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Cureus Aug 2023Standard whole-brain radiotherapy (WBRT) alone for large brain metastases (BMs) from small cell lung cancer (SCLC) has limited efficacy and durability, and stereotactic...
Standard whole-brain radiotherapy (WBRT) alone for large brain metastases (BMs) from small cell lung cancer (SCLC) has limited efficacy and durability, and stereotactic radiosurgery (SRS) alone for symptomatic posterior fossa BMs >3 cm with satellite lesions is challenging. Herein, we describe the case of a 73-year-old female presenting with treatment-naïve SCLC and 15 symptomatic multiple BMs, including a ≥3.8-cm cerebellar mass (≥17.7 cm) and two adjacent lesions; otherwise, the SCLC was confined to the thorax. The patient was initially treated concurrently with conventional WBRT (30 Gy in 10 fractions) without boost and chemoimmunotherapy (CIT) consisting of carboplatin, etoposide, and atezolizumab. Atezolizumab was excluded during irradiation. Five months after WBRT, the large cerebellar lesion had remarkably regressed, and the smaller lesions (≤17 mm) showed complete responses (CRs) without local progression at 20 months. However, six and 16 months after WBRT, the thoracic lesions had progressed, and although amrubicin was administered, four new BMs, including pons involvement, had developed, respectively. Despite the CRs of the four BMs following SRS (49.6 Gy in eight fractions) and the sustained regression of the thoracic lesions, meningeal dissemination and multiple new BMs were evident 3.5 months post-SRS. The small remnant of the large BM and/or newly developed BMs abutting the cerebrospinal fluid (CSF) space could have led to CSF dissemination, the presumed cause of the patient's death. Taken together, concurrent chemo-WBRT and subsequent CIT can provide excellent and durable tumor responses for SCLC BMs, but may not be fully sufficient for BMs ≥3.8 cm. Therefore, in cases with large lesions, focal dose escalation of the large lesions, consolidative thoracic radiotherapy, and dose de-escalation in the macroscopically unaffected brain region may prevent or attenuate CSF dissemination, new BM development, and adverse effects and thus should be considered.
PubMed: 37727186
DOI: 10.7759/cureus.43759 -
Efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma.Scientific Reports Apr 2024The efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) is unclear. This study aimed to evaluate the efficacy of...
The efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) is unclear. This study aimed to evaluate the efficacy of second-line chemotherapy in patients with pulmonary LCNEC. We retrospectively reviewed patients with pulmonary LCNEC or possible LCNEC (pLCNEC) who received platinum-based chemotherapy as the first-line treatment. Among these patients, we evaluated the efficacy of second-line treatment by comparing patients with small cell lung cancer (SCLC group). Of the 61 patients with LCNEC or pLCNEC (LCNEC group) who received first-line chemotherapy, 39 patients were treated with second-line chemotherapy. Among the 39 patients, 61.5% received amrubicin monotherapy. The median progression-free survival (PFS) and overall survival (OS) in the LCNEC groups were 3.3 and 8.3 months, respectively. No significant differences in the PFS (hazard ratio [HR]: 0.924, 95% confidence interval [CI] 0.647-1.320; P = 0.664) and OS (HR: 0.926; 95% CI 0.648-1.321; P = 0.670) were observed between the LCNEC and SCLC groups. In patients treated with amrubicin, the PFS (P = 0.964) and OS (P = 0.544) were not different between both the groups. Second-line chemotherapy, including amrubicin, may be considered as a treatment option for patients with pulmonary LCNEC.
Topics: Humans; Retrospective Studies; Lung Neoplasms; Anthracyclines; Small Cell Lung Carcinoma; Carcinoma, Large Cell; Carcinoma, Neuroendocrine
PubMed: 38561461
DOI: 10.1038/s41598-024-58327-w -
Thoracic Cancer Feb 2020Amrubicin chemotherapy is a treatment option for patients with non-small cell lung cancer (NSCLC) after third-line treatment in Japan. Although topoisomerase-II...
BACKGROUND
Amrubicin chemotherapy is a treatment option for patients with non-small cell lung cancer (NSCLC) after third-line treatment in Japan. Although topoisomerase-II (Topo-II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown.
METHODS
Data regarding 44 patients with advanced NSCLC treated with amrubicin between April 2004 and May 2014 were retrospectively analyzed. We evaluated the expression levels of Topo-II by immunohistochemical staining of tumor specimens obtained via biopsy or surgical resection.
RESULTS
The majority of enrolled patients were men (68%) with a median age of 67 (range, 43-78) years. The most common histological type was adenocarcinoma (70%). High Topo-II expression was observed in 13 (30%) of the 44 patients. The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS.
CONCLUSION
Low expression of Topo-II was identified as an independent prognostic factor for longer survival in patients with NSCLC receiving amrubicin, a Topo-II inhibitor.
KEY POINTS
Significant findings of the study The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS. What this study adds This study is the first to assess the effects of topoisomerase-II (Topo-II), a target of amrubicin, as a prognostic or predictive marker for chemosensitivity and clinical outcomes in the Japanese population.
Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; DNA Topoisomerases, Type II; Female; Follow-Up Studies; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Rate
PubMed: 31901017
DOI: 10.1111/1759-7714.13289 -
Therapeutic Advances in Medical Oncology 2020Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer...
BACKGROUND
Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC).
METHODS
The protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis.
RESULTS
A total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33-0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53-0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58-0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68-1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58-1.31). "Selective carboplatin or cisplatin (CBDCA/CDDP)"+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59-0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67-1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen.
CONCLUSION
Patients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.
PubMed: 33403010
DOI: 10.1177/1758835920965841 -
Cureus Apr 2023A 64-year-old man was referred from a local clinic with a chief complaint of cough. Computed tomography (CT) revealed a mass comprising a tumor in the right lower lobe...
A 64-year-old man was referred from a local clinic with a chief complaint of cough. Computed tomography (CT) revealed a mass comprising a tumor in the right lower lobe and enlarged mediastinal lymph nodes, and a whole-body workup with positron emission tomography-CT showed bilateral lymph node enlargement and cancerous pericarditis. Biopsy with bronchoscopy of the right lower lobe tumor and mediastinal lymph node confirmed the histological findings of small cell lung carcinoma. The clinical diagnosis of extensive-stage small cell lung cancer (ES-SCLC) was confirmed, and first-line treatment with carboplatin, etoposide, and atezolizumab was initiated, followed by tri-weekly atezolizumab thrice. The patient experienced worsening pleural effusion treated with thoracentesis, pleural drainage, and pleurodesis. He also experienced several recurrences, which were managed with second and third-line chemotherapy with nogitecan and amrubicin. He has been receiving third-line therapy for over 30 months since his initial visit and remains stable as of today. The patient experienced an exceptional treatment outcome considering that the prognosis of ES-SCLC remains poor, with a median survival of approximately 10 months with conventional chemotherapies using cytotoxic agents. The use of immune checkpoint inhibitors (ICI) for ES-SCLC as first-line treatment may demonstrate a persistent antitumor effect, and result in improved survival following discontinuation. In conclusion, therapy including ICI for patients with ES-SCLC is a treatment option that shows possibilities in improving survival even after discontinuation.
PubMed: 37213944
DOI: 10.7759/cureus.37757 -
Thoracic Cancer Jun 2021Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe...
BACKGROUND
Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next-generation anthracycline that is commonly used to treat lung cancer. Here, we conducted a phase II trial of this drug in patients with previously treated MPM.
METHODS
Eligible patients with MPM having adequate organ function and a performance status of 0-2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m AMR on days 1-3 every three weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Median progression-free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events were evaluated as secondary endpoints.
RESULTS
This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2-11.2) months, and the median OS was 9.1 (range, 6.2-22.0) months. The median number of treatment cycles was three (range, 2-11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia.
CONCLUSIONS
Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.
Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Female; Humans; Male; Mesothelioma, Malignant; Middle Aged; Palliative Care; Pleural Neoplasms; Young Adult
PubMed: 33830645
DOI: 10.1111/1759-7714.13892 -
Oxford Medical Case Reports Apr 2020The transformation of adenocarcinoma to small cell lung cancer has been reported as acquisition of resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase...
The transformation of adenocarcinoma to small cell lung cancer has been reported as acquisition of resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. We here report a patient who presented histologically confirmed transformation of adenocarcinoma to small cell lung cancer after treatment with immune checkpoint inhibitor. A 65-year-old man was treated with pembrolizumab as first-line therapy and achieved temporarily a stable disease with progression after six cycles of this agent. At that stage, a transbronchial biopsy showed small cell lung cancer, and he was found to have high serum concentrations of neuron-specific enolase despite concentrations of numerous tumor markers, including neuron-specific enolase, having been within normal limits at the time of presentation. The patient thereafter was treated as a small cell carcinoma patient using cisplatin plus irinotecan and amrubicin.
PubMed: 32477576
DOI: 10.1093/omcr/omaa026 -
Journal of Cancer Research and... 2020The benefits of second-line chemotherapy on the overall survival (OS) of small-cell lung cancer (SCLC) patients might be confounded by subsequent therapies. In this...
BACKGROUND
The benefits of second-line chemotherapy on the overall survival (OS) of small-cell lung cancer (SCLC) patients might be confounded by subsequent therapies. In this study, we aimed to determine the influence of progression-free survival (PFS) and postprogression survival (PPS) on OS after second-line chemotherapy in patients with refractory SCLC treated with amrubicin monotherapy.
MATERIALS AND METHODS
We analyzed the data of 35 patients with refractory SCLC who were treated with amrubicin monotherapy as second-line chemotherapy between July 2005 and December 2015. The correlations of PFS and PPS with OS were statistically analyzed at the individual level using Spearman's rank correlation and linear regression analyses.
RESULTS
The correlation between PPS and OS was strong (r = 0.88, P < 0.05, R = 0.87), while that between PFS and OS was weak (r = 0.60, P < 0.05, R = 0.15). The number of regimens administered after disease progression postsecond-line chemotherapy was significantly associated with PPS (P = 0.003).
CONCLUSIONS
OS is more strongly linked to PPS than to PFS in refractory SCLC patients who undergo amrubicin monotherapy as a second-line treatment. These results suggest that treatments administered after second-line chemotherapy affect the OS of refractory SCLC patients treated with amrubicin monotherapy.
Topics: Aged; Anthracyclines; Antineoplastic Agents; Disease Progression; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Male; Middle Aged; Progression-Free Survival; Prospective Studies; Retrospective Studies; Small Cell Lung Carcinoma; Survival Rate
PubMed: 32930116
DOI: 10.4103/jcrt.JCRT_1170_16 -
Journal of Molecular Modeling Apr 2021The COVID-19 main protease (Mpro), one of the conserved proteins of the novel coronavirus is crucial for its replication and so is a very lucrative drug target. Till...
The COVID-19 main protease (Mpro), one of the conserved proteins of the novel coronavirus is crucial for its replication and so is a very lucrative drug target. Till now, there is no drug molecule that has been convincingly identified as the inhibitor of the function of this protein. The current pandemic situation demands a shortcut to quickly reach to a lead compound or a drug, which may not be the best but might serve as an interim solution at least. Following this notion, the present investigation uses virtual screening to find a molecule which is alraedy approved as a drug for some other disease but could be repurposed to inhibit Mpro. The potential of the present method of work to identify such a molecule, which otherwise would have been missed out, lies in the fact that instead of just using the crystallographically identified conformation of the receptor's ligand binding pocket, molecular dynamics generated ensemble of conformations has been used. It implicitly included the possibilities of "induced-fit" and/or "population shift" mechanisms of ligand fitting. As a result, the investigation has not only identified antiviral drugs like ribavirin, ritonavir, etc., but it has also captured a wide variety of drugs for various other diseases like amrubicin, cangrelor, desmopressin, diosmin, etc. as the potent possibilities. Some of these ligands are versatile to form stable interactions with various different conformations of the receptor and therefore have been statistically surfaced in the investigation. Overall the investigation offers a wide range of compounds for further testing to confirm their scopes of applications to combat the COVID-19 pandemic.
Topics: Coronavirus 3C Proteases; Drug Discovery; Drug Evaluation, Preclinical; Drug Repositioning; Humans; Molecular Dynamics Simulation; Protein Conformation; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33864532
DOI: 10.1007/s00894-021-04732-1 -
[Rinsho Ketsueki] the Japanese Journal... 2020A 74-year-old man was admitted to hospital due to suspected acute leukemia. He had a history of thymic carcinoma, which had been treated with carboplatin in combination...
A 74-year-old man was admitted to hospital due to suspected acute leukemia. He had a history of thymic carcinoma, which had been treated with carboplatin in combination with either paclitaxel or amrubicin. However, the tumor remained unresponsive to these treatments. Administration of tegafur/gimeracil/oteracil (TS-1) was initiated, which resulted in tumor size reduction and a partial response. However, leukopenia persisted after the last TS-1 treatment, and four years after the initial treatment, increased blast cell counts were found in a blood film . Bone marrow analysis showed blasts with Auer rods, faggot cells, and dysplastic promyelocytes. Flow cytometry was positive for CD13, CD33, CD34, CD117, and myeloperoxidase, but negative for HLA-DR. PML-RARA fluorescence in situ hybridization was positive. Cytogenetic analysis revealed 47,XY,t (15;17) (q22;q21),+21. Thus, therapy-related acute promyelocytic leukemia (tAPL) was diagnosed. The patient achieved and maintained complete remission for more than 20 months by a de novo APL-treatment regimen including all-trans retinoic acid, arsenic trioxide and tamibarotene. Moreover, the thymic carcinoma has remained stable. Although secondary malignancies of thymic carcinoma have been previously reported, therapy-related leukemia, especially tAPL, is very rare.
Topics: Aged; Humans; In Situ Hybridization, Fluorescence; Leukemia, Promyelocytic, Acute; Male; Thymoma; Thymus Neoplasms; Translocation, Genetic
PubMed: 32908049
DOI: 10.11406/rinketsu.61.874