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Cancer Management and Research 2020Amrubicin (AMR) is an anticancer drug for patients with relapsed small-cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC after...
PURPOSE
Amrubicin (AMR) is an anticancer drug for patients with relapsed small-cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC after chemotherapy by carboplatin plus etoposide (CE) has not been sufficiently evaluated.
PATIENTS AND METHODS
The medical records of patients with relapsed SCLC who received AMR as second-line chemotherapy were retrospectively reviewed, and their treatment outcomes were evaluated.
RESULTS
Forty-one patients with a median age of 76 years were analyzed. The overall response rate was 26.8%. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 8.1 months, respectively. While the median PFS of 4.7 and 2.8 months in the sensitive relapse and the refractory relapse group differed significantly (=0.043), respectively, the median OS of 10.7 and 6.8 months in the respective relapse groups did not indicate a statistically significant difference (=0.24). The median PFS in a group with a modified Glasgow prognostic score (mGPS) of 0 and a group with a mGPS 1 or 2 were 4.5 and 1.6 months (=0.052), respectively, and the median OS in the respective mGPS groups were 10.7 and 4.4 months (=0.034). Multivariate analysis identified good performance status, limited disease, and mGPS 0 as favorable independent predictors of PFS and OS of AMR monotherapy. Grade 3 or higher neutropenia was observed in 23 patients (56%), and febrile neutropenia was observed in nine patients (22%). Non-hematological toxic effects were relatively mild, and pneumonitis and treatment-related deaths were not observed.
CONCLUSION
AMR is an effective and feasible regimen for elderly patients with relapsed SCLC after CE therapy.
PubMed: 32606979
DOI: 10.2147/CMAR.S255552 -
Cureus Aug 2022Small cell neuroendocrine carcinoma (SNEC) rarely occurs in the head and neck and usually occurs in the lungs. We report the case of a 55-year-old Asian male with SNEC...
Small cell neuroendocrine carcinoma (SNEC) rarely occurs in the head and neck and usually occurs in the lungs. We report the case of a 55-year-old Asian male with SNEC in the oropharynx and jaundice due to pancreatic metastasis, which was successfully palliated by amrubicin (AMR), radiotherapy, and an endoscopic biliary stent. Although pancreatic metastases are known to occur at the end stage of small cell lung cancer, there are limited data on the treatment protocols for pancreatic metastases from SNEC. The main complication of SNEC for pancreatic lesions is obstructive jaundice. Palliative radiotherapy and biliary drainage may have life-prolonging effects in patients with extrahepatic biliary obstruction. It may also be a worthwhile risk to use anticancer drugs, such as AMR that are metabolized in the liver, if the obstructive jaundice is caused by tumor growth.
PubMed: 36110444
DOI: 10.7759/cureus.27872 -
OncoTargets and Therapy 2019Extensive-disease small-cell lung cancer (ED-SCLC) has been known to be rapid progression and relapse, despite highly sensitive to chemotherapy. Amrubicin (AMR), a...
Extensive-disease small-cell lung cancer (ED-SCLC) has been known to be rapid progression and relapse, despite highly sensitive to chemotherapy. Amrubicin (AMR), a third-generation synthetic anthracycline, was accepted as a feasible alternative compared with the standard first-line chemotherapy for previously untreated ED-SCLC. While, the efficacies of these amrubicin-based regimens are unsatisfactory. Our meta-analysis was performed to assess the efficacy and toxicity of first-line therapy comparing AMR and chemotherapy in patients with ED-SCLC. Electronic databases were searched for eligible trials updated on November 2018. Randomized-controlled trials assessing the efficacy and safety of AMR in ED-SCLC were included, of which the interested results were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). A total of 6 randomized controlled trials were included in this analysis. There are no significant differences in OS (OR=1.03, 95% CI=0.66-1.60, =0.91), PFS (OR=1.2, 95% CI=10.77-1.88, =0.41) or ORR (OR=1.31, 95% CI=0.90-1.92, =0.16) with AMR (OR=0.90, 95% CI=0.76-1.05, =0.17). The most common treatment-related AEs in the AMR group are leukopenia (OR=3.13, 95% CI=1.22-7.99, =0.02) and neutropenia (OR=3.25, 95% CI=1.38-7.65, =0.007). Fatigue, anemia, nausea, vomiting, diarrhea the difference between the two groups had no statistical significance. The results of our analysis indicated that AMR therapy demonstrated non-inferiority to the standard first-line chemotherapy for previously untreated ED-SCLC. Whether it can be accepted as an alternative regimen to the standard first-line chemotherapy is still warranted.
PubMed: 31303766
DOI: 10.2147/OTT.S200601 -
Case Reports in Urology 2020A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone...
A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone metastases and the irregular enlarged prostate with urinary bladder invasion. Serum prostate-specific antigen (PSA) was 544.0 ng/mL. Histological evaluation showed adenocarcinoma with the Gleason score 5 + 4, and the clinical stage was T4N1M1c as an initial diagnosis. Although androgen deprivation therapy was performed immediately, he had castration-resistant PCa after 3 months. Therefore, he received 6 courses of docetaxel chemotherapy every 3 weeks. Serum PSA was decreased to 0.2 ng/mL, and multiple metastases and prostate size were obviously reduced based on CT. He underwent robot-assisted radical prostatectomy and radiation therapy for prostatic fossa and multiple metastases. Although serum PSA level remained low, CT showed multiple liver metastases after 3 years from surgery. He received the combination therapy of cisplatin and etoposide (PE) every 4 weeks. Liver metastases had complete response. However, he visited our hospital with complaint of vomiting and a right drooping eyelid after 6 weeks from withdrawal of PE therapy. T2-weighted magnetic resonance imaging revealed multiple leptomeningeal metastases (LM). He received RT for the brain and was administered amrubicin. However, he died of PCa after 6 weeks from the diagnosis of LM.
PubMed: 33005471
DOI: 10.1155/2020/5627548 -
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 -
Investigational New Drugs Apr 2021Background Amrubicin (AMR) is a completely synthetic 9-aminoanthracycline and clinically active against non-small cell lung cancer (NSCLC). We conducted a phase I study...
Background Amrubicin (AMR) is a completely synthetic 9-aminoanthracycline and clinically active against non-small cell lung cancer (NSCLC). We conducted a phase I study of AMR and erlotinib (ERL) combination therapy in previously treated patients with advanced NSCLC and have already reported the safety and effectiveness. Methods We conducted a multi-center, single-arm phase II trial to evaluate the efficacy of AMR and ERL combination therapy in patients with previously treated, advanced NSCLC harboring wild-type EGFR, PS 0-1 and < 75 years of age. Patients were treated at 3-week intervals with AMR plus ERL. The primary endpoint was the PFS, and the secondary endpoints were the response rate (RR), disease control rate (DCR), overall survival (OS) and toxicity. The trough ERL concentration (C) was measured as an exploratory study to analyze the relationship between the efficacy/safety and pharmacokinetics. Results From June 2013 to July 2016, 25 patients were enrolled in this trial. The PFS according to the central test was 3.6 months (95% confidence interval 2.1-5.1). The RR and DCR were 24.0% and 64.0%, respectively. We had no treatment-related deaths in this study. Conclusions The PFS of AMR and ERL combination therapy was superior to that of AMR monotherapy in the historical setting, but the primary endpoint was not met in this trial. In our study, the pharmacokinetic analysis showed that the C of ERL was elevated with combination therapy. This combination therapy might be a viable treatment for previously treated NSCLC patients without a driver oncogene mutation. Clinical trial information UMIN 000010582.
Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Erlotinib Hydrochloride; Humans; Lung Neoplasms; Male; Middle Aged; Progression-Free Survival
PubMed: 33159674
DOI: 10.1007/s10637-020-01031-z -
Journal of Comparative Effectiveness... Jul 2019To estimate the comparative efficacy of nivolumab ± ipilimumab versus alternative treatments for small-cell lung cancer after at least one prior line of... (Comparative Study)
Comparative Study
To estimate the comparative efficacy of nivolumab ± ipilimumab versus alternative treatments for small-cell lung cancer after at least one prior line of chemotherapy. A systematic literature review identified six randomized controlled trials (RCTs) that could be connected in a network. The Kaplan-Meier survival curves from these RCTs were synthesized using network meta-analysis models. Aggregate-level matching was used to connect CheckMate 032 to the RCTs. CheckMate 032 was connected to the network by Amrubicin Clinical Trial-1. Nivolumab ± ipilimumab had a more durable tumor response and more favorable long-term survival versus topotecan via intravenous and versus amrubicin. Compared with chemotherapies for recurrent small-cell lung cancer, nivolumab ± ipilimumab improves response duration, which may translate to long-term survival benefits.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Humans; Ipilimumab; Kaplan-Meier Estimate; Lung Neoplasms; Nivolumab; Small Cell Lung Carcinoma; Treatment Outcome
PubMed: 31237143
DOI: 10.2217/cer-2018-0130 -
IJU Case Reports Nov 2022Small-cell carcinoma of the prostate has a poor prognosis, and treatment options for the refractory disease are unclear.
INTRODUCTION
Small-cell carcinoma of the prostate has a poor prognosis, and treatment options for the refractory disease are unclear.
CASE PRESENTATION
A 68-year-old man with prostate cancer was referred to our hospital. He was treated with combined androgen blockade (bicalutamide and degarelix acetate). The disease progressed to castration-resistant prostate cancer, but with additional treatment, prostate-specific antigen levels remained below 0.02 ng/mL. However, computed tomography revealed enlarged right inguinal lymph nodes; moreover, his neuron-specific enolase levels were elevated. Histopathologic analysis of a biopsied lymph node confirmed small-cell carcinoma. After administering cytotoxic chemotherapy (etoposide plus cisplatin and amrubicin), the patient temporarily improved before relapsing. After genetic testing of the biopsy specimen revealed a deletion, we administered the oral PARP-2 inhibitor olaparib, which has achieved partial remission for 8 months.
CONCLUSION
PARP-2 inhibition may improve the survival of patients with -positive small-cell carcinoma of the prostate.
PubMed: 36341199
DOI: 10.1002/iju5.12523 -
Thoracic Cancer May 2023Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in...
BACKGROUND
Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy.
METHODS
The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group).
RESULTS
The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001).
CONCLUSIONS
In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Retrospective Studies; Neoplasm Recurrence, Local; Disease Progression; Antineoplastic Agents; Treatment Outcome
PubMed: 36994539
DOI: 10.1111/1759-7714.14871 -
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