Primary Squamous Cell Lung Cancer With Frequent Episodes of Sustained Ventricular Tachycardia due to Myocardial Metastasis.

Myocardial metastasis from lung cancer rarely occurs. We encountered a patient with squamous cell lung cancer who was diagnosed with myocardial metastasis before death and sustained ventricular tachycardia during the course of the disease. The patient was a 56-year-old woman. A tumor was noted in the apex area of the left lung and was diagnosed as stage IVA of squamous cell lung cancer after a detailed examination. She underwent concurrent chemoradiotherapy with weekly treatment of carboplatin + paclitaxel. A 12-lead electrocardiogram performed upon admission for additional chemotherapy showed negative T waves in leads III, aVF, and V1-4. Transthoracic echocardiography and computed tomography showed a tumor lesion in the right ventricular wall, which was diagnosed as myocardial metastasis from lung cancer. During the course of the disease, the patient had frequent episodes of sustained ventricular tachycardia, which were refractory to treatment with antiarrhythmic drugs. However, the sinus rhythm was restored with cardioversion. Subsequently, the patient received palliative treatment and eventually died 4 months after the diagnosis of cardiac metastasis and 3 weeks after the diagnosis of ventricular tachycardia. Myocardial metastasis might reflect poor prognosis due to serious arrhythmia or some other complications. Therefore, the early diagnosis and appropriate treatment of cardiac metastasis by chemotherapy, cardiac radiotherapy, or surgery, are necessary prior to the development of symptoms in tolerant cases.

Efficacy of cisplatin plus vinorelbine adjuvant chemotherapy with split-dose administration of cisplatin after complete resection of stage II-IIIA non-small cell lung cancer.

Although co-administration of cisplatin (CDDP) and vinorelbine (VNR) has been established as a standard of care adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is a lack of clinical data on its safety and efficacy in Japanese patients receiving split-dose administration of CDDP. The present study analyzed patients who received CDDP + VNR with split-dose administration of CDDP after undergoing complete resection of NSCLC. Patients received four courses of CDDP (40 mg/m2) and VNR (25 mg/m2) on days 1 and 8, every 3 weeks. There were 27 male and 13 female patients; the mean age was 65 years (range 38-78 years), the postoperative disease staging distribution was IIA/IIB/IIIA: 14/8/18 patients, and histological distribution was adenocarcinoma/squamous cell carcinoma/others: 24/12/4 patients, respectively. Of the 40 patients, 28 (70%) completed the four courses of treatment. The mean total dose administered was 279 mg/m2 CDDP (87.2%) and 172 mg/m2 VNR (86%). The major adverse events included Grade (G) 3 or higher neutropenia (80%), G3 phlebitis (5%) and vomiting (2.5%). There was no G2 or higher serum creatinine level elevation, G3 or higher anorexia and nausea, or any treatment-related deaths. The overall completion rate of four courses was 70 and 62.5% for patients aged 70 years and older, whereas the overall percentage of patients that could complete three or more courses was 85 and 87.5% for patients aged 70 years and older. The relapse-free survival rate was 60% at 3 years and 57.5% at 5 years. Overall survival rate was 80% at 3 years and 60% at 5 years. The present study demonstrated the sufficient tolerability, safety and efficacy of combined CDDP + VNR adjuvant chemotherapy with split-dose administration of CDDP, with a low risk of gastrointestinal toxicities or nephrotoxicity.

Evaluation of clinical pharmacist interventions for adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy.

Due to the increasing complexity of cancer chemotherapy and its associated supportive care, the role of clinical pharmacists in cancer chemotherapy is becoming increasingly more important. The present study evaluated the clinical interventions of a single pharmacist on the adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy. A single-center, retrospective study was conducted at the 614-bed, tertiary care Gifu University Hospital. Hospitalized patients with thoracic cancer who received cancer chemotherapy in the respiratory medicine ward between April 2013 and May 2014 were enrolled. One of the two clinical pharmacists in charge was based in the respiratory medicine ward and implemented pharmaceutical care for the patients, including management of adverse events. Patient data were recorded in the electronic medical chart and retrospectively analyzed. A total of 445 patients with thoracic cancer received cancer chemotherapy in the respiratory medicine ward. A total of 152 interventions (101 patients) were performed by the clinical pharmacist prior to the administration of cancer chemotherapy, half of which comprised the addition of drugs to prevent adverse events. A total of 190 patients (39.4%) experienced grade ≥2 non-hematological or grade ≥3 hematological adverse events associated with cancer chemotherapy, and 223 medical interventions for relief of adverse events lowered the incidence of grade ≥2 non-hematological or grade ≥3 hematological adverse events to 17.8%. Of these, 45.3 and 7.5% of medical interventions for non-hematological and hematological adverse events, respectively, were implemented based on the pharmacist's recommendations. These findings revealed the marked contribution of a single clinical pharmacist in the respiratory medicine ward to the prevention and relief of adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy.

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial.

BACKGROUND: Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies. MATERIALS AND METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours). RESULTS: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. CONCLUSION: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267. IMPLICATIONS FOR PRACTICE: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.

Clinical trial protocol of doublet therapy and olanzapine for carboplatin-induced nausea and vomiting in patients with thoracic cancer: a multicentre phase II trial.

INTRODUCTION: Adding neurokinin-1 receptor antagonist (NK1RA) to 5-hydroxytryptamine-3 receptor antagonist and dexamethasone (DEX) improved carboplatin (CBDCA)-induced chemotherapy-induced nausea and vomiting (CINV) in patients with thoracic cancer. NK1RAs with high-drug cost are raising medical expenses. Olanzapine (OLZ) is less expensive and can be expected to have an excellent effect on CINV. This phase II trial aimed at evaluating the efficacy and safety of 5 mg OLZ plus granisetron (GRN) and DEX in CBDCA combination therapy with area under curve (AUC) ≥5 mg/mL/min for the prevention of nausea and vomiting in patients with thoracic cancer. METHODS AND ANALYSIS: This is an open-label, single-arm, multicentre, phase II trial. Patients who receive CBDCA-based therapies (AUC ≥5) and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive a combination of GRN, DEX and OLZ. The primary endpoint is complete response (CR) rate, defined as the absence of emetic episodes and no use of rescue medication for 120 hours after the initiation of CBDCA. Forty-eight patients are required based on our hypothesis that this regimen can improve CR rate from 65% (null hypothesis) to 80% (alternative hypothesis) with a one-sided type I error of 0.1 and a power of 0.8. We set the target sample size at 50 considering dropouts. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000031267.

Immune thrombocytopenia induced by nivolumab in a patient with non-small cell lung cancer.

Antibodies targeting the receptor programmed death 1 on T cells have been approved for the treatment of lung cancer. Immune checkpoint inhibitors (ICIs) induce various immune-related adverse events. Life-threatening hematotoxicity can be provoked by ICI therapy. Although ICI-related endocrinopathy and interstitial lung disease have been well documented, hematotoxicity requiring intensive treatment is relatively rare. We describe a case of nivolumab induced thrombocytopenia after transient mild fever. A 77-year-old man with non-small cell lung cancer was administered nivolumab (240 mg/body, every 2 weeks) as second line therapy. On the day 2 after the first nivolumab infusion, he had a fever and his C-reactive protein level was elevated. Thoracic computed tomography revealed no interstitial lung disease or pneumonia. The fever resolved on day 9 and was not seen thereafter. On day 15 after the first nivolumab infusion, severe thrombocytopenia suddenly emerged. A bone marrow examination revealed no dysplasia or invasion. Based on the presence of high platelet-associated IgG titer, normal bone marrow plasticity and a lack of effectiveness of platelet infusion, we diagnosed nivolumab-induced immune thrombocytopenia. Daily administration of 60 mg of prednisolone restored the patient's platelet count and platelet-associated IgG. We also found that there was significant shrinkage of the primary lesion and that stable disease was achieved. One must be aware of this relatively rare side effect and the unusual clinical findings that could be associated with immunoreaction.

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases.

BACKGROUND/AIM: Nivolumab is an immune checkpoint inhibitor for advanced non-small cell lung cancer (NSCLC). We investigated the safety and efficacy of nivolumab by analyzing the response factor, adverse effects (AE), and the post-treatment condition of pretreated advanced or recurrent NSCLC patients. PATIENTS AND METHODS: Nivolumab (3 mg/kg) was administered to 79 pre-treated NSCLC patients from December 2015 to January 2018. Nivolumab efficacy and AE were assessed using the Response Evaluation Criteria in Solid Tumors and the Common Terminology Criteria, respectively. RESULTS: Progression-free survival (PFS) was significantly prolonged in cases where the therapeutic effect of the pretreatment was a partial response (p=0.0004). Five cases (6.3%) experienced grade 3-4 AEs. PFS was significantly prolonged in the skin rash group versus the non-skin rash group, and in patients where nivolumab treatment was discontinued. CONCLUSIONS: Long-term survival was observed in patients with skin rash. Therapeutic effect of nivolumab immediately following its administration appears to be favorable for survival.

Early-stage Clinical Characterization of Malignant Pleural Mesothelioma.

BACKGROUND/AIM: A strategy for improving survival of malignant pleural mesothelioma (MPM) patients is earlier diagnosis paired with earlier stage implementation of therapeutic interventions. This study aimed to determine the clinical signs of early-stage MPM to aid an earlier diagnosis and earlier-stage intervention. MATERIALS AND METHODS: Out of the 72 cases in our institution, 40 cases with 18F-FDG-PET/CT-negative MPM were retrospectively identified between 2007 and 2015. Overall survival rates were determined and compared with pathological features, histology, and treatment. RESULTS: The biphasic histological type of early-stage MPM was characterized by poor prognosis (p=0.0006). Additionally, the cytology-negative group (Class III and below) showed significantly shorter survival times (p=0.0290). There was no significant difference in survival between patients who received pleurectomy and those who received chemotherapy only (p=0.6991). Bimodal therapy resulted in a longer survival rate than trimodal therapy. CONCLUSION: In early-stage PET-negative MPM cases, biphasic histology and pleural effusion of Class III and below correlated with a poor prognosis. Surgical treatment using pleurectomy/decortication resulted in higher patient survival outcomes than therapy with extrapleural pneumonectomy.

Double cancer comprising malignant pleural mesothelioma and squamous cell carcinoma of the lung treated with radiotherapy: A case report.

Pleurectomy/decortication (P/D) is the surgical treatment of choice for early malignant mesothelioma, but it remains unclear whether radiotherapy along with P/D should be used as multimodal treatment for this disease. We herein present the case of a 76-year-old man with a history of asbestos exposure who was diagnosed with left-sided malignant pleural mesothelioma in February 2010. The patient underwent chemotherapy with a combination of cisplatin and pemetrexed and achieved stable disease, after which time he was kept under observation. A positron emission tomography/computed tomography scan performed in February 2011 revealed nodular shadows with fluorodeoxyglucose uptake in S3 of the left lung; using bronchoscopy, the patient was diagnosed with stage IIB (cT3N0M0) primary squamous cell carcinoma. Chemoradiotherapy with vinorelbine and 60 Gy/20 fr radiotherapy was performed, and a partial response was obtained, suggesting that the radiotherapy used to treat the carcinoma of the lung may have also helped control the disease activity of the pre-existing mesothelioma. The present case indicates the value of radiotherapy in the treatment of malignant mesothelioma. The aim of the present study was to examine the possibility of new multimodal treatments for mesothelioma, along with a discussion of the relevant literature.

Efficacy of Single-dose First-generation 5-HT3 Receptor Antagonist and Dexamethasone for Preventing Nausea and Vomiting Induced by Low-dose Carboplatin-based Chemotherapy.

BACKGROUND: Carboplatin (CBDCA) is known to exhibit a high emetic risk among moderate-emetic risk anticancer drugs, and the dose of CBDCA varies in different therapies. In concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC), the weekly administration of CBDCA (area under the curve (AUC) 2 mg/ml/min) and paclitaxel (PTX: 40 mg/m2) is frequently applied as standard therapy. However, the optimal antiemetic measures in the use of such low-dose CBDCA remain unclear. In this study, we retrospectively assessed the antiemetic effect of a single-dose of a first-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone in the weekly CBDCA+PTX therapy in CCRT. PATIENTS AND METHODS: The subjects were patients with NSCLC who were administered weekly CBDCA+PTX therapy in CCRT between January 2011 and December 2016 at our Department. As an antiemetic measure, a first-generation 5-HT3RA, azasetron (10 mg, orally) or granisetron (3 mg, intravenously), and dexamethasone (9.9 mg, intravenously) were administered on day 1. The patients were evaluated for the following efficacy end-points for the first cycle: Complete response (CR; defined as no vomiting or retching episodes with no rescue medication) in the acute phase (0-24 hours), delayed phase (>24-120 hours), and overall phase (0-120 hours). Other efficacy endpoints evaluated were no vomiting or retching, and no nausea in all phases. RESULTS: The subjects we assessed in this study were 46 patients who were administered weekly CBDCA+PTX therapy in CCRT. For the overall, acute, and delayed phases, the complete response rates were 89.1%, 100%, and 89.1%, respectively. The rate of no nausea in the overall, acute, and delayed phases was 78.3%, 100%, and 78.3%, respectively. The rate of no vomiting in the overall, acute, and delayed phases was 95.7%, 100%, and 95.7%, respectively. CONCLUSION: A single dose of a first-generation 5-HT3RA and dexamethasone had a favorable suppressive effect on nausea and vomiting in weekly CBDCA+PTX therapy for NSCLC.

Metabolic response assessment with 18F-FDG-PET/CT is superior to modified RECIST for the evaluation of response to platinum-based doublet chemotherapy in malignant pleural mesothelioma.

PURPOSE: Efficient monitoring of tumor responsiveness to chemotherapy is essential to mitigate high mortality risks and cytotoxic effects of chemotherapeutics. However, there is no consensus on the most suitable diagnostic technique/parameters for assessing response to chemotherapy in malignant pleural mesothelioma (MPM). We compared the tumor responsiveness of MPM patients as assessed using modified RECIST (mRECIST) criteria and integrated 18F-FDG-PET/CT. METHODS: Histologically confirmed MPM patients (N=82) who were treated with three cycles of cisplatin and pemetrexed, or carboplatin and pemetrexed, were included. mRECIST and integrated 18F-FDG-PET/CT were used to evaluate MPM tumor response to chemotherapy. Metabolic non-responders were defined as those with a 25% or greater increase in SUVmax compared with the previous value. Time to progression (TTP) and overall survival (OS) were compared between metabolic-responders and non-responders. RESULTS: After three cycles of chemotherapy, 62(75.6%) of the patients were classified as having SD, 15 (18%) with partial remission (PR), and 5 (6%) with progressive disease (PD), based on mRECIST criteria. The cumulative median OS was 728.0days (95% confidence interval [CI]: 545.9-910.1) and cumulative median TTP was 365.0days (95% CI: 296.9-433.1). For the 82 patients, the disease control rate was 93.9%, whereas the metabolic response rate was only 71.9% (p<0.001). All PD and PR patients were found to be metabolic responders on 18F-FDG-PET/CT; however, among the 62mRECIST SD patients, 18 (29%) were classified as metabolic non-responders. The median TTP for metabolic responders was 13.7 months, while it was 10.0 months for non-responders(p<0.001). Metabolic responders had a trend toward longer OS, although the difference did not reach statistical significance (metabolic responders:33.9 months; non-responders: 21.6 months; p>0.05). CONCLUSION: Several mRECIST-confirmed SD MPM patients may be classified as metabolic non-responders on18F-FDGPET/CT. Metabolic response is significantly correlated with the median TTP, suggesting it should be included in the evaluation of the response to chemotherapy in MPM patients classified as mRECIST SD, to identify non-responders.

Chemotherapy for advanced non-small cell lung cancer with a focus on squamous cell carcinoma.

Lung cancers are broadly divided into small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and the treatments for each differ. NSCLC includes squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and others. However, because there is little difference in treatment efficacy between these histological types, they have collectively been treated as a single entity. Cytotoxic anti-cancer agents, mainly platinum-based drugs, are the first-line treatment for unresectable advanced NSCLC, and the standard therapy is combination chemotherapy with two drugs, usually involving one platinum-based and one unrelated cytotoxic drug. Such regimens have been used for all the different histological types. In recent years, however, genetic abnormalities in NSCLCs known as driver mutations have been identified. These include epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, which are responsible for both carcinogenesis and cancer growth and survival. The advent of molecular targeted therapies that target these mutations has clearly improved the prognosis for NSCLC. However, effective molecular targeted drugs or novel anti-cancer agents that greatly prolong survival have not yet been developed to treat squamous cell carcinoma or 30% of adenocarcinomas. For patients with these types of cancers, it is important to use existing cytotoxic anti-cancer agents appropriately in their treatment. In this paper, we review the treatment options for unresectable advanced NSCLC on the basis of recent findings, with a particular focus on squamous cell carcinoma, for which groundbreaking drugs have yet to be discovered.

Noninvasive Tissue Characterization of Lung Tumors Using Integrated Backscatter Intravascular Ultrasound: An Ex Vivo Comparative Study With Pathological Diagnosis.

BACKGROUND: Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses. METHODS: Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson's trichrome staining were determined by using an imaging processor. RESULTS: The IBS values in tumor tissue were significantly lower than those in normal lung tissue (-50.9 ± 2.6 dB and -47.6 ± 2.6 dB, respectively; P < .001). The IBS values of adenocarcinomas associated with a good 5-year survival rate were higher than those of non-adenocarcinomas (-48.1 ± 1.6 dB and -52.6 ± 1.4 dB; P < .001). There were significant correlations between the IBS values and the relative interstitial area or micro air area in tumor (r = 0.53 and r = 0.67; P < .01). After combining normal lung tissue and adenocarcinomas with a good prognosis, the sensitivity and specificity for establishing the presence of lung tumors were 84% and 85%. CONCLUSIONS: Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique.

Pharmacokinetics of consecutive oral moxifloxacin (400 mg/day) in patients with respiratory tract infection.

A population pharmacokinetic analysis was performed to investigate the pharmacokinetics of moxifloxacin (400 mg) following a once-daily oral administration in 28 patients with respiratory tract infection disease. The maximum plasma concentration and the area under the plasma concentration-time curve were 3.97 µg/ml and 51.74 µg·h/ml, respectively; these values were nearly equivalent to those of healthy adult men. Two adverse drug reactions (nausea, vomiting) occurred, but both reactions were mild and nonserious and the patients recovered without treatment. The pharmacokinetic profile of moxifloxacin in Japanese patients with respiratory tract infection and an underlying disease should thus be considered safe and comparable with that in healthy adult men, and adjustment of dose may do not need for age, sex, body weight, or renal function.

Prevention of radiation esophagitis by polaprezinc (zinc L-carnosine) in patients with non-small cell lung cancer who received chemoradiotherapy.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) plays an important role in multimodality therapy for non-small cell lung cancer. However, esophagitis often develops as a complication of CCRT, causing treatment delays and reducing the patient's quality of life. We examined the efficacy of polaprezinc (PZ), zinc L-carnosine used for the therapy of gastric ulcer, against the onset of esophagitis caused by CCRT for lung cancer. PATIENTS AND METHODS: Patients who concurrently underwent chemotherapy with carboplatin and paclitaxel and thoracic radiotherapy at Gifu University Hospital during a period of January 2011 and May 2015 were the subjects of the present study. Patients received a mixture of sodium alginate solution and aluminum-magnesium hydroxide gel with (PZ group) or without (control group) PZ for prevention of radiation esophagitis. RESULTS: PZ significantly inhibited the development of grade ≥2 radiation esophagitis (HR 0.397, 95% confidence interval, 0.160-0.990; P=0.047). In addition, PZ lowered the incidence of grade ≥2 esophagitis at the time point of 40 Gy irradiation (26.3% versus 63.2%, P=0.05). However, there were no significant differences in the incident rates of other adverse events associated with chemoradiotherapy between the PZ group and control group. Moreover, PZ had no significant influence on the tumor response rate. CONCLUSION: PZ significantly retarded the development as well as the incidence of grade ≥2 esophagitis without affecting the tumor response.

Suppression of heme oxygenase-1 activity reduces airway hyperresponsiveness and inflammation in a mouse model of asthma.

OBJECTIVE: Carbon monoxide (CO) levels in expired gas are higher in patients with bronchial asthma than in healthy individuals. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that catalyzes the degradation of heme to yield biliverdin, CO and free iron. Thus, HO-1 is implicated in the pathogenesis of bronchial asthma. However, whether HO-1 expression and activity in lung tissue are related to allergic airway inflammation remains unclear. We investigated whether expression of HO-1 is related to allergic airway inflammation in lungs and whether HO-1 could influence airway hyperresponsiveness and eosinophilia in mice sensitized to ovalbumin (OVA). METHODS: C57BL/6 mice immunized with OVA were challenged thrice with an aerosol of OVA every second day for 8 days. HO-1-positive cells were identified by immunostaining in lung tissue, and zinc protoporphyrin (Zn-PP), a competitive inhibitor of HO-1, was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 23 (day before inhalation of OVA) and immediately before inhalation on the subsequent 4 days (total five doses). Mice were analyzed for effects of HO-1 on AHR, inflammatory cell infiltration and cytokine levels in lung tissue. Ethical approval was obtained from the concerned institutional review board. RESULTS: Number of HO-1-positive cells increased in the subepithelium of the bronchi after OVA challenge, and HO-1 localized to alveolar macrophages. Zn-PP clearly inhibited AHR, pulmonary eosinophilia and IL-5 and IL-13 expression in the lung tissue. CONCLUSION: Expression of HO-1 is induced in lung tissue during attacks of allergic bronchial asthma, and its activity likely amplifies and prolongs allergic airway inflammation.

[Analysis of Pemetrexed Monotherapy in Advanced Non-Small Cell Lung Cancer Patients with Impaired Renal Function].

Toxicity and efficacy of pemetrexed monotherapy in advanced non-small-cell lung cancer patients with impaired renal function treated between May 2009 and May 2012 at Gifu University Hospital were retrospectively analyzed. A total of 10 and 17 patients had a creatinine clearance rate (Ccr) of <45 mL/min and ≥45 mL/min, respectively. The median age was higher in the Ccr<45 mL/min group (78.9 years) than in the ≥45 mL/min group (65.2 years). The rate of neutropenia above Grade 3 was 30% in the Ccr<45 mL/min group and 6% in the ≥45 mL/min group. Therefore, reducing the dose of pemetrexed should be considered in patients with impaired renal function. Non-hematologic toxicities were not correlated with the renal function. There was no treatment-related death, and most of the toxicities were mild and tolerable. Stable disease was observed in 6 patients (60%) in the Ccr<45 mL/min group, and in 12 patients (70%) in the Ccr≥45 mL/min group, although some patients in both groups showed neither complete nor partial responses. The disease control rate and median progression-free survival time were 60% and 2.8 months in the Ccr<45 mL/min group, and 70% and 2.9 months in the Ccr≥45 mL/min group, respectively. Thus, in this analysis, treatment with pemetrexed resulted in clinically equivalent efficacy in advanced non-small-cell lung cancer patients regardless of the state of renal function.

Paraneoplastic neurological syndrome in a patient with squamous cell lung cancer.

A 78-year-old man presented with urinary retention and difficulty walking. Both legs showed muscle weakness, and he was experiencing lower body hypoesthesia. T2-weighted magnetic resonance imaging revealed lesions with high signal intensity and enhancement in the spinal cord and cerebrum. A cerebrospinal fluid specimen showed inflammatory changes, but negative cytology findings. Chest computed tomography revealed a tumor measuring 40 mm in diameter, and a lung biopsy revealed the presence of squamous cell carcinoma. We diagnosed the patient with paraneoplastic neurological syndrome related to lung cancer. The patient was treated with steroid pulse therapy and chemotherapy, which relieved the symptoms and enabled the patient to achieve an independent gait.

A randomized controlled non-inferiority study comparing the antiemetic effect between intravenous granisetron and oral azasetron based on estimated 5-HT3 receptor occupancy.

BACKGROUND: The acute antiemetic effect was compared between oral azasetron and intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor occupancy theory. PATIENTS AND METHODS: Receptor occupancy was estimated from reported data on plasma concentrations and affinity constants to 5-HT(3) receptor. A randomized non-inferiority study comparing acute antiemetic effects between oral azasetron and intravenous granisetron was performed in 105 patients receiving the first course of carboplatin-based chemotherapy for lung cancer. RESULTS: Azasetron exhibited the highest 5-HT(3) receptor occupancy among various first-generation 5-HT(3) antagonists. The complete response to oral azasetron was shown to be non-inferior to that of intravenous granisetron, in which the risk difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit of the confidence intervals did not exceed the negative non-inferiority margin (-0.1). The complete response during the overall period was not different (68% versus 67%). CONCLUSION: Oral azasetron was found to be non-inferior to intravenous granisetron in the acute antiemetic effect against moderately emetogenic chemotherapy.