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Cancer Chemotherapy and Pharmacology Nov 2019Amrubicin and cisplatin is one of the active regimens used to treat patients with extensive-disease (ED)-small cell lung cancer (SCLC), whereas combined therapy...
BACKGROUND
Amrubicin and cisplatin is one of the active regimens used to treat patients with extensive-disease (ED)-small cell lung cancer (SCLC), whereas combined therapy involving chemotherapy and concurrent thoracic radiotherapy is the standard treatment for limited-disease (LD)-SCLC.
PURPOSE
This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of amrubicin and cisplatin with concurrent thoracic radiotherapy (TRT) for LD-SCLC.
PATIENTS AND METHODS
Patients that fulfilled the following eligibility criteria were enrolled: being aged ≤ 75 years and chemotherapy-naïve and having a performance status (PS) of 0-1, LD-SCLC, and adequate organ function. The patients received escalating doses of amrubicin on days 1, 2, and 3, and a fixed 60-mg/m dose of cisplatin on day 1. Four cycles of chemotherapy were administered, with each cycle lasting 4 weeks. TRT involving 2 Gy/day, once daily, commenced on day 2 of the first cycle of chemotherapy. The initial dose of amrubicin was 20 mg/m (level 1), and the dose was escalated to 25 mg/m (level 2) and then 30 mg/m (level 3).
RESULTS
Eight patients from three institutions were enrolled at three dose levels. The patients' characteristics were as follows: male/female: 3/5; median age (range): 68.5 (60-73); PS 0/1: 4/4; stage IIIA/IIIB disease: 3/5. Both level 3 patients experienced DLT (grade 4 neutropenia and/or leukopenia lasting > 4 days). Level 3 was defined as the MTD, and level 2 was recommended as the dose for this regimen. Seven patients exhibited partial responses, and 1 displayed progressive disease (response rate: 88%). The median progression-free survival and overall survival periods were 11.1 and 39.5 months, respectively. No treatment-related deaths occurred.
CONCLUSIONS
When this regimen was combined with TRT for LD-SCLC, the MTD was 30 mg/m for amrubicin and 60 mg/m for cisplatin. In addition, neutropenia and leukopenia were DLT, and doses of 25 mg/m for amrubicin and 60 mg/m for cisplatin are recommended for this regimen.
Topics: Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Progression-Free Survival; Small Cell Lung Carcinoma; Survival Rate
PubMed: 31486872
DOI: 10.1007/s00280-019-03940-0 -
Japanese Journal of Clinical Oncology Jun 2023This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell...
Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.
OBJECTIVE
This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer.
METHODS
We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival.
RESULTS
The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis.
CONCLUSION
Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.
Topics: Male; Humans; Cisplatin; Etoposide; Carboplatin; Lung Neoplasms; Retrospective Studies; Small Cell Lung Carcinoma; Treatment Outcome; Prostatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36828781
DOI: 10.1093/jjco/hyad011 -
Current Oncology (Toronto, Ont.) Feb 2021Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and... (Meta-Analysis)
Meta-Analysis Review
Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.
Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) with platinum-irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum-etoposide (Pem+EP), durvalumab plus platinum-etoposide (Dur+EP), atezolizumab plus platinum-etoposide (Atz+EP), platinum-amrubicin (AP), IP, and platinum-etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Network Meta-Analysis; Programmed Cell Death 1 Receptor; Small Cell Lung Carcinoma
PubMed: 33673470
DOI: 10.3390/curroncol28020106 -
Translational Lung Cancer Research Sep 2022Topoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is...
BACKGROUND
Topoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear. In the present study, we aimed to evaluate the efficacy of second-line amrubicin in patients with relapsed SCLC who were previously treated with platinum-based chemotherapy, including topoisomerase I and II inhibitors.
METHODS
This study retrospectively analyzed patients with ES-SCLC who experienced recurrence and were treated with amrubicin at 22 institutions in Japan between April 2015 and November 2020. The progression-free survival of amrubicin monotherapy was investigated using the Kaplan-Meier method.
RESULTS
A total of 320 patients were enrolled in this study, with 59 (18%) receiving platinum plus topoisomerase I inhibitor irinotecan and 261 (82%) receiving platinum plus topoisomerase II inhibitor etoposide as first-line treatment. The progression-free survival of amrubicin was significantly longer in the irinotecan group than in the etoposide group (3.2 2.5 months; P=0.034).
CONCLUSIONS
These results showed that different types of topoisomerase inhibitors could affect the efficacy of amrubicin monotherapy in the second-line treatment of patients with relapsed ES-SCLC.
PubMed: 36248326
DOI: 10.21037/tlcr-22-160 -
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 -
In Vivo (Athens, Greece) 2019To evaluate treatment efficacy of cisplatin, etoposide, and irinotecan combined therapy (PEI), platinum-rechallenge chemotherapy (Pt-Re) and amrubicin monotherapy (AMR)...
BACKGROUND/AIM
To evaluate treatment efficacy of cisplatin, etoposide, and irinotecan combined therapy (PEI), platinum-rechallenge chemotherapy (Pt-Re) and amrubicin monotherapy (AMR) for patients with sensitive relapsed small cell lung cancer (SCLC).
PATIENTS AND METHODS
We defined sensitive relapse as treatment-free interval (TFI) ≥90 days. We retrospectively collected patients' data from medical records between September 2002 and December 2016. Patients with sensitive relapsed SCLC who received second-line chemotherapy were separated into those treated with PEI, with Pt-Re, or with AMR.
RESULTS
Seventy-one patients (16 PEI group, 27 Pt-Re group, and 28 AMR group) were assessable for efficacy. No significant differences in patient characteristics were found among the three groups. The median overall survival (MST) was 29.3 months in the PEI group, 24.6 months in the Pt-Re group, and 20.6 months in the AMR group (p=0.042).
CONCLUSION
A significant difference was observed in the overall survival of patients treated with PEI, Pt-Re and AMR and the MST of PEI was the longest.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Prognosis; Recurrence; Retreatment; Retrospective Studies; Small Cell Lung Carcinoma; Treatment Outcome
PubMed: 31662561
DOI: 10.21873/invivo.11727 -
Thoracic Cancer Sep 2019The efficacy of amrubicin for relapsed small-cell lung cancer (SCLC) has been reported in previous studies. Few reports, however, describe the efficacy and survival... (Clinical Trial)
Clinical Trial
The efficacy of amrubicin third-line chemotherapy in patients with relapsed extensive-disease small-cell lung cancer: A retrospective and historical study in a single institute.
BACKGROUND
The efficacy of amrubicin for relapsed small-cell lung cancer (SCLC) has been reported in previous studies. Few reports, however, describe the efficacy and survival benefit of third-line amrubicin chemotherapy in patients with extensive disease (ED)-SCLC.
METHODS
We retrospectively analyzed the clinical records of ED-SCLC patients treated with amrubicin salvage chemotherapy as a third-line chemotherapy between January 2005 and July 2016 (salvage amrubicin group). The efficacy and toxicities of amrubicin were evaluated. Overall survival (OS) in the amrubicin salvage group was compared with OS among ED-SCLC patients treated with at least second-line chemotherapy between May 2000 and July 2016 and without subsequent amrubicin salvage chemotherapy.
RESULTS
A total of 18 patients with a median age of 70 years were analyzed in the amrubicin salvage group. The median number of treatment cycles of amrubicin was four. The response rate was 27.8% (95% confidence interval (CI), 7.1%-48.5%), and the disease control rate (DCR) was 66.7% (95% CI, 44.9%-88.4%). Median progression-free survival was 2.9 months (95% CI, 1.0-4.9 months), and median OS after an initial chemotherapy was 18.1 months (95% CI, 10.2-26.0 months). OS in the amrubicin salvage group was significantly longer than in the no-amrubicin group (n = 19; 12.6 months, 95% CI, 11.5-13.8 months, P = 0.005). The frequency of neutropenia greater than grade 3 was 72.2%, with febrile neutropenia developing in 38.9% of patients in the amrubicin salvage group.
CONCLUSIONS
Despite a high frequency of febrile neutropenia, amrubicin salvage chemotherapy may improve OS in patients with relapsed ED-SCLC.
Topics: Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Salvage Therapy; Small Cell Lung Carcinoma; Survival Rate
PubMed: 31350820
DOI: 10.1111/1759-7714.13150 -
Therapeutic Advances in Medical Oncology 2020There is no standard second-line treatment for patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma (EP-PD-NEC). This study explored... (Review)
Review
BACKGROUND
There is no standard second-line treatment for patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma (EP-PD-NEC). This study explored data evaluating second-line treatment in these patients.
METHODS
A search of MEDLINE and EMBASE identified studies reporting survival and/or response data for patients with EP-PD-NEC receiving second-line therapy. Association between various factors (age, gender, ECOG performance status, primary tumour location, morphology, Ki-67, treatment and grade 3/4 haematological toxicity) and response rate (RR), progression-free (PFS) and overall survival (OS) were assessed with a mixed effects meta-regression weighted by individual study sample size. Due to a small sample size, associations were reported quantitatively, based on magnitude of beta coefficient rather than statistical significance.
RESULTS
Of 83 identified studies, 19 were eligible, including 4 prospective and 15 retrospective studies. Analysis comprised 582 patients, with a median number of 19 patients in each study (range 5-100). Median age was 59 years (range 53-66). Median RR was 18% (range 0-50; 0% for single-agent everolimus, temozolomide, topotecan; 50% with amrubicin), median PFS was 2.5 months (range 1.15-6.0) and median OS was 7.64 months (range 3.2-22.0). Studies with a higher proportion of patients with a Ki-67>55% had lower RR (β = -0.73) and shorter OS (β = -0.82).
CONCLUSION
Second-line therapy for patients with advanced EP-PD-NEC has limited efficacy and the variety of regimens used is diverse. Ki-67>55% is associated with worse outcomes. Prospective randomised studies are warranted to enable exploration of new treatment strategies.
PubMed: 32426044
DOI: 10.1177/1758835920915299 -
Lung Cancer (Amsterdam, Netherlands) Nov 2019There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation...
OBJECTIVES
There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor.
MATERIALS AND METHODS
This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1-3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients.
RESULTS
A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%-32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient.
CONCLUSION
Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.
Topics: Anthracyclines; Antineoplastic Agents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Non-Randomized Controlled Trials as Topic; Patient Selection; Prognosis; Prospective Studies; Salvage Therapy; Survival Rate; Thymoma; Thymus Neoplasms
PubMed: 31557562
DOI: 10.1016/j.lungcan.2019.09.015 -
Thoracic Cancer May 2022We conducted a phase II study of carboplatin plus nab-paclitaxel for the treatment of small cell lung cancer (SCLC) after the failure of a prior standard chemotherapy...
BACKGROUND
We conducted a phase II study of carboplatin plus nab-paclitaxel for the treatment of small cell lung cancer (SCLC) after the failure of a prior standard chemotherapy containing platinum, etoposide, irinotecan, and amrubicin if indicated. Patients with interstitial pneumonia complications were included in the study.
METHODS
Patients received 100 mg/m of nab-paclitaxel weekly (on days 1, 8, and 15) and an AUC 5 of carboplatin on day 1. The study treatment was repeated every 3 weeks until disease progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate.
RESULTS
A total of 21 patients were enrolled, all of whom were eligible for inclusion in the analysis. Twelve patients had pre-existing interstitial pneumonia. The overall response rate was 19.0% (90% confidence interval [CI]: 6.8%-38.4%). The lower limit of the 90% CI for the response rate did not exceed the prespecified threshold value of 10%. Among the 12 patients with pre-existing interstitial pneumonia, the response rate was 25%. The median progression-free survival time was 2.5 months (95% CI: 1.5-3.4 months), and the median survival time was 5.1 months (95% CI: 2.1-8.1 months). Two patients developed interstitial lung disease; both of these patients had pre-existing interstitial pneumonia. One of the patients died from interstitial lung disease.
CONCLUSION
Combination chemotherapy with carboplatin plus nab-paclitaxel for recurrent SCLC had a modest activity, although the primary study endpoint was not met. Further investigation of this regimen for patients with recurrent SCLC and interstitial pneumonia is warranted.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Neoplasm Recurrence, Local; Paclitaxel; Small Cell Lung Carcinoma
PubMed: 35318811
DOI: 10.1111/1759-7714.14394