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Thoracic Cancer Jan 2023The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however,...
Clinical efficacy of amrubicin in patients with small cell lung cancer relapse after first-line treatment including immune checkpoint inhibitors: A retrospective multicenter study (TOPGAN 2021-01).
BACKGROUND
The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however, it is unclear whether the same is applicable for small cell lung cancer (SCLC). We evaluated the efficacy of second-line amrubicin (AMR) following first-line platinum-based chemotherapy and ICI combination therapy (chemo-ICI) in SCLC.
PATIENTS AND METHODS
We retrospectively enrolled consecutive patients with SCLC treated with AMR as a second-line following chemo-ICI as first-line between July 2019 and April 2021 from 16 institutions throughout Japan. We investigated the therapeutic effectiveness, safety, and efficacy-enhancing variables of AMR.
RESULTS
Overall, 89 patients treated with AMR after first-line chemo-ICI were analyzed. The overall response rate (ORR) was 29.2% (95% confidence intervals [CI], 20.1-39.8) and median PFS (m PFS) was 2.99 months (95% CI, 2.27-3.65). Patients who relapsed more than 90 days after receiving first-line platinum combination therapy (sensitive relapse) exhibited greater ORR (58.3% vs. 24.7%, p = 0.035) and m PFS (5.03 vs. 2.56 months, p = 0.019) than patients who relapsed in <90 days (refractory relapse). Grade 3 or higher adverse events were mainly hematological toxicity.
CONCLUSIONS
Our study suggested that the therapeutic effect of AMR was not enhanced after ICI on SCLC. However, AMR may be effective in cases of sensitive relapse after chemo-ICI. There was no increase in severe toxicity associated with AMR after ICI.
Topics: Humans; Lung Neoplasms; Immune Checkpoint Inhibitors; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Neoplasm Recurrence, Local; Small Cell Lung Carcinoma; Antineoplastic Agents; Treatment Outcome; Recurrence
PubMed: 36408699
DOI: 10.1111/1759-7714.14729 -
Gastroenterology Research and Practice 2015Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as...
Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, the role of salvage chemotherapy remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods. Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2007 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results. Eight males and two females (median age, 67 years (range, 52-78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. Median progression-free survival and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Furthermore, NEC with response for amrubicin had characteristics with a high Ki-67 index and receipt of prior chemotherapy with cisplatin and irinotecan. Grade 3-4 neutropenia and anemia were observed in four and five patients, respectively. Conclusion. Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.
PubMed: 26199623
DOI: 10.1155/2015/425876 -
Clinical Genitourinary Cancer Jun 2020
Topics: Aged; Anthracyclines; Antineoplastic Agents; Carcinoma, Small Cell; Drug Resistance, Neoplasm; Humans; Male; Middle Aged; Platinum; Prognosis; Prostatic Neoplasms
PubMed: 32005612
DOI: 10.1016/j.clgc.2019.12.017 -
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 -
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 -
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 -
Oncology 2017The aim of this study was to investigate the clinical usefulness of amrubicin therapy for patients with non-gastrointestinal (GI) non-pancreatic extrapulmonary...
OBJECTIVE
The aim of this study was to investigate the clinical usefulness of amrubicin therapy for patients with non-gastrointestinal (GI) non-pancreatic extrapulmonary neuroendocrine carcinoma (EP-NEC).
METHODS
The medical records of patients from the 2 participating institutions were retrospectively reviewed. The eligibility criteria were: patients with non-GI non-pancreatic EP-NEC who received amrubicin monotherapy after platinum-based chemotherapy. Patients in whom the platinum-free interval (interval between the last day of platinum administration and the first subsequent documentation of disease progression) was 90 days or longer were classified into the platinum-sensitive group.
RESULTS
The study was conducted in a total of 13 patients identified as eligible. The response rate was 45.4% (5/11). The median progression-free survival and overall survival were 6.0 and 10.6 months, respectively. A platinum-free interval of ≥90 days was identified as a significant predictor of a longer progression-free survival time. Grade 3 or 4 neutropenia was observed in 61.5% (8/13) of the patients. One patient died of treatment-related febrile neutropenia.
CONCLUSIONS
Amrubicin monotherapy as second-line chemotherapy after failure of first-line platinum-based chemotherapy showed good efficacy in patients with non-GI non-pancreatic EP-NEC. Neutropenia was encountered as the most serious adverse event.
Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Neuroendocrine; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Retrospective Studies; Salvage Therapy; Treatment Outcome
PubMed: 28521313
DOI: 10.1159/000475669 -
Cancer Science Dec 2006Amrubicin, a completely synthetic 9-aminoanthracycline derivative, inhibits cell growth by stabilizing a topoisomerase II-DNA complex. This study was designed to examine...
Amrubicin, a completely synthetic 9-aminoanthracycline derivative, inhibits cell growth by stabilizing a topoisomerase II-DNA complex. This study was designed to examine the apoptosis induced in human leukemia U937 cells by amrubicin and its active metabolite amrubicinol. Amrubicin, amrubicinol and other antitumor agents, such as daunorubicin and etoposide, induced typical apoptosis with characteristic nuclear morphological change and DNA fragmentation. Measuring the population of sub-G(1) phase cells, it was found that under conditions where cell growth was inhibited by either amrubicin or amrubicinol, U937 cells underwent apoptotic cell death in a dose-dependent manner accompanied by an arrest of the cell cycle at G(2)/M. Furthermore, amrubicin- and amrubicinol-induced apoptosis was mediated by the activation of caspase-3/7, but not caspase-1, preceding a loss of mitochondrial membrane potential. These results indicate that both a reduction in mitochondrial membrane potential and the activation of caspase-3/7 are key events in the apoptosis induced by amrubicin and amrubicinol as well as the other antitumor agents. In addition, studies with oligomycin suggested that the apoptosis induced by amrubicin and amrubicinol involved substantially different pathways from that triggered by daunorubicin and etoposide. Oligomycin blocked the etoposide-induced increase in the number of sub-G(1) phase cells without preventing the activation of caspase-3/7, and had no inhibitory effect on the expansion of the sub-G(1) population in daunorubicin-treated cells, whereas apoptosis-related changes caused by amrubicin and amrubicinol were suppressed in the presence of oligomycin.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Caspase 7; Cell Division; Daunorubicin; Drug Therapy, Combination; Enzyme Activation; Etoposide; G2 Phase; Humans; Membrane Potentials; Mitochondria; Tumor Cells, Cultured; U937 Cells
PubMed: 16995876
DOI: 10.1111/j.1349-7006.2006.00318.x -
Investigational New Drugs Oct 2022This study examined the activity and safety of amrubicin monotherapy among relapsed small-cell lung cancer (SCLC) patients who had previously been treated with...
This study examined the activity and safety of amrubicin monotherapy among relapsed small-cell lung cancer (SCLC) patients who had previously been treated with atezolizumab plus carboplatin and etoposide (AteCE). This retrospective study evaluated patients with relapsed SCLC who were treated with previously AteCE combination therapy followed by amrubicin monotherapy between August 2019 and May 2021. Clinical efficacy and toxicity were analyzed. Overall, 40 patients were included: 12 and 28 patients had sensitive and refractory relapse, respectively. The response rate was 32.5% (25.0% in the sensitive group and 35.7% in the refractory group). The median progression-free survival (PFS) and overall survival (OS) from the first amrubicin treatment was 3.4 months (95% CI: 1.9-4.9 months) and 9.9 months (95% CI: 4.5-11.5 months), respectively. There was no significant between-group difference in median PFS (3.6 months vs. 3.2 months, p = 0.42) or median OS (11.2 months vs. 7.3 months, p = 0.78). Grade ≥ 3 hematological adverse events occurred as follows: decreased white blood cells in 52.5% of patients; decreased neutrophil count in 57.5%; and febrile neutropenia in 10.0%. Grade 3 pneumonitis was observed in one patient. There were no treatment-related deaths. Amrubicin is feasible and effective for relapsed SCLC patients previously treated with AteCE therapy. Although immune checkpoint inhibitor treatment (ICI) does not improve the effect of amrubicin, the toxicity is not increased, suggesting that amrubicin remains effective even after ICI administration. Thus, amrubicin after AteCE could be the preferred standard chemotherapeutic choice in patients with relapsed SCLC.
Topics: Anthracyclines; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Etoposide; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Retrospective Studies; Small Cell Lung Carcinoma
PubMed: 35749041
DOI: 10.1007/s10637-022-01269-9 -
Translational Lung Cancer Research Sep 2022Although the addition of immune checkpoint inhibitors (ICIs) to platinum-doublet chemotherapy has improved the efficacy of first-line therapy in extensive-disease small...
BACKGROUND
Although the addition of immune checkpoint inhibitors (ICIs) to platinum-doublet chemotherapy has improved the efficacy of first-line therapy in extensive-disease small cell lung cancer (SCLC) patients, the best treatment option for patients with recurrent SCLC has not yet been determined. We conducted a retrospective study to evaluate the efficacy and safety of amrubicin (AMR) therapy after treatment with ICIs.
METHODS
We retrospectively assessed patients with recurrent SCLC who received AMR after chemoimmunotherapy at the Niigata Lung Cancer Treatment Group from August 2019 to February 2021.
RESULTS
This analysis included 30 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.8 (95% CI: 2.7-4.2) and 10 (95% CI: 7.4-14.8) months, respectively. The median PFS and OS did not significantly differ between the sensitive and refractory groups [PFS; 3.1 (95% CI: 1.1-4.0) 4.2 (95% CI: 2.3-4.8) months, P=0.1142, OS; 10.0 (95% CI: 5.2-14.8) 10.4 (95% CI: 3.8-NE) months, P=0.5525]. The most common adverse event was grade ≥3 neutropenia, which occurred in 22 of 30 patients (73%), and 2 patients (7%) discontinued AMR due to adverse events.
CONCLUSIONS
AMR after chemoimmunotherapy shows good clinical efficacy and safety in patients with recurrent SCLC.
PubMed: 36248339
DOI: 10.21037/tlcr-22-225