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The American Journal of Case Reports Jun 2024BACKGROUND Various resistance mechanisms of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) have been reported, and approximately half of the...
BACKGROUND Various resistance mechanisms of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) have been reported, and approximately half of the cases show a T790M point mutation as resistance to EGFR-TKI. In addition, 3-14% of cases of non-small cell lung cancer transform into small cell lung carcinoma (SCLC) during treatment. However, there are few reported cases in which 2 mechanisms of resistance have been observed simultaneously. This report describes a 66-year-old man with initial presentation of stage IIA right-sided lung adenocarcinoma with EGFR gene exon 21 L858R mutation and 3 years of stable disease. During treatment with erlotinib, the patient developed SCLC and adenocarcinoma with EGFR exon 21 L858R and exon 20 T790M mutation. CASE REPORT A 66-year-old man underwent right pneumonectomy plus nodal dissection 2a for right hilar lung cancer and was diagnosed with an EGFR exon21 L858R mutated lung adenocarcinoma. Three years later, pleural dissemination was observed in the right chest wall. Although erlotinib was continued for 52 months, new metastases to the right ribs were detected. Chest wall tumor resection was performed. Based on the World Health Organization classification, the patient was diagnosed with combined SCLC, with EGFR exon21 L858R and exon20 T790M mutation. The patient received 4 cycles of carboplatin plus etoposide, 14 cycles of amrubicin, and 2 cycles of irinotecan. Chemotherapy continued for 25 months. CONCLUSIONS Long-term survival was achieved by chemotherapy after transformation. Since EGFR mutation-positive lung cancer shows a variety of acquired resistances, it is important to consider the treatment strategy of performing re-biopsy.
Topics: Aged; Humans; Male; Adenocarcinoma; Adenocarcinoma of Lung; Drug Resistance, Neoplasm; ErbB Receptors; Erlotinib Hydrochloride; Lung Neoplasms; Mutation; Small Cell Lung Carcinoma; Tyrosine Kinase Inhibitors
PubMed: 38822519
DOI: 10.12659/AJCR.943466 -
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 -
International Cancer Conference Journal Apr 2024Small cell carcinoma (SCC) of the urinary bladder is a rare and highly aggressive subtype of bladder cancer. Most cases are diagnosed at advanced stages, and its...
Small cell carcinoma (SCC) of the urinary bladder is a rare and highly aggressive subtype of bladder cancer. Most cases are diagnosed at advanced stages, and its therapeutic strategy remains unestablished. Here, we report a case of bladder SCC in which multidisciplinary treatment has resulted in relatively long-term survival. A 68-year-old man presented with gross hematuria. A cystoscopy revealed an invasive bladder tumor. A transurethral resection of bladder tumor (TURBT) was performed, and the pathological diagnosis was SCC. After systemic chemotherapy using etoposide and carboplatin and subsequent TURBT, a radical cystectomy and ileal conduit were performed. Three months postoperatively, the patient had a recurrence in the para-aortic lymph node. Systemic combination chemotherapy with carboplatin plus irinotecan (CBDCA + CPT-11) was administered, followed by amrubicin and an immune checkpoint inhibitor. In addition to this treatment, radiation therapy for the metastatic region led to the reduction of pain and shrinkage of the metastatic lesion. The patient survived for 2 years after the initial diagnosis. Our report indicates that multidisciplinary treatment can be effective for SCC of the bladder, and a therapeutic strategy including the identification of novel biomarkers should be established.
PubMed: 38524643
DOI: 10.1007/s13691-023-00644-4 -
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 -
Gan To Kagaku Ryoho. Cancer &... Dec 2023A 77-year-old man visited a clinic because of nausea and chest discomfort. On blood test, hepatobiliary enzymes were elevated, and he referred to our hospital.... (Review)
Review
A 77-year-old man visited a clinic because of nausea and chest discomfort. On blood test, hepatobiliary enzymes were elevated, and he referred to our hospital. Contrast-enhanced CT revealed stenosis of the extrahepatic bile duct and brush cytology of the bile duct showed adenocarcinoma. We therefore performed pancreatoduodenectomy for extrahepatic bile duct cancer. Pathological diagnosis was small cell neuroendocrine carcinoma, pT3N2M0, Stage ⅢA. The patient did not receive adjuvant chemotherapy and 3 months later contrast-enhanced CT and MRI showed multiple liver metastases. The patient was treated with cisplatin plus irinotecan in the first-line, cisplatin plus etoposide in the second-line, and amrubicin in the third-line and accordingly he died 1 year and 3 months after the surgery. Chemotherapy for neuroendocrine carcinoma of the bile duct is recommended as in small cell lung cancer, but the prognosis is extremely poor. We report this case with a review of some of the literature.
Topics: Male; Humans; Aged; Cisplatin; Carcinoma, Neuroendocrine; Bile Ducts, Extrahepatic; Adenocarcinoma; Bile Duct Neoplasms
PubMed: 38303342
DOI: No ID Found -
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 -
Biomedical Materials (Bristol, England) Jan 2024Glioblastoma (GBM) remains a challenging malignancy due to its aggressive nature and the lack of efficacious therapeutic interventions. Nanotechnology-based approaches...
Glioblastoma (GBM) remains a challenging malignancy due to its aggressive nature and the lack of efficacious therapeutic interventions. Nanotechnology-based approaches exhibit promise in GBM treatment; however, the successful translation of these strategies from preclinical models to clinical settings is hindered by inefficient nanoparticle clearance from vital organs. Addressing this concern, we investigated the therapeutic potential of amrubicin (AMR) encapsulated within poly (lactic-co-glycolic acid) nanoparticles (AMR-PLGA-NPs) in combating temozolomide (TMZ) resistant GBM. The study demonstrated that AMR-PLGA-NPs exerted a pronounced inhibitory effect on the cellular viability and migratory capacity of TMZ-resistant GBM cells. Furthermore, these nanoparticles exhibited considerable efficacy in downregulating the PI3K/AKT signaling pathway, thereby inducing apoptosis specifically in TMZ-resistant glioma cells and glioma stem-like cells through the activation of PTEN. Notably,experimentation revealed the ability of AMR-PLGA-NPs to traverse biological barriers within murine models. Collectively, these findings underscore the potential therapeutic utility of AMR-PLGA-NPs as a versatile nanoplatform for addressing the formidable challenges posed by GBM, particularly in mitigating drug resistance mechanisms. The study substantiates the stability and safety profile of AMR-PLGA-NPs, positioning them as a promising avenue for combating drug resistance in GBM therapeutics.
Topics: Animals; Mice; Anthracyclines; Apoptosis; Brain Neoplasms; Cell Line, Tumor; Drug Resistance, Neoplasm; Glioblastoma; Glioma; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Temozolomide
PubMed: 38181444
DOI: 10.1088/1748-605X/ad1bb2 -
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