Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

Effects of adding a neurokinin-1 receptor antagonist to 5 mg olanzapine, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for preventing carboplatin-induced nausea and vomiting: a propensity score-matched analysis.

BACKGROUND: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK1RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK1RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy. METHODS: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK1RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK1RA (non-NK1RA group: 31 patients) and with NK1RA (NK1RA group: 31 patients). The patients were selected using propensity score matching. RESULTS: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK1RA group and 96.8% in the NK1RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine. CONCLUSIONS: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT3RA, and DEX without NK1RA may be a treatment option for patients receiving carboplatin-based 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.

Efficacy and safety of 5 mg olanzapine for nausea and vomiting management in cancer patients receiving carboplatin: integrated study of three prospective multicenter phase II trials.

BACKGROUND: The efficacy of olanzapine as an antiemetic agent in cancer chemotherapy has been demonstrated. However, few high-quality reports are available on the evaluation of olanzapine's efficacy and safety at a low dose of 5 mg among patients treated with carboplatin regimens. Therefore, in this study, we investigated the efficacy and safety of 5 mg olanzapine for managing nausea and vomiting in cancer patients receiving carboplatin regimens and identified patient-related risk factors for carboplatin regimen-induced nausea and vomiting treated with 5 mg olanzapine. METHODS: Data were pooled for 140 patients from three multicenter, prospective, single-arm, open-label phase II studies evaluating the efficacy and safety of olanzapine for managing nausea and vomiting induced by carboplatin-based chemotherapy. Multivariable logistic regression analyses were performed to determine the patient-related risk factors. RESULTS: Regarding the endpoints of carboplatin regimen-induced nausea and vomiting control, the complete response, complete control, and total control rates during the overall study period were 87.9, 86.4, and 72.9%, respectively. No treatment-related adverse events of grade 3 or higher were observed. The multivariable logistic regression models revealed that only younger age was significantly associated with an increased risk of non-total control. Surprisingly, there was no significant difference in CINV control between the patients treated with or without neurokinin-1 receptor antagonist. CONCLUSIONS: The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy.

Evaluation of covalent binding of flutamide and its risk assessment using 19F-NMR.

The formation of reactive metabolites (RMs) is a problem in drug development that sometimes results in severe hepatotoxicity. As detecting RMs themselves is difficult, a covalent binding assay using expensive radiolabelled tracers is usually performed for candidate selection. This study aimed to provide a practical approach toward the risk assessment of hepatotoxicity induced by covalent binding before candidate selection. We focused on flutamide because it contains a trifluoromethyl group that shows a strong singlet peak by 19F nuclear magnetic resonance (NMR) spectrometry. The covalent binding of flutamide was evaluated using quantitative NMR and its risk for hepatotoxicity was assessed by estimating the RM burden, an index that reflects the body burden associated with RM exposure by determining the extent of covalent binding, clinical dose and in vivo clearance. The extent of covalent binding and RM burden was 296 pmol/mg/h and 37.9 mg/day, respectively. Flutamide was categorised as high risk with an RM burden >10 mg/day consistent with its clinical hepatotoxicity. These results indicate that a combination of covalent binding assay using 19F-NMR and RM burden is useful for the risk assessment of RMs without using radiolabelled compounds.

Simultaneous and rapid determination of gefitinib, erlotinib and afatinib plasma levels using liquid chromatography/tandem mass spectrometry in patients with non-small-cell lung cancer.

A simultaneous, selective, sensitive and rapid liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of gefitinib, erlotinib and afatinib in 250 µL samples of human blood plasma. Diluted plasma samples were extracted using a liquid-phase extraction procedure with tert-butyl methyl ether. The three drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2 mL/min for 5 min. The drugs were detected using a tandem mass spectrometer with electrospray ionization using imatinib as an internal standard. Calibration curves were generated over the linear concentration range of 0.05-100 nm in plasma with a lower limit of quantification of 0.01 or 0.05 nm for all compounds. Finally, the validated method was applied to a clinical pharmacokinetic study in patients with nonsmall-cell lung cancer (NSCLC) following the oral administration of afatinib. These results indicate that this method is suitable for assessing the risks and benefits of chemotherapy in patients with NSCLC and is useful for therapeutic drug monitoring for NSCLC treatment. As far as we know, this is the first report on LC-MS/MS method for the simultaneous quantification of NSCLC tyrosine kinase inhibitor plasma concentrations including afatinib. Copyright © 2015 John Wiley & Sons, Ltd.

[Relationship between Coronary Plaque Stability Evaluated by Intravascular Ultrasound and Laboratory Parameters].

Tissue characteristics of coronary plaque have been reported to be associated with cardiovascular events. The stabilization of vulnerable tissue components such as the lipid pool rather than regression of the plaque volume is considered to be of major benefit in the reduction of cardiovascular events. Conventional echocardiography, especially intravascular ultrasound imaging (IVUS), is widely used to determine calcification and the three layers of the arterial wall. However, differentiation of the lipid pool from fibrous tissue using the echo intensity is difficult. Recently, an integrated backscatter (IB) ultrasound technique was developed. The ultrasound IB power ratio is a function of the difference in acoustic characteristic impedance between the medium and target tissue, and the acoustic characteristic impedance is determined by the density of tissue multiplied by the speed of sound. For more comprehensive plaque analysis using IB-IVUS, three-dimensional IB-IVUS offers the potential for the quantitative volumetric tissue characterization of coronary atherosclerosis. Several large clinical trials demonstrated that lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduces cardiovascular events. The IB techniques provide useful clinical information on the effects of statins and other medications. The presence of lipid-rich plaque is associated with the incidence of atherosclerotic diseases; therefore, ultrasound IB techniques are useful to detect coronary atherosclerotic lesions.

[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.

Relationship Between Osimertinib Concentration and Clinical Response in Japanese Patients With Non-small Cell Lung Cancer.

BACKGROUND/AIM: Osimertinib is the first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The present study aimed to determine the previously unclarified association of osimertinib plasma trough concentrations with efficacy, adverse events, and genetic polymorphisms in Japanese patients with NSCLC harboring EGFR mutations. PATIENTS AND METHODS: In this prospective study, blood samples of 25 patients who received osimertinib were collected to measure plasma osimertinib concentrations and to genotypically characterize ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2 polymorphisms. Plasma osimertinib concentrations were analyzed using validated multiple reaction monitoring mode-based liquid chromatography-tandem mass spectrometry. Osimertinib concentration necessary to achieve optimal median progression-free survival (PFS) was determined using receiver operating characteristic curve analysis. PFS and overall survival were analyzed using the Kaplan-Meier method, and between-group differences were compared using the log-rank test. Plasma osimertinib concentrations between different patient groups were compared using the Mann-Whitney U-test. RESULTS: Patients were divided into high and low concentration groups based on a plasma osimertinib cut-off concentration of 211 ng/ml. Median PFS was longer in the high trough concentration group than that in the low trough concentration group (46.3 vs. 16.8 months, p=0.029). Plasma osimertinib concentrations adjusted for dose and body weight did not differ between the patients with and without variant polymorphisms. CONCLUSION: Monitoring plasma trough concentrations during maintenance might improve osimertinib treatment efficacy in patients with NSCLC harboring EGFR mutations.

Effect of Mirtazapine for the Prevention of Nausea and Vomiting in Patients With Thoracic Cancer Receiving Platinum-based Chemotherapy.

BACKGROUND/AIM: Mirtazapine, which exerts an antagonistic effect on 5-hydroxytryptamine type 5-HT2A, 5-HT2C, 5-HT3 and H1 receptors, is considered useful for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). This study investigated the efficacy and safety of mirtazapine for the prevention of CINV in patients with thoracic cancer receiving platinum-based chemotherapy. PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with thoracic cancer receiving platinum-based chemotherapy with 15 mg mirtazapine once daily as a prophylactic antiemetic drug between January 2014 and December 2021. The effects of mirtazapine added to the standard antiemetic regimen for the prevention of CINV were evaluated in patients who had poor control of CINV in a preceding cycle and in patients who received the standard antiemetic therapy plus mirtazapine from their first cycle. RESULTS: A total of 35 patients were evaluated. Of these, 14 had poor control of CINV in a preceding cycle and received the standard antiemetic therapy plus mirtazapine in the next cycle. The rate of complete response in the delayed period in these patients was significantly improved from the preceding cycle to the next cycle (35.7% vs. 85.7%, p=0.018). In contrast, the other 21 patients had received the standard antiemetic regimen plus mirtazapine from the first cycle. The rate of complete response in the delayed period in these patients receiving the triplet antiemetic regimen plus mirtazapine as part of a cisplatin-based or carboplatin-based regimen and in patients receiving a doublet antiemetic regimen plus mirtazapine in a carboplatin-based regimen was 100%, 85.7% and 100%, respectively. No severe adverse events, including somnolence, were observed with the addition of mirtazapine. CONCLUSION: The addition of mirtazapine to the standard antiemetic regimen for CINV may be beneficial with acceptable safety when administered in association with platinum-based regimens to patients with thoracic cancer.

Prognostic Model of Baseline Medications plus Neutrophil-to-lymphocyte Ratio in Patients with Advanced Non-small-cell Lung Cancer Receiving Immune Checkpoint Inhibitor plus Platinum Doublet: A Multicenter Retrospective Study.

Background: Association between baseline medications plus neutrophil-to-lymphocyte ratio (NLR) and the effectiveness of immune checkpoint inhibitor (ICI) plus platinum doublet remains unknown, despite several reported prognostic models. We used real-world data to investigate whether baseline medications plus NLR predict survival outcomes in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICI plus platinum doublet. Methods: This multicenter, retrospective, observational study conducted in Japan between December 2018 and March 2021 used real-world data of consecutive patients with advanced NSCLC who received ICI (pembrolizumab or atezolizumab) plus platinum doublet as first-line treatment. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The prognostic score for baseline medications plus NLR was weighted by regression ß coefficients and used to categorize patients into good, intermediate, and poor prognoses groups. In addition, time-dependent receiver operating characteristic curve analyses and univariable and multivariable Cox proportional hazards models were constructed. Results: Overall, 241 patients were included. Poor prognosis was significantly associated with worse PFS (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.08-2.94; P = 0.025) and OS (HR: 3.59; 95% CI: 2.05-6.28; P < 0.001) than good prognosis. Harrell's C-index for this prognostic model was 0.648. Conclusions: Baseline medication plus NLR could predict progressively worse survival outcomes in patients with advanced NSCLC receiving ICI plus platinum doublet and could be used as a prognostic index for poor outcomes.

Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of oxidative stress in rabbits.

Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

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.

Cancer cachexia as a determinant of efficacy of first-line pembrolizumab in patients with advanced non-small cell lung cancer.

Pembrolizumab, either as a type of monotherapy or in combination with cytotoxic anticancer agents, is effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the development of cancer cachexia may adversely affect anticancer drug therapy. The present study investigated the effect of cancer cachexia on clinical outcomes in patients with advanced NSCLC who received first-line pembrolizumab. The data of patients with advanced NSCLC receiving first-line monotherapy or combination therapy with pembrolizumab were retrospectively analyzed. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). Clinical outcome was compared between patients with and without cancer cachexia. A total of 53 patients were analyzed. Among all patients, median TTF and OS were significantly shorter in patients with cancer cachexia than in those without [TTF: 5.8 vs. 10 months; hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.07-4.24; P=0.016; OS: 12.1 months vs. not reached; HR: 5.85; 95% CI: 2.0-17.1; P=0.001]. In addition, TTF in the pembrolizumab monotherapy group was significantly shorter in patients with cancer cachexia than in those without, but no significant difference was detected in patients receiving pembrolizumab combination therapy. The incidence of AEs did not significantly differ between patients with and without cancer cachexia, except with regard to hypothyroidism. In conclusion, although cancer cachexia is prognostic of a poor outcome in patients with advanced NSCLC who receive first-line pembrolizumab, cancer cachexia might not affect therapeutic efficacy in combination therapy with pembrolizumab and cytotoxic anticancer agents.

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.

COVID-19 and acute exacerbation of interstitial lung disease.

We conducted a study to examine the effect of COVID-19 on the acute exacerbation of interstitial lung disease (AE-ILD) early in the COVID-19 epidemic (January 1-April 30, 2020). An online questionnaire survey was conducted, which was completed by 134 hospitals. During this period, 854 patients with AE-ILD (including 12 cases of COVID-AE-idiopathic pulmonary fibrosis were hospitalized at 128 hospitals. In comparison, the total number of AE-ILD hospitalizations during the same period in 2019 was 894. The number of hospitalizations increased at 17 hospitals, decreased at 27, and remained the same at 88 hospitals in 2020 compared to the same period in 2019. In 2020, COVID-19-related acute exacerbations had a significantly worse prognosis than non-COVID-19-related acute exacerbations in both 30-day and 90-day mortality. Because the prognosis of AE-ILD associated with COVID-19 is extremely poor, prevention of COVID-19 is especially important for patients with ILD.

Primary Prophylaxis of Febrile Neutropenia With Pegfilgrastim in Small-cell Lung Cancer Patients Receiving Amrubicin as Second-line Therapy.

BACKGROUND/AIM: We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin (AMR). PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with SCLC receiving AMR as second-line therapy. RESULTS: A total of 33 patients were treated with AMR (no PEG group), while 13 patients were treated with AMR plus prophylactic administration of PEG (PEG group). The severity of neutropenia was significantly reduced in the PEG group compared to the no PEG group (p=0.02). The incidence of FN in the no PEG and PEG groups was 27.3% and 7.7%, respectively. The time to development of FN tended to be longer in the PEG group compared to the no PEG group (p=0.132). CONCLUSION: Primary prophylaxis with PEG may be beneficial in reducing the risk of FN in patients with SCLC receiving AMR.

Massive hematuria from the bilateral upper urinary tract in a patient treated for advanced lung cancer with gefitinib.

We report a case of gefitinib-induced bilateral upper urinary tract bleeding in an 82-year-old woman administered the drug daily for advanced non-small cell adenocarcinoma of the lung (T4N3M0). Hematuria is an uncommon adverse effect of gefitinib, and in most cases, the bleeding site is unknown. On the 44th day of oral gefitinib administration, the patient noted asymptomatic macroscopic bloody urine. Cystoscopy revealed bleeding from the bilateral ureteric orifices without hemorrhagic inflammation of the bladder. One week later, she was admitted complaining of severe abdominal pain, and her condition was found to be complicated by liver damage and renal dysfunction. We stopped gefitinib administration and started hydration and diuresis. Renal function and urine output soon recovered, and at the request of the patient, we restarted gefitinib, administering it every other day, which was sufficient to maintain antitumor activity and stabilize the disease. On the 41st day after restarting gefitinib, hematuria and proteinuria reappeared. We therefore stopped the gefitinib, and the patient was followed with supportive care. The patient's autopsy findings denied organic urologic diseases. Instead, the reproducibility of the hematuria from the upper urinary system strongly suggests an unexpected gefitinib-related adverse effect.

Polymerase chain reaction positivity of Pneumocystis jirovecii during primary lung cancer treatment.

OBJECTIVE: When treating lung cancer, pneumocystic pneumonia is a life-threatening complication seen during chemotherapy. Polymerase chain reaction is used to detect its cause, Pneumocystis jirovecii, but polymerase chain reaction positives without pneumocystic pneumonia are sometimes seen. The purpose of this study was to assess the frequency of pneumocystic pneumonia during cancer treatment. METHODS: Fifty induced sputum specimens and 4 bronchoalveolar lavage specimens collected from 50 patients with acute respiratory symptoms during anticancer therapy were retrospectively studied after classifying the patients into lung cancer (n = 29) and solid tumor (n = 21) groups. All of the patients in both groups had an interstitial shadow suspected of being pneumocystic pneumonia, and all had polymerase chain reaction tests. RESULTS: Eleven of the 54 specimens were polymerase chain reaction positive, and 1 patient was clinically diagnosed with pneumocystic pneumonia. The incidence of polymerase chain reaction positivity in the lung cancer group was significantly higher than in the solid tumor group (31 vs. 5%; P = 0.03), and the incidence of subclinical pneumocystic pneumonia (29 vs. 5%; P = 0.059) also tended to be higher in that group. There were no significant biochemical differences between the two groups, irrespective of the polymerase chain reaction results. Among polymerase chain reaction-positive patients in the lung cancer group, the cumulative dose of corticosteroid administration tended to be higher than among the polymerase chain reaction-negative patients (P = 0.09). Following the polymerase chain reaction tests, nearly all polymerase chain reaction-positive patients without pneumocystic pneumonia received antipneumocystic agents, and none developed pneumocystic pneumonia. CONCLUSIONS: Our findings suggest polymerase chain reaction positivity for P. jirovecii will be detected in a fraction of lung cancer patients. Although it is difficult to predict the need for administration of pneumocystic pneumonia treatment to subclinical pneumocystic pneumonia based on polymerase chain reaction and biochemical results, polymerase chain reaction-positive patients should be followed-up with antipneumocystic agents to ensure they are not at an early stage of pneumocystic pneumonia.

Use of multidetector row CT to evaluate the need for bronchial arterial embolization in hemoptysis patients.

BACKGROUND: Bronchial artery (BA) embolization (BAE) is recommended as a minimally invasive therapy for hemoptysis, though some patients recover after only conservative treatment. OBJECTIVES: The purpose of our study was to assess the characteristics of BAs using multidetector row computed tomography (MDCT) and identify BAs requiring BAE without BA angiography (BAG). METHODS: We retrospectively studied 41 patients and classified the visualized BAs into groups based on their BAE and bleeding statuses. Patients presenting with massive hemoptysis requiring emergency BAE were excluded. Patients presenting with persistent hemoptysis that was resistant to conservative treatment received BAE. Radiologists measured BA diameters at the ostium, bronchial bifurcation and pulmonary hilum, and also evaluated the degree of vascularization. RESULTS: MDCT enabled visualization of 102 ostia and 96 traceable BAs. Among the participating patients, 13 had at least one ectopic origin. We obtained a good correlation between BAG and MDCT diameters (r = 0.709, p < 0.001). The diameters of BAs responsible for bleeding and receiving BAE were apparently larger in each measured segment than those that were not (p < 0.05). Moreover, the diameters of arteries receiving BAE remained largely unchanged from the origin to the hilum and through the mediastinum. BAs with low MDCT scores were significantly less likely to required BAE than those with high scores (p = 0.004), and in multiple logistic regression analysis, ostium diameter and bleeding status were independent predictive factors for BAE. CONCLUSIONS: Evaluation of BAs on MDCT could be useful for identifying the anatomical characteristics of bleeding-related BAs and determining whether BAE is indicated or whether conservative treatment is sufficient.