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Clinical impact of amrubicin monotherapy in patients with relapsed small cell lung cancer: a multicenter retrospective study

ABSTRACT:

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 vs. 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.

SUBMITTER: Uda S

PROVIDER: S-EPMC9554692 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Project description:PurposeAmrubicin is one of the most active chemotherapeutic drugs for small cell lung cancer (SCLC). Previous studies reported its effectiveness and severe hematological toxicity. However, the efficacy of amrubicin monotherapy in elderly patients with SCLC has not been described. The objective of this study was to investigate the feasibility of amrubicin monotherapy in elderly patients and its efficacy for relapsed SCLC.MethodsA retrospective cohort study design was used. We retrospectively evaluated the clinical effects and adverse events of amrubicin treatment in elderly (≥70 years) SCLC patients with relapsed SCLC.ResultsBetween November 2003 and September 2015, 86 patients (aged ≥70 years) received amrubicin monotherapy for relapsed SCLC at four institutions. There were 42 cases of sensitive relapse (S) and 44 of refractory relapse (R). S cases with median age of 75 years (range 70-85 years) and R cases with median age of 74 years (range 70-84 years) were included in our analysis. The median number of treatment cycles was three (range 1-9), and the response rate was 33.7% (40.5% in the S and 27.2% in the R cases). Median progression-free survival time was 4.0 months in the S and 2.7 months in the R patients (p = 0.013). Median survival time from the start of amrubicin therapy was 7.6 months in the S and 5.5 months in the R cases (p = 0.26). The frequencies of grade ≥3 hematological toxicities were as follows: leukopenia, 60.4%; neutropenia, 74.4%; anemia, 11.6%; thrombocytopenia, 16.2%; and febrile neutropenia, 17.4%. Treatment-related death was observed in one patient.ConclusionAlthough hematological toxicities, particularly neutropenia, were severe, amrubicin showed favorable efficacy, not only in the S but also in the R cases, as shown in previous studies. Amrubicin could be a preferable standard treatment in elderly patients with relapsed SCLC. These results warrant further evaluation of amrubicin in elderly patients with relapsed SCLC by a prospective trial.

Project description:BackgroundAmrubicin chemotherapy is a treatment option for patients with non-small cell lung cancer (NSCLC) after third-line treatment in Japan. Although topoisomerase-II (Topo-II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown.MethodsData regarding 44 patients with advanced NSCLC treated with amrubicin between April 2004 and May 2014 were retrospectively analyzed. We evaluated the expression levels of Topo-II by immunohistochemical staining of tumor specimens obtained via biopsy or surgical resection.ResultsThe majority of enrolled patients were men (68%) with a median age of 67 (range, 43-78) years. The most common histological type was adenocarcinoma (70%). High Topo-II expression was observed in 13 (30%) of the 44 patients. The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS.ConclusionLow expression of Topo-II was identified as an independent prognostic factor for longer survival in patients with NSCLC receiving amrubicin, a Topo-II inhibitor.Key pointsSignificant findings of the study The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS. What this study adds This study is the first to assess the effects of topoisomerase-II (Topo-II), a target of amrubicin, as a prognostic or predictive marker for chemosensitivity and clinical outcomes in the Japanese population.