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1.
Oncologist ; 25(8): e1146-e1157, 2020 08.
Article in English | MEDLINE | ID: mdl-32385918

ABSTRACT

LESSONS LEARNED: The usefulness of maintenance gemcitabine (GEM) after biweekly carboplatin + GEM in elderly patients with non-small cell lung cancer could not be proved. Superior overall survival was obtained in the group that did not receive maintenance therapy. BACKGROUND: The primary objective of this randomized phase II study was to assess progression-free survival (PFS) in elderly patients with advanced non-small cell lung cancer (NSCLC) treated with gemcitabine (GEM) maintenance therapy versus best supportive care following first-line GEM plus carboplatin (CBDCA). METHODS: Elderly chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned 1:1 to the control arm or the study arm. All patients received biweekly combination therapy with GEM and CBDCA (1,000 mg/m2 GEM and CBDCA at an area under the curve [AUC] of 3 on days 1 and 15, every 4 weeks). In the study arm, patients with objective response or stable disease following three or four cycles of initial chemotherapy received maintenance GEM. RESULTS: Eighty-four patients were enrolled. The objective response rates (ORRs) were 17.5% in the control arm and 14.0% in the study arm. The most common toxicity was neutropenia (control arm: 47.5% and study arm: 69.8%). The median progression-free survivals were 4.99 months (control arm) and 4.44 months (study arm), and the median overall survivals (OSs) were 21.7 months (control arm) and 8.2 months (study arm). CONCLUSION: Our data do not support maintenance GEM after biweekly CBDCA+GEM in elderly patients with NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Humans , Lung Neoplasms/drug therapy , Treatment Outcome , Gemcitabine
2.
Oncologist ; 25(3): 208-e417, 2020 03.
Article in English | MEDLINE | ID: mdl-32162814

ABSTRACT

LESSONS LEARNED: The biweekly GEM plus CBDCA dose and schedule showed satisfactory efficacy with mild toxicities in elderly patients with advanced NSCLC. The biweekly GEM plus CBDCA regimen could be considered an alternative to the 3-week regimen in NSCLC. BACKGROUND: The gemcitabine (GEM)-carboplatin (CBDCA) combination is widely used for non-small cell lung cancer (NSCLC) and has some efficacy in elderly patients; however, a high incidence of thrombocytopenia is observed, and the optimal dosage and administration schedules are unknown. This multicenter phase II trial evaluated the efficacy and tolerability of GEM-CBDCA for elderly patients with chemotherapy-naive NSCLC. METHODS: Patients with chemotherapy-naive performance status 0-1 and with stage IIIB/IV NSCLC were administered chemotherapy biweekly (GEM 1,000 mg/m2 with CBDCA area under the blood concentration-time curve (AUC) 3 on days 1 and 15 every 4 weeks). The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty-eight patients were enrolled. Median age was 76 years (range, 70-83); 35 patients were men (73%), and 27 patients had adenocarcinoma (56%). The ORR was 29.2% (95% confidence interval [CI], 17.0-44.1). The median PFS, median OS, and 1-year survival was 5.9 months (95% CI, 4.1-6.6), 13.3 months (95% CI, 8.3-23.5), and 58%, respectively. Grade ≥3 hematological toxicities included neutropenia (29.2%), thrombocytopenia (4.2%), and anemia (20.8%). The incidence of grade ≥3 nonhematological toxicities was <5%. CONCLUSION: This GEM-CBDCA combination administered biweekly showed satisfactory efficacy with mild toxicities in elderly patients with advanced NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Female , Humans , Lung Neoplasms/drug therapy , Male , Treatment Outcome , Gemcitabine
3.
J Thorac Dis ; 11(9): 4005-4017, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31656675

ABSTRACT

BACKGROUND: M2-like/repair macrophages are thought to contribute to fibrotic process of idiopathic pulmonary fibrosis (IPF). We analyzed the association between pulmonary accumulation of M2-like macrophages and survival in IPF patients. METHODS: Lung tissues were obtained by surgical lung biopsy from patients with IPF (n=16), nonspecific interstitial pneumonia (NSIP, n=8) and control subjects (n=14). Samples were also obtained at autopsy from 9 patients who died of acute exacerbation (AE) of IPF. Lung specimens and/or human peripheral blood mononuclear cells-derived macrophages were evaluated by immunohistochemistry for expression of CD68 (pan-macrophage marker), CD163, and CD204 (M2-like macrophage markers), and by in situ mRNA hybridization and ELISA for production of transforming growth factor-ß1 (TGF-ß1). RESULTS: CD68+, CD163+, and CD204+ cell counts and CD163+/CD68+ and CD204+/CD68+ cell ratios were comparable in IPF and NSIP lung tissues and significantly higher than in control tissues. IPF-AE lung samples contained significantly elevated CD68+ and CD163+ cell counts and CD163+/CD68+ cell ratio compared with IPF samples, whereas CD204+ cell counts and CD204+/CD68+ cells ratio did not differ. High CD163+/CD68+ and CD204+/CD68+ cell ratios were significantly associated with shorter overall survival and time-to-AE in IPF patients. In vitro-differentiated human CD163+ and CD204+ macrophages both secreted TGF-ß1; however, the novel IPF drug pentraxin 2/serum amyloid protein could suppress secretion only by CD204+ macrophages. CONCLUSIONS: Pulmonary accumulation of CD163+ and CD204+ macrophages is associated with worse clinical course in IPF patients. Suppression of macrophage activation and TGF-ß1 secretion may be a potential therapeutic target for IPF.

4.
Lung Cancer ; 136: 45-51, 2019 10.
Article in English | MEDLINE | ID: mdl-31437663

ABSTRACT

OBJECTIVES: Immune checkpoint inhibitors (ICIs) have been established as a novel strategy for non-small cell lung cancer (NSCLC) therapy. However, a definitive biomarker that can predict response to ICI therapy remains unestablished. The prognostic nutritional index (PNI) is used to assess immune-nutritional conditions and is a prognostic factor in patients with various malignancies; however, its usefulness as a biomarker of response to ICI therapy and survival outcomes in NSCLC patients is unknown. Thus, we retrospectively analyzed the clinicopathological features of advanced-stage or recurrent NSCLC patients treated with ICI therapy to identify predictors of response to ICI therapy and investigate the effects of pretreatment PNI levels on survival after ICI therapy. MATERIALS AND METHODS: We selected 102 consecutive NSCLC patients who were treated with ICI therapy from November 2015 to February 2019. We measured their pretreatment PNI levels and performed univariate and multivariate Cox regression analyses of progression-free survival (PFS) or overall survival (OS) after ICI therapy. RESULTS: Pretreatment PNI levels were significantly associated with response to ICI therapy (objective response rate:P = 0.0131; disease control rate: P = 0.0002), PFS (P = 0.0013), and OS (P = 0.0053). In univariate and multivariate analyses of the associations between PNI, C-reactive protein (CRP) or neutrophil-lymphocyte ratio (NLR) and PFS or OS, NLR and PNI, but not CRP, are independent prognostic factors for PFS (NLR: relative risk [RR]=1.655, 95% confidence interval [CI]: 1.012-2.743, P = 0.0449, PNI: RR=1.704, 95% CI: 1.039-2.828, P = 0.0346). Only PNI showed a trend towards being an independent prognostic factor for OS (RR=1.606, 95% CI: 0.952-2.745, P = 0.0761). CONCLUSION: The pretreatment PNI has the potential to be a simple and novel predictive biomarker of ICI response in NSCLC patients and might help to identify patients who will obtain a survival benefit from ICI therapy.


Subject(s)
Biomarkers , Carcinoma, Non-Small-Cell Lung/epidemiology , Lung Neoplasms/epidemiology , Nutritional Status , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Molecular Targeted Therapy , Prognosis
5.
Oncologist ; 24(11): 1420-e1010, 2019 11.
Article in English | MEDLINE | ID: mdl-31332099

ABSTRACT

LESSONS LEARNED: This clinical trial, evaluating the efficacy and safety of a carboplatin plus paclitaxel regimen in a biweekly or weekly schedule instead of the more toxic 3-weekly administration, showed that the weekly regimen was better in efficacy than the biweekly regimen, with mild toxicities, for patients with non-small cell lung cancer (NSCLC).The weekly carboplatin plus paclitaxel regimen could be considered as an alternative to the 3-weekly regimen in Japanese patients with NSCLC. BACKGROUND: Combination therapy comprising carboplatin (C) and paclitaxel (P) is the most commonly used regimen for the treatment of advanced non-small cell lung cancer (NSCLC). Common toxicities associated with the regimen, such as neuropathy and myelosuppression, cause its discontinuation. In the present study, we conducted a clinical trial evaluating the efficacy of biweekly (B) and weekly (W) PC therapy to identify the appropriate chemotherapy schedule for Asian patients. METHODS: Chemonaive patients with IIIB/IV NSCLC and a performance status of 0-1 were randomly assigned to a biweekly regimen (paclitaxel 135 mg/m2 with carboplatin area under the curve [AUC] 3 on days 1 and 15 of every 4 weeks) or to a weekly regimen (paclitaxel 90 mg/m2 on days 1, 8, and 15 with carboplatin AUC 6 on day 1 of every 4 weeks). RESULTS: A total of 140 patients were enrolled in the study. The objective response rates (ORRs) were 28.1% (B) and 38.0% (W). The most common toxicity was neutropenia, with incidence rates of 62.0% (B) and 57.8% (W). Progression-free survivals (PFSs) were 4.3 months (B) and 5.1 months (W), and overall survival durations were 14.2 months (B) and 13.3 months (W). CONCLUSION: The ORR and PFS in the weekly regimen were better than those in the biweekly schedule, although a statistical difference was not observed. The toxicity profile was generally mild for both regimens. The weekly CP regimen was suitable to be considered as an alternative to the current 3-weekly regimen in NSCLC treatment.


Subject(s)
Adenocarcinoma of Lung/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma of Lung/pathology , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Survival Rate
6.
Lung Cancer ; 132: 1-8, 2019 06.
Article in English | MEDLINE | ID: mdl-31097081

ABSTRACT

OBJECTIVES: To evaluate the efficacy and safety, we conducted a randomized phase II study of pemetrexed (Pem) versus Pem + bevacizumab (Bev) for elderly patients with non-squamous non-small cell lung cancer (NSqNSCLC). PATIENTS AND METHODS: The eligibility criteria were as follows: NSqNSCLC, no prior therapy, stage IIIB/IV disease or postoperative recurrence, age: ≥75 years, performance status (PS): 0-1, and adequate bone marrow function. The patients were randomly assigned (1:1 ratio) to receive Pem or Pem + Bev. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the response rate, OS, toxicities, and cost-effectiveness. RESULTS: Forty-one patients were enrolled and 40 (20 from each group) were assessable. Their characteristics were as follows: male/female = 23/17; median age (range) = 78 (75-83); stage IIIB/IV/postoperative recurrence = 1/30/9; PS 0/1 = 11/29. All cases involved adenocarcinoma. There was no significant intergroup difference in PFS and the median PFS (95% confidence interval) values of the Pem and Pem + Bev groups were 5.4 (3.0-7.4) and 5.5 (3.6-9.9) months, respectively (p = 0.66). The response rate was significantly higher in the Pem + Bev group (15% vs. 55%, p = 0.0146), and there was no significant difference in OS (median: 16.0 vs. 16.4 months, p = 0.58). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia were seen in 10 and 30, 20 and 55, and 5 and 5 cases, respectively. Drug costs were higher in the Pem + Bev group (median: 1,522,008 vs. 3,368,428 JPY, p = 0.01). No treatment-related deaths occurred. CONCLUSIONS: Adding Bev to Pem did not result in improved survival in the elderly NSqNSCLC patients. Compared with Pem + Bev, Pem monotherapy had similar effects on survival, a more favorable toxicity profile, and was more cost-effective in elderly NSqNSCLC patients. Pem monotherapy might be one of the optional regimen for NSqNSCLC patients aged ≥75 years.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Pemetrexed/therapeutic use , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Cost-Benefit Analysis , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Male , Neoplasm Staging , Prospective Studies , Survival Analysis , Treatment Outcome
7.
In Vivo ; 33(2): 477-482, 2019.
Article in English | MEDLINE | ID: mdl-30804129

ABSTRACT

BACKGROUND/AIM: A phase II trial was conducted to assess the efficacy and safety of gefitinib plus bevacizumab for EGFR mutation-positive non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomly assigned to receive either gefitinib at 250 mg/day alone or with bevacizumab at 15 mg/kg every 3 weeks. RESULTS: Ten patients were allocated to the gefitinib group (group A) and 6 to the gefitinib plus bevacizumab group (group B). Median survival time (80%CI) for progression-free survival (PFS) was 15.1 months for group A, and 5.4 months for group B. Overall survival probability at 1 year (95%CI) was 0.750 for group A, and 0.667 for group B. The response rate was 44 % for group A and 50 % for group B. Adverse events occurred at a similar frequency in both groups. CONCLUSION: PFS was shorter in group B than group A, and therefore there was no basis to proceed to a phase III trial.


Subject(s)
Bevacizumab/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Gefitinib/administration & dosage , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Female , Humans , Kaplan-Meier Estimate , Male , Mutation , Progression-Free Survival , Protein Kinase Inhibitors/administration & dosage
8.
Cancer Sci ; 110(3): 1012-1020, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30618179

ABSTRACT

Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), has been shown to improve overall survival (OS) in patients with previously treated advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%. We report safety and efficacy results from the phase 1b KEYNOTE-025 study, which evaluated pembrolizumab in Japanese patients with previously treated NSCLC. Eligible patients had histologically/cytologically confirmed advanced NSCLC with PD-L1 TPS ≥1% and had received ≥1 platinum-doublet chemotherapy. Patients received pembrolizumab 10 mg/kg once every 3 weeks for 2 years or until disease progression/unacceptable toxicity. Primary objectives were to evaluate the safety of pembrolizumab in patients with PD-L1 TPS ≥1% and the objective response rate (ORR) per RECIST version 1.1 in patients with PD-L1 TPS ≥50%. Thirty-eight patients were enrolled and received ≥1 pembrolizumab dose. The median (range) age was 66.0 (41-78) years, and 61% had received ≥2 prior systemic therapies. Eleven patients (29%) experienced grade 3-5 treatment-related adverse events (AE); 9 patients (24%) experienced immune-mediated AE and infusion reactions, with pneumonitis (11%; any grade) being most common. Among evaluable patients with PD-L1 TPS ≥50% (n = 11), ORR was 27% (95% CI, 6-61). Among evaluable patients with PD-L1 TPS ≥1% (n = 37), ORR was 22% (95% CI, 10-38). Median (95% CI) progression-free survival and OS were 3.9 (2.0-6.2) months and 19.2 (8.0-26.7) months, respectively. In summary, pembrolizumab was generally well tolerated and showed promising antitumor activity in Japanese patients with previously treated PD-L1-expressing NSCLC. Outcomes were consistent with those from the phase 3 KEYNOTE-010 study. (Trial registration number: ClinicalTrials.gov, NCT02007070.).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Aged , Asian People , Carcinoma, Non-Small-Cell Lung/metabolism , Disease-Free Survival , Female , Humans , Lung Neoplasms/metabolism , Male
9.
Anticancer Res ; 38(6): 3779-3784, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29848743

ABSTRACT

BACKGROUND/AIM: The combination of platinum-doublet chemotherapy with bevacizumab has been established as a first-line treatment option in non-elderly patients with non-squamous (non-sq) non-small cell lung cancer (NSCLC). However, the safety and efficacy of this regimen have not yet been fully established in elderly patients. PATIENTS AND METHODS: Chemo-naïve patients with non-sq NSCLC, aged ≥75 years, having a good performance status (Eastern Cooperative Oncology Group performance status 0-1) and adequate organ function were considered eligible. Patients received carboplatin (area under the curve=5 mg/ml/min), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) every 3 weeks for up to 4 cycles, followed by maintenance bevacizumab. The primary endpoint was the objective response rate (ORR; target=50%, threshold=30%; Simon's two-stage design), and the secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Twelve patients were enrolled from June 2013 to July 2017. The study was closed because of slow patient accrual. The median patient age was 80 years. Eleven patients (92%) completed 4 cycles of induction chemotherapy. Seven patients achieved a partial response (PR), yielding an ORR of 58%. The median PFS was 8.4 [95% confidence interval (CI)=4.4-10.5] months, and the median OS was 33.9 (95%CI=13.2-43.3) months. Toxicities were generally mild and consistent with previous reports. There were no treatment-related deaths. CONCLUSION: A regimen comprising carboplatin and pemetrexed plus bevacizumab followed by maintenance bevacizumab is feasible and potentially efficacious in elderly patients with non-sq NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Drug Administration Schedule , Febrile Neutropenia , Female , Humans , Kaplan-Meier Estimate , Maintenance Chemotherapy/methods , Male , Neutropenia/chemically induced , Pemetrexed/administration & dosage , Pemetrexed/adverse effects , Treatment Outcome
10.
Onco Targets Ther ; 10: 5107-5113, 2017.
Article in English | MEDLINE | ID: mdl-29123409

ABSTRACT

PURPOSE: Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash. PATIENTS AND METHODS: First- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day) and minocycline (100 mg/day) were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3) diarrhea (increase of ≥7 stools/day over baseline) during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake) and $ G3 skin toxicity (severe or medically significant but not immediately life-threatening). RESULTS: A total of 29 patients (nine men and 20 women; median age, 66 years; performance status, 0/1/2: 18/10/1) were enrolled from four centers. Four patients had undergone prior treatment with chemotherapy, including gefitinib or erlotinib. In all, 20 (68.9%) patients and one (3.4%) patient had diarrhea of any grade and ≥ G3, respectively. One (3.4%) patient had ≥ G3 oral mucositis; no patients had ≥ G3 skin rash. A total of 18 (62%) of the 29 patients achieved a partial response. CONCLUSION: The present study indicated a trend in which TJ-14 reduced the risk of afatinib-induced diarrhea and minocycline reduced the risk of afatinib-induced skin rash.

11.
PLoS One ; 12(3): e0174547, 2017.
Article in English | MEDLINE | ID: mdl-28355256

ABSTRACT

The natural course of idiopathic pulmonary fibrosis (IPF) is variable. Predicting disease progression and survival in IPF is important for treatment. We previously demonstrated that serum periostin has the potential to be a prognostic biomarker for IPF. Our aim was to use monomeric periostin in a multicenter study to evaluate its efficacy in diagnosing IPF and predicting its progression. To do so, we developed a new periostin kit to detect only monomeric periostin. The subjects consisted of 60 IPF patients in a multicenter cohort study. We applied monomeric periostin, total periostin detected by a conventional kit, and the conventional biomarkers-KL-6, SP-D, and LDH-to diagnose IPF and to predict its short-term progression as estimated by short-term changes of %VC and % DL, CO. Moreover, we compared the fraction ratios of monomeric periostin to total periostin in IPF with those in other periostin-high diseases: atopic dermatitis, systemic scleroderma, and asthma. Monomeric periostin showed the greatest ability to identify IPF comparable with KL-6 and SP-D. Both monomeric and total periostin were well correlated with the decline of %VC and % DL, CO. Clustering of IPF patients into high and low periostin groups proved useful for predicting the short-term progression of IPF. Moreover, the relative ratio of monomeric periostin was higher in IPF than in other periostin-high diseases. Measuring monomeric periostin is useful for diagnosing IPF and predicting its short-term progression. Moreover, the ratio of monomeric periostin to total periostin is elevated in IPF compared to other periostin-high diseases.


Subject(s)
Biomarkers/blood , Cell Adhesion Molecules/blood , Idiopathic Pulmonary Fibrosis/blood , Idiopathic Pulmonary Fibrosis/diagnosis , Adult , Aged , Animals , Biomarkers/chemistry , Cell Adhesion Molecules/chemistry , Cell Line , Cohort Studies , Disease Progression , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , ROC Curve
12.
Biol Pharm Bull ; 39(12): 2009-2014, 2016.
Article in English | MEDLINE | ID: mdl-27904042

ABSTRACT

Cisplatin (CDDP) combination chemotherapy is widely administered to patients with advanced lung cancer. The dose depends on multiple factors, including whether the tumor is non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). Although efficacy is limited by cisplatin-induced nephrotoxicity (CIN), little is known about the risk factors for this complication. The aim of this study was to identify the risk factors for CIN in patients with advanced lung cancer, both NSCLC and SCLC. We retrospectively reviewed clinical data for 148 patients who underwent initial chemotherapy including CDDP ≥50 mg/m2 per patient per day for the first course at Kyushu Medical Center between October 2010 and September 2013. All data were collected from the electronic medical record system. Nephrotoxicity was defined as an increase in serum creatinine concentration of at least grade 2 during the first course of CDDP chemotherapy, as described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. CIN was observed in nine patients. Univariate analysis revealed that cardiac disease and lower baseline serum albumin (Alb) values conferred a higher risk of nephrotoxicity (p<0.05). The cut-off value of Alb was 3.8 g/dL, calculated by receiver operating characteristics (ROC) curves. Multivariable logistic regression analysis revealed that cardiac disease (odds ratio=11.7; p=0.002) and hypoalbuminemia (odds ratio=6.99 p=0.025 significantly correlated with nephrotoxicity. In conclusion, cardiac disease and low baseline Alb values are possible risk factors for CIN.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/adverse effects , Kidney Diseases/chemically induced , Lung Neoplasms/drug therapy , Aged , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Creatinine/blood , Female , Heart Diseases/blood , Heart Diseases/complications , Heart Diseases/drug therapy , Humans , Kidney Diseases/blood , Kidney Diseases/complications , Lung Neoplasms/blood , Lung Neoplasms/complications , Male , Middle Aged , Risk Factors , Serum Albumin/analysis , Small Cell Lung Carcinoma/blood , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/drug therapy
13.
Respir Investig ; 54(6): 445-453, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27886856

ABSTRACT

BACKGROUND: The relationship between the histological pattern and survival in systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unclear. In patients with SSc-ILD, we investigated whether the clinical data obtained by non-invasive examinations could be used for prognostic evaluation, and attempted to clarify whether complicating acute exacerbation (AE) and the selection of pharmacological therapy were associated with survival. METHODS: Thirty-five patients with SSc-ILD, who had not been diagnosed by surgical lung biopsy were analyzed, retrospectively. The HRCT findings were evaluated by 2 radiologists and classified into "CT-UIP" or "CT-inconsistent with UIP" patterns based on whole lung interpretations. HRCT scores were calculated based on the extent of abnormality evidenced by HRCT. The log-rank test was used to determine variables, including clinical parameters and histories. RESULTS: Twelve (34%) of the 35 patients died during a median follow-up period of approximately 7.9 years. The log-rank test showed that a higher mortality was associated with higher age, a CT-UIP pattern, a higher score for ground-glass attenuation with traction bronchiectasis on HRCT, and complicating AE, whereas a lower mortality was significantly associated with the use of immunosuppressants. A CT-UIP pattern was significantly associated with a higher incidence of later AE. CONCLUSION: Treatment with immunosuppressants was associated with a longer survival, and complicating AE is a predictor of shortened survival in SSc-ILD patients. Among the clinical parameters determined by non-invasive examinations, a CT-UIP pattern and the extent of fibrotic lesions on HRCT, but not a histological pattern of UIP, may be predictors of shortened survival.


Subject(s)
Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/etiology , Scleroderma, Systemic/complications , Tomography, X-Ray Computed , Aged , Cohort Studies , Disease Progression , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/therapeutic use , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Retrospective Studies
14.
Cancer Chemother Pharmacol ; 78(3): 501-7, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27402398

ABSTRACT

OBJECTIVES: This phase II trial investigated the efficacy and safety of S-1 plus bevacizumab (SB) after failure of platinum-based chemotherapy in patients with non-squamous non-small cell lung cancer (non-sq NSCLC). METHODS: Patients with non-sq NSCLC who had undergone prior platinum-based chemotherapy, regardless of the use of bevacizumab, were eligible. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, and bevacizumab (15 mg/kg) on day 1 every 3 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS). RESULTS: Twenty-eight patients (14 males and 14 females; median age 62 years; performance status 0/1/2: 21/7/0) were accrued from 4 centers. Almost half (n = 15, 53.6 %) of these had received prior bevacizumab therapy. The median PFS and overall survival were 3.2 months [95 % confidence interval (CI) 2.2-4.0 months] and 11.4 months (95 % CI 8.9-13.9 months), respectively. Prior exposure to bevacizumab did not affect the PFS. An objective response was observed in 4 patients, the response rate and disease control rate being 14.3 and 85.7 %, respectively. The treatment was well tolerated, the most common treatment-related side effects being anorexia (75 %) and fatigue (68 %). CONCLUSION: Although SB was well tolerated, this combination did not provide any additional benefit in terms of PFS for patients with non-sq NSCLC after failure of platinum-based chemotherapy. It will be important to clarify the most suitable agent for use with bevacizumab, and the optimal timing of bevacizumab therapy for lung cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug Combinations , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Oxonic Acid/administration & dosage , Platinum Compounds/administration & dosage , Survival Rate , Tegafur/administration & dosage , Treatment Failure , Treatment Outcome
15.
Kurume Med J ; 61(1-2): 35-41, 2014.
Article in English | MEDLINE | ID: mdl-25400235

ABSTRACT

We report the case of a 60-year-old male patient who was diagnosed with metastasis from primary lung cancer to the breast. The patient presented with a mass in the right breast. Mammography, ultrasound, and magnetic-resonance imaging each suggested primary breast cancer. A core-needle biopsy of the right breast mass indicated poorly differentiated adenocarcinoma. A basic chest X-ray showed a shadow in the left upper lung. Thoraco-abdominal computed tomography revealed a mass with a diameter of 90 mm in the left superior region, the shape of which was indicative of primary lung cancer. A lung biopsy confirmed poorly differentiated adenocarcinoma. We diagnosed primary lung cancer with metastases to the bone, brain and right breast (cT2N3M1, stage IV) by imaging and histopathology. He was administered carboplatin (area under the curve 6 mg / ml) and paclitaxel (200 mg / m(2)) tri-weekly, and underwent gamma-knife treatment for the brain metastasis. The treatments reduced the primary tumor and the metastases. However, after completion of the fifth treatment cycle, he developed disseminated intravascular coagulation from septic shock, and died on the eleventh day after completing the fifth cycle of treatment. Although metastasis to the mammary gland is uncommon, especially among males, metastasis to the mammary gland should be considered when a mammary mass does not exhibit the typical characteristics of breast cancer. A correct diagnosis of metastasis to the mammary gland from lung cancer makes it possible to select the most appropriate treatment method.


Subject(s)
Adenocarcinoma/secondary , Breast Neoplasms, Male/secondary , Lung Neoplasms/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma of Lung , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy, Large-Core Needle , Breast Neoplasms, Male/drug therapy , Fatal Outcome , Humans , Lung Neoplasms/drug therapy , Magnetic Resonance Imaging , Male , Mammography , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Tomography, X-Ray Computed , Treatment Outcome
16.
Intern Med ; 52(5): 605-9, 2013.
Article in English | MEDLINE | ID: mdl-23448773

ABSTRACT

A 49-year-old man with dyspnea was found to have reticular opacities and ground-glass attenuation with traction bronchiectasis or bronchiolectasis on computed tomography. The patient met the criteria for lung-dominant connective tissue disease (LD-CTD) and histopathologically exhibited a chronic fibrotic interstitial pneumonia illustrating framework of a usual interstitial pneumonia-like pattern. Due to worsening of the disease, therapy was initiated with corticosteroids in combination with cyclosporine A. However, treatment with these drugs was ineffective. Pirfenidone and intravenous cyclophosphamide therapy also proved ineffective. The cyclosporine A was therefore switched to tacrolimus, and the patient's disease improved, allowing for a reduction in the dose of the corticosteroids. Our experience in this case suggests that treatment with tacrolimus might be useful for treating refractory LD-CTD even when histopathologically chronic fibrotic interstitial pneumonia is evident.


Subject(s)
Connective Tissue Diseases/drug therapy , Immunosuppressive Agents/therapeutic use , Lung Diseases, Interstitial/drug therapy , Tacrolimus/therapeutic use , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/pathology , Fibrosis , Humans , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Treatment Outcome
17.
Nihon Kokyuki Gakkai Zasshi ; 49(2): 116-21, 2011 Feb.
Article in Japanese | MEDLINE | ID: mdl-21400908

ABSTRACT

A 34-year-old woman developed polydipsia, polyuria, amenorrhea and loss of pubic hair in 2001, but did not seek medical advice. On September 7th, 2009, she was admitted to our hospital complaining of acute exacerbation of dyspnea on exertion. Chest computed tomography (CT) showed multiple cystic lesions, predominantly in bilateral lower lung fields. Non-segmental, diffuse ground-glass attenuated areas and thickened bronchovascular bundles were also seen in bilateral lung fields. Pathological findings of lung specimens from a surgical lung biopsy (right S6 and S8) 14 years previously showed infiltration of S100 protein-positive histiocytoid cells in the bronchiolar wall. As a result, pulmonary Langerhans cell histiocytosis (PLCH) was diagnosed. Moreover, panhypopituitarism due to LCH was identified on endocrine testing. Dyspnea on exertion, reduction of carbon-monoxide diffusing capacity (D(LCO)) and ground-glass attenuation areas on CT were improved by smoking cessation alone, and she was discharged. However, similar acute deterioration of PLCH recurred 4 months after first admission. Her dyspnea on exertion, reduction of D(LCO) and ground-glass attenuation areas on CT were improved again by 500 mg/day methylprednisolone pulse therapy for 3 days. This case was a unique combination of panhypopituitarism and the appearance and disappearance of ground-glass attenuation areas on CT, paralleling PLCH disease activity.


Subject(s)
Histiocytosis, Langerhans-Cell/complications , Hypopituitarism/etiology , Adult , Female , Humans
18.
Asian Cardiovasc Thorac Ann ; 19(1): 64-5, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21357322

ABSTRACT

A 38-year-old man reported progressive back pain 4 years after undergoing partial resection of the lung for spontaneous pneumothorax, using staples buttressed with bovine pericardium. Chest computed tomography detected a mass near the staple line. Resection of the mass was performed successfully and the pain was relieved. The excised material was identified as an inflammatory pulmonary pseudotumor caused by the buttressing material.


Subject(s)
Pericardium/transplantation , Plasma Cell Granuloma, Pulmonary/etiology , Pneumonectomy/adverse effects , Pneumothorax/surgery , Sutures/adverse effects , Adult , Animals , Back Pain/etiology , Biopsy , Cattle , Humans , Male , Plasma Cell Granuloma, Pulmonary/diagnosis , Plasma Cell Granuloma, Pulmonary/surgery , Pneumonectomy/instrumentation , Positron-Emission Tomography , Reoperation , Tomography, X-Ray Computed , Transplantation, Heterologous , Treatment Outcome
19.
Gan To Kagaku Ryoho ; 37(3): 495-7, 2010 Mar.
Article in Japanese | MEDLINE | ID: mdl-20332690

ABSTRACT

The patient was a 58-year-old male with small cell lung cancer [T2N1M1 (HEP) ED case] who was treated systemic chemotherapy with 2 courses of CDDP+CPT-11 and 3 courses of CBDCA+PTX. After 5 courses of chemotherapy, the total response was stable disease (SD). Because the primary lesion had achieved a minor response, however, liver metastasis evidenced no change. Because of his good performance status, he was immediately treated by hepatic arterial infusion chemotherapy ( HAI) using CPT-11 to control the liver metastasis. After the HAI of weekly CPT-11 during eleven months until progression of primary lung lesion, no change in size of the liver metastasis was recognized with decreasing ProGRP (18,400 -->5,800). HAI is considered very useful for disease control without progression and for good quality of life.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Liver Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Small Cell Lung Carcinoma/drug therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Hepatic Artery , Humans , Infusions, Intra-Arterial , Irinotecan , Liver Neoplasms/secondary , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage
20.
Ann Thorac Cardiovasc Surg ; 16(6): 429-31, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21263425

ABSTRACT

A 59-year-old male underwent a surgical resection of a retroperitoneum tumor in 1990 that was diagnosed as leiomyoblastoma. Thereafter he demonstrated pulmonary metastases followed by a total of 3 pulmonary resections from 1995 to 1997. In 2008, he was incidentally found to have a tumor in the left lower lobe, which was diagnosed as a metastatic perivascular epithelioid cell (PEComa) neoplasm. Retrospectively, a primary tumor and pulmonary metastases were also diagnosed as PEComa. We experienced late-onset repeated pulmonary metastasis of a PEComa.


Subject(s)
Perivascular Epithelioid Cell Neoplasms/secondary , Retroperitoneal Neoplasms/pathology , Humans , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Male , Middle Aged , Perivascular Epithelioid Cell Neoplasms/surgery , Retroperitoneal Neoplasms/surgery , Retrospective Studies , Survivors
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