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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 -
IJU Case Reports Mar 2024Small cell bladder cancer is a relatively rare tumor, representing <1% of all bladder tumors. Amrubicin monotherapy is used as second-line treatment for small cell lung...
INTRODUCTION
Small cell bladder cancer is a relatively rare tumor, representing <1% of all bladder tumors. Amrubicin monotherapy is used as second-line treatment for small cell lung cancer in Japan.
CASE PRESENTATION
A 79-year-old woman presented with gross hematuria and was diagnosed with small cell bladder cancer (T2 or higher). Neoadjuvant chemotherapy with etoposide and cisplatin resulted in a partial response. Robot-assisted radical cystectomy was performed, and radical resection was achieved. As we identified metastasis in the pleura 1 year later, we administered carboplatin and etoposide, which resulted in a partial response. Although pembrolizumab was initiated as maintenance therapy, it was not effective. Amrubicin was given as third-line therapy, and stable disease was achieved without serious adverse effect for 6 months.
CONCLUSION
Although there is no established treatment for metastatic small cell bladder cancer, the current case report suggests the effectiveness of amrubicin in this setting.
PubMed: 38440697
DOI: 10.1002/iju5.12684 -
IScience Mar 2024Cardiotoxicity remains a major cause of drug withdrawal, partially due to lacking predictability of animal models. Additionally, risk of cardiotoxicity following...
Cardiotoxicity remains a major cause of drug withdrawal, partially due to lacking predictability of animal models. Additionally, risk of cardiotoxicity following treatment of cancer patients is treatment limiting. It is unclear which patients will develop heart failure following therapy. Human pluripotent stem cell (hPSC)-derived cardiomyocytes present an unlimited cell source and may offer individualized solutions to this problem. We developed a platform to predict molecular and functional aspects of cardiotoxicity. Our platform can discriminate between the different cardiotoxic mechanisms of existing and novel anthracyclines Doxorubicin, Aclarubicin, and Amrubicin. Doxorubicin and Aclarubicin unlike Amrubicin substantially affected the transcriptome, mitochondrial membrane integrity, contractile force and transcription factor availability. Cardiomyocytes recovered fully within two or three weeks, corresponding to the intermittent clinical treatment regimen. Our system permits the study of hPSC-cardiomyocyte recovery and the effects of accumulated dose after multiple dosing, allowing individualized cardiotoxicity evaluation, which effects millions of cancer patients treated annually.
PubMed: 38384853
DOI: 10.1016/j.isci.2024.109139 -
Medicine International 2024The present study reports the case of a patient with acute myeloid leukemia post-cytotoxic therapy (AML-pCT) that developed following chemotherapy for thymoma. A...
The present study reports the case of a patient with acute myeloid leukemia post-cytotoxic therapy (AML-pCT) that developed following chemotherapy for thymoma. A 64-year-old female patient underwent surgical resection for a mediastinal tumor and was diagnosed with stage IVa thymoma. She received chemotherapy, including carboplatin/etoposide, carboplatin/paclitaxel and amrubicin monotherapy. At 56 months following surgery, she developed blastosis and was diagnosed with AML-pCT. As demonstrated herein, although treatment for thymoma is associated with a markedly lower frequency of myeloid neoplasms post-cytotoxic therapy (MN-pCT) than treatment for other malignancies, such as breast carcinoma, it is important to be aware that MN-pCT may occur as a late complication of thymoma treatment.
PubMed: 38283133
DOI: 10.3892/mi.2024.133 -
Thoracic Cancer Dec 2023Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia...
BACKGROUND
Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P-PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P-PEG as second-line chemotherapy for SCLC.
METHODS
We retrospectively reviewed patients with SCLC who received AMR as second-line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P-PEG in their regimen, patients (n = 60) were divided into P-PEG (n = 21) and non-P-PEG groups, and their clinical outcomes were evaluated.
RESULTS
Median of AMR treatment cycles was five (range: 1-39 cycles) in P-PEG group and four (range: 1-15 cycles) in non-P-PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P-PEG group than in the non-P-PEG group. The objective response rates were 52.4% and 30.8%, and median progression-free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P-PEG and non-P-PEG groups, respectively.
CONCLUSIONS
AMR with P-PEG as second-line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P-PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Retrospective Studies; Neoplasm Recurrence, Local; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37873674
DOI: 10.1111/1759-7714.15140 -
Cureus Aug 2023First-line and possibly repeated stereotactic radiosurgery (SRS) with preserving whole-brain radiotherapy (WBRT) is an attractive and promising option for synchronous or...
Volumetric-Modulated Arc-Based Re-radiosurgery With Simultaneous Reduced-Dose Whole-Brain Irradiation for Local Failures Following Prior Radiosurgery of Brain Oligometastases From Small Cell Lung Cancer.
First-line and possibly repeated stereotactic radiosurgery (SRS) with preserving whole-brain radiotherapy (WBRT) is an attractive and promising option for synchronous or metachronous limited brain metastases (BMs) from small cell lung cancer (SCLC), for which a modest prescription dose is generally preferred, such as a biological effective dose of ≤60 Gy, based on the linear-quadratic formula with an alpha/beta ratio of 10 (BED). In addition, the optimal planning scheme for re-SRS for local progression after SRS of BMs from SCLC remains unclear. Herein, we describe a case of limited BMs developing after a partial response to standard chemoradiotherapy (CRT) for limited-stage SCLC. The BMs, including local failures following prior single-fraction (fr) SRS, were re-treated with volumetric-modulated arc-based SRS combined with simultaneous reduced-dose WBRT. The first SRS with 36.3 Gy/3 fr (BED 80 Gy) for a small BM resulted in a local control of 17.2 months. However, the second SRS with 20 Gy/1 fr (BED 60 Gy) to the 60% or 85% isodose surface (IDS) covering the gross tumor volume (GTV) of three new BMs with a paradoxical T1/T2 mismatch, that is, a visible mass on T2 larger than an enhancing area, resulted in partial symptomatic local progression of all lesions within 5.2 months, along with the development of two new lesions, despite continued amrubicin monotherapy. In contrast, the third SRS with 53 Gy/10 fr (BED 81 Gy) to ≤74% IDSs encompassing the GTV boundary resulted in complete responses of all the lesions during six months. However, despite a combined use of WBRT of 25 Gy in the third SRS, symptomatic spinal cerebrospinal fluid dissemination and new BMs developed, the former leading to patient mortality. A BED of ≥80 Gy to the GTV margin and a steep dose increase inside the GTV boundary are suitable to ensure excellent local control in SRS for SCLC BMs. Re-SRS with the aforementioned scheme can be an efficacious option for local failures following prior SRS with a BED of ≤60 Gy. Modest dose escalation with a simultaneous integrated boost to bulky lesions in the initial CRT may reduce the development of new BM through improved control of the potential source.
PubMed: 37791190
DOI: 10.7759/cureus.44492 -
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 -
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 -
Frontiers in Oncology 2023It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.
Comparison of the second-line treatments for patients with small cell lung cancer sensitive to previous platinum-based chemotherapy: A systematic review and Bayesian network analysis.
OBJECTIVE
It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.
METHODS
We systematically screened randomized controlled trials from several online databases. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and hematological complications graded 3 to 5. The efficacy of included treatments was ranked by surface under the cumulative ranking curve (SUCRA) value.
RESULTS
We included eleven trials involving 1560 patients in quantitative analysis. Triple chemotherapy containing platinum (TP, combination of cisplatin, etoposide, and irinotecan) was associated with favorable ORR (intravenous topotecan vs TP; odds ratio: 0.13, 95% CI:0.03-0.63; SUCRA, 0.94) and PFS (vs intravenous topotecan; hazard ratio, 0.5; 95% CI: 0.25-0.99; SUCRA, 0.90). Belotecan ranked highest for OS (SUCRA, 0.90), while intravenous topotecan plus Ziv-aflibercept ranked highest for DCR (SUCRA, 0.75). TP was more likely to cause anemia and thrombocytopenia while intravenous topotecan plus Ziv-aflibercept resulted in most neutrocytopenia.
CONCLUSION
TP is the first recommendation for the second-line treatment of sensitive relapsed SCLC. TP achieved priority in ORR and PFS with the most frequent adverse effects in anemia and thrombocytopenia. For patients who cannot tolerate the hematological adverse effects of triple chemotherapy, amrubicin is an optional option. Amrubicin had relatively good ORR and PFS, accompanied by fewer hematological complications. The rechallenge of the platinum doublet is inferior to amrubicin in ORR, DCR, and PFS. Oral topotecan has a similar effect compared with IV topotecan, but oral topotecan was associated with slightly higher safety and less stress in nursing. Belotecan contributed to the best PFS with slightly better safety but was not ideal in other outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358256.
PubMed: 37007093
DOI: 10.3389/fonc.2023.1154685 -
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