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1.
Sci Rep ; 13(1): 19729, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37957228

ABSTRACT

Small amounts of epidermal growth factor receptor (EGFR) T790M mutation (micro-T790M), which is detected using droplet digital PCR (ddPCR) but not conventional PCR, in formalin-fixed and paraffin-embedded (FFPE) samples have been investigated as a predictive factor for the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). However, the predictive value of micro-T790M remains controversial, possibly owing to the failure to examine artificial T790M in FFPE specimens. Therefore, we examined the predictive value of micro-T790M in first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKI efficacy using a new method to exclude FFPE-derived artificial mutations in our retrospective cohort. The primary objective was time to treatment failure (TTF) of 1G, 2G, and 3G EGFR-TKIs according to micro-T790M status. In total, 315 patients with EGFR-positive non-small cell lung cancer treated with 1G, 2G, and 3G EGFR-TKIs were included in this study. The proportion of patients positive for micro-T790M in the 1G, 2G, and 3G EGFR-TKI groups was 48.2%, 47.1%, and 47.6%, respectively. In the micro-T790M-positive group, the TTF was significantly longer in the 2G and 3G EGFR-TKI groups than in the 1G TKI group. No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.


Subject(s)
Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Drug Resistance, Neoplasm , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Retrospective Studies , /therapeutic use
2.
Respir Investig ; 61(6): 746-754, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37714093

ABSTRACT

BACKGROUND: Few studies have been conducted on comprehensive genomic profiling (CGP) panels in Japanese patients with thoracic malignancies after completing standard treatment. Consequently, its value in clinical practice remains unclear. METHODS: We conducted a retrospective study of Japanese patients with thoracic malignancies who underwent CGP between June 2019 and November 2022 at our hospital. We evaluated the detection rate of actionable genetic alterations and percentage of patients who received genomically-matched therapy. Furthermore, we examined the value of the CGP panel in patients who underwent multiplex gene-panel testing prior to their initial treatment. This study was performed in accordance with the principles of the Declaration of Helsinki. RESULTS: The study included 56 patients, of whom 47 (83.9%) had actionable genetic alterations and 8 (14.3%) received genomically-matched therapy. Of these, four patients were treated with approved drugs and three patients were treated with investigational agents. In addition, one patient was treated with approved drugs using the patient-directed care system. Of the 17 patients who had multiplex gene-panel testing performed at the start of their initial therapy, two (11.8%) were newly identified by the CGP panel and subsequently received genomically-matched therapy. EGFR L718Q and MET amplification were observed in two of the seven patients with epidermal growth factor receptor-tyrosine kinase inhibitor resistance. CONCLUSIONS: The CGP panel could identify genetic alterations, thereby facilitating genomically-matched therapy, even in patients with thoracic malignancies who could not be identified using multiplex gene-panel testing.


Subject(s)
Lung Neoplasms , Thoracic Neoplasms , Humans , Retrospective Studies , East Asian People , Lung Neoplasms/pathology , Thoracic Neoplasms/genetics , Genomics
3.
Cancer Rep (Hoboken) ; 6(4): e1793, 2023 04.
Article in English | MEDLINE | ID: mdl-36727271

ABSTRACT

BACKGROUND: Pegfilgrastim is recommended in docetaxel plus ramucirumab (DTX + RAM) therapy for recurrent nonsmall cell lung cancer (NSCLC) because of the associated frequency of febrile neutropenia (FN). However, the FN occurs less frequently when the dose of DTX is reduced because of other adverse events, such as appetite loss and oral mucositis. METHODS AND RESULTS: Twenty-two patients with recurrent NSCLC who received DTX + RAM therapy at the Hiroshima Prefectural Hospital. The cut-off value which is the most unlikely to cause FN without the combined use of pegfilgrastim was set using a receiver operating characteristic (ROC) curve. This was created according to the dose of DTX and the presence or absence of the onset of FN. We compared the incidence of FN when a DTX dose above and below the cut-off value was used. The ROC curve showed that 48 mg/m2 was the best cut-off value that predicted whether FN was likely to occur when pegfilgrastim was not used concurrently. The incidence of FN was 26.1% for DTX ≥48 mg/m2 and 5.1% for DTX <48 mg/m2 . CONCLUSIONS: Pegfilgrastim can be discontinued when the dose of DTX is reduced to <48 mg/m2 due to nonhematological toxicities.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Docetaxel , Drug Tapering , Lung Neoplasms/drug therapy , Ramucirumab
4.
Int J Clin Oncol ; 28(1): 69-78, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36357710

ABSTRACT

BACKGROUND: Management of cancer-associated venous thromboembolism (VTE) is essential in cancer treatment selection and prognosis. However, currently, no method exists for assessing VTE risk associated with advanced lung cancer. Therefore, we assessed VTE risk, including driver gene mutation, in advanced lung cancer and performed a Khorana score validation. METHODS: The Rising-VTE/NEJ037 study was a multicenter prospective observational study that included patients with advanced lung cancer. In the Rising-VTE/NEJ037 study, the Khorana score was calculated for enrolled patients with available data on all Khorana score components. The modified Khorana score was based on the body mass index of ≥ 25 kg/m2, according to the Japanese obesity standard. A multivariate logistic regression analysis, including patient background characteristics, was performed to evaluate the presence of VTE 2 years after the lung cancer diagnosis. RESULTS: This study included 1008 patients with lung cancer, of whom 100 (9.9%) developed VTE. From the receiver operating characteristic curve analysis, VTE risk could not be determined because both the Khorana score (0.518) and modified Khorana score (0.516) showed very low areas under the curve. The risk factors for VTE in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2 and diastolic blood pressure. CONCLUSION: The Khorana score, which is widely used in cancer-VTE risk assessment, was less useful for Japanese patients with advanced lung cancer. Prothrombin fragment 1 + 2, a serum marker involved in coagulation, was more suitable for risk identification. CLINICAL TRIAL INFORMATION: jRCTs061180025.


Subject(s)
Lung Neoplasms , Venous Thromboembolism , Humans , Female , Venous Thromboembolism/genetics , Prospective Studies , Lung Neoplasms/complications , Lung Neoplasms/genetics , Risk Factors , Prognosis , Risk Assessment , Retrospective Studies
5.
Cancers (Basel) ; 14(24)2022 Dec 17.
Article in English | MEDLINE | ID: mdl-36551721

ABSTRACT

Introduction/Background: Chemoradiotherapy (CRT) followed by durvalumab, an immune checkpoint inhibitor, is the standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a life-threatening toxicity caused by these treatments; however, risk factors for the ILD have not yet been established. Interstitial lung abnormalities (ILAs) are computed tomography (CT) findings which manifest as minor interstitial shadows. We aimed to investigate whether ILAs could be risk factors for grade-two or higher ILD during durvalumab therapy. Patients and Methods: Patients with NSCLC who received durvalumab after CRT from July 2018 to June 2021 were retrospectively enrolled. We obtained patient characteristics, laboratory data, radiotherapeutic parameters, and chest CT findings before durvalumab therapy. Results: A total of 148 patients were enrolled. The prevalence of ILAs before durvalumab treatment was 37.8%. Among 148 patients, 63.5% developed ILD during durvalumab therapy. The proportion of patients with grade-two or higher ILD was 33.8%. The univariate logistic regression analysis revealed that older age, high dose-volume histogram parameters, and the presence of ILAs were significant risk factors for grade-two or higher ILD. The multivariate analysis showed that ILAs were independent risk factors for grade-two or higher ILD (odds ratio, 3.70; 95% confidence interval, 1.69−7.72; p < 0.001). Conclusions: We showed that pre-existing ILAs are risk factors for ILD during durvalumab treatment after CRT. We should pay attention to the development of grade-two or higher ILD during durvalumab treatment in patients with ILAs.

6.
Ther Adv Med Oncol ; 14: 17588359221110171, 2022.
Article in English | MEDLINE | ID: mdl-35898966

ABSTRACT

Background: Venous thromboembolism (VTE) is a well-known type of cancer-associated thrombosis and a common complication of malignancy. However, the incidence of VTE associated with lung cancer and the effectiveness of direct oral anticoagulants remain unclear. This study aimed to identify the incidence of VTE associated with lung cancer at the time of diagnosis or during treatment, the efficacy and safety of edoxaban, and associated risk factors. Methods: The Rising-VTE/NEJ037 study was a multicenter prospective observational study. Altogether, 1021 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Patients with VTE at the time of lung cancer diagnosis started treatment with edoxaban. The primary endpoint of this trial was the rate of newly diagnosed VTE after enrollment or recurrence rate 6 months after treatment initiation. Results: Data were available for 1008 patients. The median age was 70 years (range: 30-94 years), and 70.8% were men. Sixty-two patients had VTE at the time of lung cancer diagnosis, and 38 (9.9%) developed VTE at follow-up. No cases of VTE recurrence were recorded 6 months after treatment initiation with edoxaban. Major and clinically relevant non-major bleeding events occurred in 4.9% of patients and increased to 22.7% in the edoxaban treatment group. Conclusions: VTE occurrence should be monitored during lung cancer treatment. Although treatment with edoxaban was highly effective in preventing VTE recurrence, its administration should be cautiously considered because of the high bleeding rate. Trial registration: jRCTs061180025.

7.
Intern Med ; 61(11): 1663-1671, 2022.
Article in English | MEDLINE | ID: mdl-35650114

ABSTRACT

Objective Switching from mepolizumab to benralizumab has been reported to significantly improve both asthma control and the lung function. However, the data on its efficacy in elderly patients with severe eosinophilic asthma are limited. This study aimed to assess whether elderly patients with severe eosinophilic asthma could experience an improved asthma control and lung function when switching directly from mepolizumab to benralizumab. Methods In this single-center, retrospective study conducted between February 2017 and September 2018, we assessed the effect of switching the treatment directly from mepolizumab to benralizumab on eosinophil levels, exacerbation rates, and lung function. We compared the treatment responses between the two groups using either Fisher's exact test or Mann-Whitney U-test, as appropriate. Patients We enrolled 12 elderly patients (age ≥65 years) with severe eosinophilic asthma treated with mepolizumab at Hiroshima Prefectural Hospital (Hiroshima, Japan) during the study period. Six patients were switched from mepolizumab to benralizumab, and six continued with the mepolizumab treatment. Results The switch from mepolizumab to benralizumab caused a near-complete reduction in the eosinophil count (p=0.008). The annual rate of clinically relevant exacerbations and hospitalizations diminished as well, albeit with no statistical significance. We found no improvement in the lung function after switching treatment and no difference in the treatment response between the groups. Conclusion Although this study is based on a small sample of participants, the results indicate that both mepolizumab treatment and switching from mepolizumab to benralizumab treatment without a washout period have clinically relevant asthma control benefits for elderly patients with severe eosinophilic asthma.


Subject(s)
Asthma , Pulmonary Eosinophilia , Aged , Antibodies, Monoclonal, Humanized , Asthma/drug therapy , Humans , Pulmonary Eosinophilia/drug therapy , Retrospective Studies , Severity of Illness Index
8.
BMC Pulm Med ; 22(1): 260, 2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35773658

ABSTRACT

BACKGROUND: Mesenchymal-epithelial transition exon14 (METex14) skipping is one of the therapeutic driver oncogene mutations in non-small cell lung cancer (NSCLC), and can be treated with tepotinib and capmatinib. There is only one report on computed tomography (CT) findings of METex14 skipping-positive NSCLC, which shows that the primary tumor tends to have a large mass in the upper lobe, and extrathoracic metastases are common. This study examined the CT findings of METex14 skipping-positive NSCLC, focusing on the features of the margins and internal structures. METHODS: We consecutively included patients with METex14 skipping-positive NSCLC who were diagnosed between January 2018 and December 2020 at four independent institutions. We retrospectively reviewed the patient demographics and CT findings for tumor margins (invasion into surrounding tissue, lobulation, pleural indentation, spicula, and ground-glass opacity) and internal structures (air bronchograms, cavitation and internal low-density area). RESULTS: Fifteen patients with METex14 skipping-positive NSCLC were identified. Almost half of the patients were men (7/15; 46.7%), and their median age was 75.0 years. More than half were either current or former smokers (9/15; 60.0%). A vast majority of histological subtypes were adenocarcinoma (10/15; 66.7%), followed by pleomorphic carcinoma (3/15; 20.0%) and squamous cell carcinoma (2/15; 13.3%). With regard to CT findings, most primary tumors presented as masses larger than 30 mm (12/15; 80.0%) and were located in the upper lobes (12/15; 80.0%). Invasion into surrounding tissue and presence of internal low-density areas were observed in 60.0% (9/15) and 66.7% (10/15) of the primary tumors, respectively. Additionally, their frequencies increased to 72.7% (8/11) and 90.9% (10/11) in stage III/IV cases, respectively. In lymph node metastasis, internal low-density areas were observed in 8/10 cases (80.0%). Although these two CT features were rarely observed in distant metastases at diagnosis, they became apparent with progression of the metastatic tumor size. CONCLUSIONS: METex14 skipping-positive NSCLC tumors tend to invade surrounding tissue and possess internal low-density areas. These CT findings might be characteristic of METex14 skipping-positive NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Exons , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Mutation , Proto-Oncogene Proteins c-met/genetics , Retrospective Studies , Tomography, X-Ray Computed
9.
Thorac Cancer ; 13(11): 1611-1618, 2022 06.
Article in English | MEDLINE | ID: mdl-35488720

ABSTRACT

BACKGROUND: Pembrolizumab is the recommended first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥50% without driver mutations. However, its efficacy and safety for patients ≥75 years have not been prospectively investigated; this was the aim of this study. METHODS: This multicenter and open-label single-arm phase II study was conducted at 12 institutions. Chemotherapy-naïve patients with advanced NSCLC and a PD-L1 TPS of ≥50% without EGFR mutations or translocation of the ALK received pembrolizumab every 3 weeks. The primary endpoint was progression-free survival (PFS) with a threshold of 4.3 months. The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life. RESULTS: Twenty-six patients were enrolled between October 2017 and March 2020. The median PFS was 9.6 (95% confidence interval [CI] 2.1-20.6) months. The lower limit of the 95% CI did not exceed the target. The median OS was 21.6 months. The ORR and DCR were 41.7% and 70.8%, respectively. The proportion of patients with grade ≥3 treatment-related adverse events was 15.4%. The quality of life score did not change significantly during treatment. CONCLUSION: While this study showed that pembrolizumab was a tolerable treatment for elderly patients, the safety requires further confirmation in a larger study. Although the primary endpoint, the median PFS (9.6 months), was slightly shorter than that (10.3 months) of the previous phase III study (KEYNOTE-024 study), the median PFS did not achieve the expected value.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Antibodies, Monoclonal, Humanized , B7-H1 Antigen/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/pathology , Quality of Life
10.
J Hematol Oncol ; 15(1): 40, 2022 04 04.
Article in English | MEDLINE | ID: mdl-35379309

ABSTRACT

Management of cancer-associated venous thromboembolism (VTE) is essential in treatment selection and cancer prognosis. However, to date, there is no method to assess the risk of VTE specifically associated with advanced lung cancer. Our aim was to create a new risk assessment scoring system that can predict the concomitant or incidence of VTE in advanced lung cancer. We used the dataset of 1008 patients with lung cancer in the Rising-VTE/NEJ037 study, of which 100 (9.9%) developed VTE. The items extracted in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2, and diastolic blood pressure. This model had a maximum score of 8 points, with ≥ 5 points indicating a high risk of VTE. This simple risk-assessment model for VTE complications with advanced lung cancer could help identify cases that required monitoring for VTE.


Subject(s)
Lung Neoplasms , Venous Thromboembolism , Female , Humans , Lung Neoplasms/complications , Prospective Studies , Risk Assessment , Risk Factors , Venous Thromboembolism/etiology
11.
Respir Investig ; 60(3): 418-424, 2022 May.
Article in English | MEDLINE | ID: mdl-35307364

ABSTRACT

In this retrospective cohort study, we evaluated the efficacy of baricitinib in the treatment of coronavirus disease 2019 (COVID-19). Among 404 adult patients with COVID-19 who were admitted to our hospital between October 23, 2020, and July 31, 2021, 229 patients with respiratory failure were included. Among these, 41 patients in the baricitinib group and 41 patients in the control group were selected by propensity score matching to adjust for background factors. We compared the survival rates of the two groups at 30 and 60 days after admission. The 30-day survival rate was significantly higher in the baricitinib group than in the control group. However, there was no significant difference in 60-day survival in the two groups. Baricitinib may improve the early prognosis of patients with respiratory failure associated with COVID-19. However, efforts should be made to improve the long-term prognosis.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Respiratory Insufficiency , Adult , Azetidines , COVID-19/complications , Humans , Propensity Score , Purines , Pyrazoles , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/etiology , Retrospective Studies , SARS-CoV-2 , Sulfonamides
12.
Geriatr Gerontol Int ; 21(10): 881-886, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34378299

ABSTRACT

AIM: Gefitinib and erlotinib are efficacious and safe for older patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, prolonged use of epidermal growth factor receptor-tyrosine kinase inhibitors in older patients is difficult, owing to potential adverse events. Hence, dose reduction or treatment discontinuation is often required. We investigated the efficacy of low-dose first-line erlotinib and its effects on the quality of life of older patients with lung cancer. METHODS: A prospective, multicenter, phase II clinical trial was carried out in patients aged ≥75 years with epidermal growth factor receptor-mutant non-small cell lung cancer. Initially, 100 mg/day erlotinib was administered orally; if well tolerated, it was increased to 150 mg/day. The primary end-point was progression-free survival, and secondary end-points were the response rate, overall survival and change in quality of life ("Care Notebook" questionnaire). RESULTS: The median progression-free survival was 17.8 months, response rate was 63.6% and median overall survival was 27.8 months. The change in the quality of life after 6 weeks was assessed in 72.7% of the patients. Fatigue, pain, anxiety and deterioration in daily activities were found in at least 40% of the patients. Despite the therapeutic effect of 100 mg/day erlotinib, many patients required dose reduction, and in some, the quality of life could not be maintained. CONCLUSIONS: Many older patients with epidermal growth factor receptor-mutant non-small cell lung cancer might require treatment dose reduction. Further studies are required to develop individualized treatments for older patients with lung cancer. Geriatr Gerontol Int 2021; 21: 881-886.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , ErbB Receptors/therapeutic use , Erlotinib Hydrochloride/therapeutic use , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Prospective Studies , Quality of Life
13.
Anticancer Drugs ; 32(7): 767-772, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33967202

ABSTRACT

Platinum doublet is the standard chemotherapy regimen for unresectable nonsmall-cell lung cancer (NSCLC) without a driver mutation. However, for squamous cell lung cancer, the most effective cytotoxic regimen is not yet established. Combination therapy of gemcitabine with a platinum agent is a highly effective treatment among the platinum doublet regimens and is promising as a treatment for advanced squamous cell lung carcinoma. In this study, we prospectively evaluated the efficacy of gemcitabine + platinum combination therapy followed by maintenance gemcitabine monotherapy in untreated advanced squamous cell lung cancer. Patients with squamous cell lung cancer received four cycles of gemcitabine + platinum combination therapy every 3 or 4 weeks. After the induction therapy, gemcitabine maintenance therapy was administered every 3 or 4 weeks until disease progression or unacceptable toxicity. Of 18 patients enrolled, the median progression-free survival was 3.9 months. Only six patients received maintenance chemotherapy with gemcitabine. The median survival time of all enrolled patients was 18.1 months. Cytopenia of any grade occurred in at least 70% of the enrolled patients. However, severe adverse events were observed in only a few cases. Gemcitabine maintenance therapy after gemcitabine plus platinum agents is a suggested treatment for unresectable squamous cell lung cancer. While the overall toxicity profile of this therapy is acceptable, attention should be paid to bone marrow suppression.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Cisplatin/therapeutic use , Deoxycytidine/analogs & derivatives , Lung Neoplasms/drug therapy , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Neoplasm Staging , Progression-Free Survival , Gemcitabine
14.
Respir Investig ; 59(4): 478-486, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33849780

ABSTRACT

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory diseases, presenting overlapping prevalence with age. Mepolizumab is a humanized monoclonal antibody targeting interleukin-5. In major randomized clinical trials, this antibody reportedly reduced the circulating eosinophil count, exacerbation rate, and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data regarding the efficacy of mepolizumab in elderly patients with asthma and overlapping COPD are limited. METHODS: This was a single-center, retrospective, observational study. Elderly patients (age ≥65 years) administered mepolizumab between August 2016 and March 2019 were enrolled and the effects of mepolizumab on the eosinophil level, exacerbation numbers, OCS dosage, and lung functions were assessed. We compared treatment responses in patients with asthma and COPD overlap (ACO) with responses observed in patients with severe asthma alone. Adverse events were also evaluated. RESULTS: Twenty patients (10 men and 10 women), with a mean age of 77.5 ± 1.3 years, were included. Mepolizumab significantly reduced the blood eosinophil count, as well as significantly decreased clinically significant exacerbation, in both populations. The OCS dosage was significantly reduced in patients treated receiving maintenance OCS therapy. However, mepolizumab did not improve lung function in either population, and no significant difference was observed in treatment responses between patients with asthma alone and ACO. CONCLUSIONS: Mepolizumab may be effective in elderly patients with eosinophilic asthma and ACO.


Subject(s)
Anti-Asthmatic Agents , Asthma , Pulmonary Disease, Chronic Obstructive , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Eosinophils , Female , Humans , Infant , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Retrospective Studies
15.
Eur J Cancer ; 149: 14-22, 2021 05.
Article in English | MEDLINE | ID: mdl-33813328

ABSTRACT

BACKGROUND: Osimertinib is now a standard treatment for patients with previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC). We here investigated whether the combination of osimertinib with cytotoxic chemotherapy might hold additive efficacy, as well as tolerability. PATIENTS AND METHODS: We conducted an open-label randomised phase 2 study to evaluate osimertinib and carboplatin-pemetrexed combination in comparison with osimertinib monotherapy in EGFR mutation-positive NSCLC patients who experienced disease progression associated with the emergence of the T790M resistance mutation of EGFR during first-line EGFR-TKI therapy. The primary endpoint was PFS, with secondary endpoints, including OS, response, and safety. Given that osimertinib was approved as a first-line treatment during the study, patient accrual was discontinued, and a final analysis was performed for the 62 enrolled patients. RESULTS: Median PFS was 15.8 months for the osimertinib monotherapy group and 14.6 months for the combination therapy group (hazard ratio of 1.09, with a 95% confidence interval of 0.51-2.32; P = .83). Median OS was not reached in either group. The overall response rate was 71.4% in the osimertinib monotherapy group and 53.6% in the combination group. The frequency or severity of known adverse events in the combination group was comparable to those with carboplatin and pemetrexed previously reported, and novel adverse events were not observed in this study. CONCLUSION: This is the first randomised study to investigate the efficacy and safety of the combination of osimertinib and cytotoxic chemotherapy for EGFR-mutated NSCLC. The addition of chemotherapy to osimertinib as a second-line treatment did not prolong survival, while it was found to be generally tolerable. This combination strategy will be further validated in the first-line setting. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCTs071180062.


Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Resistance, Neoplasm , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Acrylamides/adverse effects , Adult , Aged , Aged, 80 and over , Aniline Compounds/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Humans , Japan , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Pemetrexed/therapeutic use , Progression-Free Survival , Protein Kinase Inhibitors/adverse effects , Time Factors
16.
Respir Investig ; 59(3): 327-334, 2021 May.
Article in English | MEDLINE | ID: mdl-33386292

ABSTRACT

BACKGROUND: The risk of venous thromboembolism (VTE) is increased 7-fold in patients with cancer than in those without. Low-molecular-weight heparin is the standard treatment for cancer-associated VTE. Direct oral anticoagulants (DOACs) are not inferior to low-molecular-weight heparin with respect to the general outcome of recurrent VTE. Warfarin is associated with a risk of bleeding when used in combination with gefitinib or erlotinib which are epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). It is unclear, however, whether combination treatments with EGFR-TKIs and DOACs pose the same risk. We aimed to identify anticancer drugs and anticoagulants that can be used safely in combination, as accompanying research to an observational study on VTE incidence rates in lung cancer patients (Rising-VTE/NEJ037 study). METHODS: Twelve patients receiving EFGR-TKI monotherapy and VTE treatment were enrolled. Blood samples were collected in time series after the first dose of edoxaban, and further samples were collected within 8-15 days after administering EGFR-TKIs. The pharmacokinetics (PK) of edoxaban were analyzed using a non-compartmental model. RESULTS: Edoxaban concentrations (30 mg once daily) were measured in eight patients. PK analyses showed no significant differences before and after co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib). CONCLUSIONS: Our findings indicate that the PK of edoxaban was not considerably affected by co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib).


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Factor Xa Inhibitors/pharmacokinetics , Lung Neoplasms/metabolism , Mutation , Pyridines/pharmacokinetics , Thiazoles/pharmacokinetics , Venous Thromboembolism/drug therapy , Venous Thromboembolism/metabolism , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/genetics , Drug Interactions , Drug Therapy, Combination , ErbB Receptors/genetics , Erlotinib Hydrochloride/administration & dosage , Factor Xa Inhibitors/administration & dosage , Female , Gefitinib/administration & dosage , Humans , Lung Neoplasms/complications , Lung Neoplasms/genetics , Male , Middle Aged , Protein Kinase Inhibitors/administration & dosage , Pyridines/administration & dosage , Thiazoles/administration & dosage , Venous Thromboembolism/etiology
18.
Thorac Cancer ; 11(6): 1716-1719, 2020 06.
Article in English | MEDLINE | ID: mdl-32291904

ABSTRACT

A 90-year-old female was admitted to our hospital with a history of a dry cough. Chest computed tomography (CT) scan showed a tumor shadow, and CT-guided lung biopsy revealed squamous cell carcinoma harboring an EGFR mutation. In addition, programmed death-ligand 1 (PD-L1) was highly expressed with a tumor proportion score (TPS) of >75%. Pembrolizumab therapy in the first-line setting was not effective, and the patient died at six months from the first visit. Squamous cell lung cancers (SCLCs) with both EGFR mutation and high expression of PD-L1 are very rare.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/drug therapy , Lung Neoplasms/drug therapy , Mutation , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/secondary , ErbB Receptors/genetics , Fatal Outcome , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Lung Neoplasms/pathology
19.
Mol Clin Oncol ; 9(5): 539-544, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30345049

ABSTRACT

S-1 is an oral fluoropyrimidine agent used for the treatment of non-small-cell lung cancer (NSCLC). Although S-1 monotherapy has been reported to exhibit lesser hematotoxicity compared with other third-generation chemotherapeutics, digestive toxicity was also frequently observed. Alternate-day administration of S-1 has shown a lower rate of severe digestive toxicity than the daily standard administration in patients with NSCLC. However, the safety of alternate-day S-1 therapy in elderly patients aged 75 years or older has not been investigated. The present study was a multi-center and prospective feasibility study aimed to evaluate the safety of alternate-day S-1 therapy in elderly patients with NSCLC. The patients received S-1 orally twice daily for 4 days (Monday, Wednesday, Friday, and Sunday) every week until disease progression or unacceptable toxicity. The primary endpoint was safety, which was evaluated as the number of grade ≥3 adverse events, and the secondary endpoints were progression-free survival (PFS), 1-year survival, and disease control rate (DCR). A total of 10 patients were enrolled, but 2 patients failed to initiate the treatment protocol. Finally, 8 patients were treated with the study protocol regimen. No grade 3 or higher adverse events were observed. Four (50%) and 1 (12.5%) patient had grade 2 or lower digestive symptoms such as anorexia, diarrhea, or stomatitis and grade 1 lacrimation, respectively. Moreover, 2 (25%), 1 (12.5%), and 1 (12.5%) patients had grade 2 renal dysfunction, grade 2 ileus, and elevated blood bilirubin, respectively. The median PFS was 1.5 months (95% confidence interval: 0.9-1.8), and the 1-year survival rate was 42.9%. The DCR was 12.5%. In conclusion, alternate-day S-1 administration can be a safe treatment regimen for elderly patients with NSCLC, but its therapeutic efficacy and safety for elderly patients with NSCLC should be compared against the standard S-1 administration in a large-scale study.

20.
In Vivo ; 32(5): 1155-1160, 2018.
Article in English | MEDLINE | ID: mdl-30150438

ABSTRACT

AIM: This study was designed to evaluate the efficacy and tolerability of bevacizumab with docetaxel or pemetrexed in previously treated patients with non-squamous non-small cell lung cancer. PATIENTS AND METHODS: This study enrolled patients who had received at least one chemotherapy regimen, regardless of prior use of bevacizumab. Combinations of docetaxel or pemetrexed were chosen by attending physicians. The primary endpoint was progression-free survival, and secondary endpoints were safety, disease control rate, and overall survival. RESULTS: Thirty patients from two institutions were eligible. The median progression-free and overall survival were 5.0 months (95% confidence interval=3.2-8.8 months) and 15.8 months (95% confidence interval=10.5-19.6 months), respectively. The disease control rate was 66.7%. Treatments were well tolerated, but the development rate of osteonecrosis of the jaw was 10%. CONCLUSION: Addition of bevacizumab in a salvage setting might be effective, but the development of osteonecrosis of the jaw needs to be monitored.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Bevacizumab/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Neoplasm Staging , Recurrence , Retreatment , Salvage Therapy , Treatment Outcome , Tubulin Modulators/administration & dosage
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