuppression. Treatment of these animals with G-CSF and IL-1 alpha significantly enhanced the recovery of HB value as well as WBC count. Higher PLT counts were observed in treated groups, but a statistical difference was not evident. Combination therapy with G-CSF and IL-1 alpha, G-CSF and IL-6, or IL-1 alpha and IL-6 did not have any significant beneficial effects on the peripheral blood cell count in ACNU-pretreated rats over single agent therapy. Conversely, the combination of IL-6 and G-CSF had an unfavorable effect on HB and PLT levels. In rats which received multiple doses of ACNU, G-CSF treatment exhibited a beneficial effect on WBC, HB, and PLT levels, the most prominent on the HB value. These findings suggest that treatment with hematopoietic cytokines may be most beneficial when combined with anticancer drugs which are known to cause prolonged myelosuppression.

Introduction: A phase I study on relapsed small cell lung cancer (SCLC) was conducted to establish the toxicity and maximum tolerated dose of carboplatin with topotecan, and to observe the antitumor activity. Methods: Thirty-two SCLC patients who had received one previous line of chemotherapy were enrolled. Topotecan was infused for 30 minutes on days 1 to 5, and carboplatin for 60 minutes after the topotecan infusion on day 5 every 3 weeks. Granulocyte colony-stimulating factor prophylaxis was administered from day 8 to white blood cell or neutrophil recovery. Results: The most frequent toxicities were neutropenia and thrombocytopenia. Nonhematological toxicities were generally mild. Three of six patients experienced a dose-limiting toxicity, thrombocytopenia, at dose level 6: 0.85 mg/m 2 topotecan with area under curve 5 carboplatin (maximum tolerated dose). Of 29 evaluable patients, 5 (17.2%) had partial responses. Of 21 patients who relapsed more than 90 days after completion of first-line chemotherapy, 5 (23.8%) had partial responses. Median overall survival time and 1-year survival rate were 11.3 months and 50.0%, respectively. Conclusions: The recommended dose for further studies is 0.75 mg/m 2 of topotecan on days 1 to 5 with area under curve 5 of carboplatin on day 5 every 3 weeks. This combination is well tolerated, and is promising for sensitive relapsed SCLC. A comparative study against single-agent topotecan for sensitive relapsed SCLC is warranted.

A survey regarding the revelation of the diagnosis of cancer to patients was conducted on 116 medical doctors (MD), 206 paramedical personnel (PP) and 789 lay persons (LP) in June 1989 in Toyama prefecture, Japan. When asked in the case that their parents or spouse had cancer, only 29.8% of all respondents answered that they would reveal the diagnosis of cancer to their family member. On the contrary, if they themselves had cancer, 56.3% of all respondents answered that they wished the diagnosis to be revealed, and 77.4% of these answered that they wished to be informed of the cancer diagnosis by the doctor in charge. They wanted to know the details of their condition from their medical doctor, and thought that they could receive this knowledge calmly. Thirty-one percent (34/108) of the doctors questioned reveal the diagnosis of cancer to their patients and 79.4% of these answered that they felt that telling the true diagnosis was good. A serious responsibility for the medical doctor was indicated.

A 49-year-old woman noticed hoarseness and facial palsey three months prior to her visit to our hospital. Chest radiograph and CT scanning revealed bilateral mediastinal and hilar lymphadenopathy. Bronchofiberoptic biopsy showed sarcoidosis. Her symptoms improved under no treatment. However, she showed rapid increase of mediastinal and abdominal lymph nodes swelling and elevation of serum level of sIL-2R during observation. Therefore, we must discriminate sarcoidosis-lymphoma syndrome from exacerbation of sarcoidosis. Mediastinoscopic biopsy was conducted for diagnosis, and it revealed exacerbation of sarcoidosis. We reported this rare case of rapid increase of mediastinal and abdominal lymph node swelling due to sarcoidosis.

A 45-year-old man was admitted to our hospital with high-grade fever uncontrolled by antipyretic drugs, and elevation of the serum LDH and sIL-2R levels, and decrease of diffusing capacity for carbon monoxide. Chest computed tomography (CT) showed no abnormal findings but 67Ga scintigraphy revealed diffuse pulmonary uptake. He was given a diagnosis of intravascular lymphomatosis (IVL) based on transbronchial lung biopsy (TBLB) and immunohistochemical analysis. The prognosis of IVL is generally bad, because antemortem diagnosis is difficult. In this case early TBLB enabled satisfactory curative effect of IVL.

e20545 Background: A large majority of patients who receive chemotherapy suffer from fatigue, which lowers their QOL and activities and also has a negative influence on therapeutic efficacy. Althou...