-
Oncoimmunology 2021Sequential combination of immunogenic cell death (ICD)-induced interventions with subsequent immunotherapy has shown efficacy in preclinical models and clinical...
Sequential combination of immunogenic cell death (ICD)-induced interventions with subsequent immunotherapy has shown efficacy in preclinical models and clinical evaluation. Recently, a clinical trial enrolling small cell lung cancer patients treated with amrubicin together with PD-1 blockade confirmed the notion that ICD sensitizes tumors to immune checkpoint inhibitors.
Topics: Humans; Immunogenic Cell Death; Immunotherapy; Lung Neoplasms; Programmed Cell Death 1 Receptor; Small Cell Lung Carcinoma
PubMed: 34745770
DOI: 10.1080/2162402X.2021.1996686 -
Journal of Rural Medicine : JRM Oct 2021The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate...
The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy. We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital. The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18-51), and 112 days (95% CI = 55-267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections. The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.
PubMed: 34707735
DOI: 10.2185/jrm.2021-014 -
JTO Clinical and Research Reports Jul 2021In patients with relapsed SCLC, amrubicin (AMR) is the current standard treatment in Japan. Nevertheless, its efficacy is not satisfactory and prognosis is poor....
INTRODUCTION
In patients with relapsed SCLC, amrubicin (AMR) is the current standard treatment in Japan. Nevertheless, its efficacy is not satisfactory and prognosis is poor. Preclinical study suggested that anthracycline agent might induce immunogenic cell death and work synergistically with immune checkpoint inhibitors.
METHODS
Patients with relapsed SCLC who relapsed after completion of platinum-containing regimen were registered. Patients were treated with pembrolizumab (200 mg, flat dose on d 1, every 3 wk for 2 y) plus AMR (40 mg/m on d 1-3, every 3 wk until progression). Primary end point was overall response rate (ORR). Secondary end points consisted of progression-free survival (PFS), overall survival, and safety. On the basis of the hypothesis that this treatment will improve ORR from 20% to 40% (0.1 of one-sided α and power of 0.8), 25 patients are required (trial identifier: NCT03253068).
RESULTS
Between November 2017 and October 2019, a total of 25 patients were enrolled. Most participants (88%) relapsed within 90 days after platinum-containing therapy and all patients were immune checkpoint inhibitor-naive. ORR, the primary end point, was 52.0% (95% confidence interval [CI]: 31.3%-72.2%). Median PFS was 4.0 months (95% CI: 2.8-7.0 mo), and PFS rate at 1 year was 14.4%. Median overall survival was 10.6 months (95% CI: 7.3-21.3 mo). Common adverse events greater than or equal to grade 3 were neutropenia (64%), leukopenia (40%), and febrile neutropenia (16%). No treatment-related deaths occurred.
CONCLUSIONS
Among patients with relapsed SCLC, pembrolizumab plus AMR was effective and tolerable.
PubMed: 34590034
DOI: 10.1016/j.jtocrr.2021.100184 -
Journal of Clinical Medicine Sep 2021Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression.
Real-World Incidence of Febrile Neutropenia among Patients Treated with Single-Agent Amrubicin: Necessity of the Primary Prophylactic Administration of Granulocyte Colony-Stimulating Factor.
BACKGROUND
Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression.
PURPOSE
The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies.
PATIENTS AND METHODS
The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed.
RESULTS
One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32-86); male/female: 126/30; performance status (0/1/2): 9/108/39; SCLC/NSCLC/others: 111/30/15; and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, = 0.025).
CONCLUSIONS
The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy.
PubMed: 34575334
DOI: 10.3390/jcm10184221 -
Cureus Jul 2021Mixed adeno-neuroendocrine carcinomas (MANEC) is a rare pathological diagnosis characterized by the presence of both adeno-carcinomatous and neuroendocrine... (Review)
Review
Mixed adeno-neuroendocrine carcinomas (MANEC) is a rare pathological diagnosis characterized by the presence of both adeno-carcinomatous and neuroendocrine differentiation with each component comprising 30% of the tumor. This literature review is aimed at the extraction of all existing clinical studies and reviews on colorectal MANEC so as to ensure that a suitable chemotherapeutic regimen is chosen to improve survival outcomes and prognosis of the disease. Parallel search strategies were employed to extract past 10 years articles from PubMed, PubMed Central and Google Scholar databases. A total of 30 records consisting of one clinical trial, five retrospective cohort studies, one case control study, one case series, 16 case reports and six review papers were shortlisted. Chemotherapeutic regimens that were administered as an adjuvant and a neoadjuvant therapy were analyzed with their survival outcomes. The overall survival rate of those administered with neoadjuvant and adjuvant therapy can be as high as 57.4% and 69%, respectively. Multiple chemotherapeutic regimens were employed in colorectal MANEC and superiority of one regimen over the other can't be established. Any drug or combination of drugs that is responsive against either of the MANEC components is found to be effective against the tumor. However, excellent responsiveness has been found with 5-fluorouracil regimens as a neoadjuvant therapy and platinum-based combinations as an adjuvant therapy. XELOX, streptozocin and S1 regimens also prove to be drugs of choice in aggressive and metastasized disease conditions. Our analysis allows for improved chemotherapeutic management of individuals with colorectal MANEC and establishes an increased potential for use of streptozocin therapy in the clinical setting. However, newer drugs like amrubicin require further research prior to describing its efficacy in colorectal MANEC.
PubMed: 34458045
DOI: 10.7759/cureus.16645 -
Thoracic Cancer Jul 2021A cisplatin plus irinotecan (CPT-11) regimen is used for patients with extensive disease small cell lung cancer (ED-SCLC). Amrubicin (AMR) is primarily used for relapsed... (Comparative Study)
Comparative Study Randomized Controlled Trial
Randomized phase 2 study comparing irinotecan versus amrubicin as maintenance therapy after first-line induction therapy for extensive disease small cell lung cancer (HOT1401/NJLCG1401).
BACKGROUND
A cisplatin plus irinotecan (CPT-11) regimen is used for patients with extensive disease small cell lung cancer (ED-SCLC). Amrubicin (AMR) is primarily used for relapsed SCLC. The HOT1401/NJLCG1401 trial, an open-label randomized phase II trial, was designed to assess the benefit of maintenance therapy in patients with ED-SCLC who responded to induction therapy.
METHODS
Patients with histologically- or cytologically-confirmed ED-SCLC were included and were treated with an induction therapy of four cycles of cisplatin (60 mg/m on day 1) plus CPT-11 (60 mg/m on days 1, 8, and 15) every four weeks. After induction therapy, patients who had nonprogressive disease were randomized to receive either maintenance CPT-11 (60 mg/m on days 1 and 8) every three weeks, or AMR (35 mg/m on days 1-3) every three weeks.
RESULTS
A total of 34 patients were enrolled; 20 patients had progressive disease or received incomplete induction chemotherapy. Finally, 14 patients were randomly assigned to receive CPT-11 (n = 7) or AMR (n = 7). This study was terminated prematurely because of low patient accrual. The overall objective response rate was 73%, the median PFS was 5.7 months (95% confidence interval [CI]: 3.6-11.8), and the median overall survival was 20.1 months (95% CI: 13.7-not reached). No statistically significant difference in progression-free survival (PFS) were noted between patients treated with CPT-11 and those treated with AMR. There were no treatment-related deaths in this study.
CONCLUSIONS
Maintenance therapy with CPT-11 or AMR after induction therapy might be effective in some patients.
Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Cisplatin; Drug Therapy, Combination; Female; Humans; Induction Chemotherapy; Irinotecan; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Small Cell Lung Carcinoma; Topoisomerase I Inhibitors; Young Adult
PubMed: 34076966
DOI: 10.1111/1759-7714.14048 -
Gan To Kagaku Ryoho. Cancer &... May 2021An 86‒year‒old man with chronic kidney disease underwent surgical resection for combined large‒cell neuroendocrine carcinoma of the left lower lobe of the...
[Postoperative Relapse of Combined Large‒Cell Neuroendocrine Carcinoma of the Lung with a Remarkable Transient Response to Amrubicin Monotherapy in an Elderly Patient-A Case Report].
An 86‒year‒old man with chronic kidney disease underwent surgical resection for combined large‒cell neuroendocrine carcinoma of the left lower lobe of the lung(pT2aN1M0, stage ⅡB). Five months later, multiple liver and bone metastases and mediastinal lymph node recurrence were detected. After 9 courses of amrubicin monotherapy(32 mg/m2 for 3 consecutive days), his tumor marker levels normalized, and radiological examination revealed a complete tumor response. Adverse events occurred, but they were tolerable except a decrease in the neutrophil count. The patient remained in good condition for several months but died of tumor relapse 22 months after the initial recurrence. Amrubicin monotherapy was considered to be one of the treatment choices for recurrent large‒cell neuroendocrine carcinoma of the lung in elderly patients.
Topics: Aged; Aged, 80 and over; Anthracyclines; Carcinoma, Neuroendocrine; Humans; Lung; Lung Neoplasms; Male; Neoplasm Recurrence, Local
PubMed: 34006713
DOI: No ID Found -
Lung Cancer (Amsterdam, Netherlands) Jun 2021Optimal second-line chemotherapy for patients with relapsed small-cell lung cancer remains debatable. In addition to topotecan or amrubicin monotherapy, re-challenge... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Optimal second-line chemotherapy for patients with relapsed small-cell lung cancer remains debatable. In addition to topotecan or amrubicin monotherapy, re-challenge with first-line platinum-doublets have been commonly used. In this study, we investigated whether platinum-doublets are suitable as second-line treatment for relapsed small-cell lung cancer.
MATERIALS AND METHODS
Studies that enrolled relapsed small-cell lung cancer and compared platinum-doublets with non-platinum-based regimens for second-line treatment were identified using PubMed and EMBASE. A meta-analysis was conducted to calculate the relative risk of objective response rate and disease control rate of the second-line chemotherapy. Subgroup analyses were conducted to focus on comparison with standard second-line regimens and sensitive relapse. Progression-free and overall survival, and adverse events were systematically reviewed.
RESULTS
Ten studies published between 2011 and 2020 were included in our analysis with a total of 1222 patients: 438 treated with platinum-doublets and 784 with non-platinum-based regimens. The objective response rates for second-line platinum-doublet and non-platinum regimens were 47.3 % [95 % CI: 40.5-54.0] and 31.5 % [95 % CI: 22.2-40.8], respectively. Patients treated with platinum-doublets had a significantly higher objective response rate than patients with non-platinum-based regimens (RR [95 % CI]: 1.527 [1.100-2.121], p = 0.011), as well as disease control rate (RR [95 % CI]: 1.152 [1.052-1.262], p = 0.002). In a subgroup analysis comparing platinum-doublets with topotecan or amrubicin, patients treated with platinum-doublets had significantly higher objective response rate and disease control rate (RR [95 % CI]: 1.663 [1.055-2.619], p = 0.028 and 1.170 [1.021-1.340], p = 0.023 respectively). Progression-free and overall survival appeared consistent with the tumor responses. Adverse events associated with platinum-doublets appeared acceptable compared with the monotherapies.
CONCLUSION
Platinum-doublet chemotherapy as second-line treatment for patients with relapsed small-cell lung cancer can be considered as a reasonable option in comparison with non-platinum regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Small Cell Lung Carcinoma
PubMed: 33894495
DOI: 10.1016/j.lungcan.2021.04.013 -
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 -
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