Correlation between the efficacy of amrubicin and the previous chemotherapy regimen for relapsed small cell lung cancer

Abstract

Abstract. Amrubicin has been demonstrated to be beneficial in the treatment of patients with relapsed small cell lung cancer (SCLC). The aim of the present study was to evaluate whether there is a significant difference in the efficacy of amrubicin between patients with relapsed SCLC who were previously treated with a platinum agent in combination with a topoisomerase I inhibitor, and those patients previously treated with a platinum agent in combination with a topoisomerase II inhibitor. The medical records of patients with SCLC, who were diagnosed as having relapsed following treatment with a platinum-based regimen and subsequently received amrubicin monotherapy, were retrospectively reviewed. Of a total of 48 patients with SCLC who were treated with amrubicin, the overall response rate, median progression-free survival (PFS) time and median survival time (MST) were determined to be 31.3%, 7.1 and 17.0 months, respectively. The response rate, PFS time and MST did not differ significantly between the patients treated previously with a platinum agent in combination with irinotecan, a topoisomerase I inhibitor, (36.4%, 5.7 and 11.4 months, respectively) and those treated previously with a platinum agent in combination with etoposide, a topoisomerase II inhibitor (30.0%, 4.7 and 14.8 months, respectively). The results indicate that amrubicin may be effective as a second-line chemotherapeutic agent for patients with SCLC, irrespective of which platinum agent and topoisomerase inhibitor-based chemotherapy regimen was previously administered. IntroductionSmall-cell lung cancer (SCLC) is the most aggressive type of lung cancer and has a poor prognosis (1). The standard therapy for extensive SCLC is chemotherapy with a platinum compound (carboplatin or cisplatin) administered in combination with etoposide, a topoisomerase II inhibitor (2). A Japanese phase III study [Japan Clinical Oncology Group (JCOG) 9511] investigated the clinical outcomes patients who were administered cisplatin and etoposide, compared with those who received cisplatin and irinotecan, a topoisomerase I inhibitor (3). Irrespective of the regimen selected, the majority of patients experience relapse or disease progression following an initial response to chemotherapy, and second-line therapy is subsequently required (4,5).Amrubicin is a synthetic 9-aminoanthracycline that is converted to its active metabolite, amrubicinol, through the reduction of its C-13 ketone group to a hydroxy group (6). Amrubicin and amrubicinol are topoisomerase II inhibitors, which have been demonstrated to exert antitumor activities in various human tumor xenograft models (7). The drug has been evaluated in a number of Japanese studies and reported to yield a response rate of 36-52% and a median survival time of 7-12 months when administered as a second-line treatment (8-13). The results of previous studies have indicated that amrubicin is useful for the treatment of relapsed SCLC (8-13).Few previous studies have evaluated the efficacy of amrubicin as a second-line treatmen...

Efficacy of Platinum-Based Chemotherapy for Relapsed Small-Cell Lung Cancer after Amrubicin Monotherapy in Elderly Patients and Patients with Poor Performance Status

“…A result of a phase II study evaluating the efficacy of amrubicin monotherapy for relapsed SCLC suggested that the absence of any significant difference in the PFS by amrubicin therapy was dependent on the previous platinum-and topoisomerase inhibitor-based therapies [18]. In addition, we previously reported that no significant difference was observed in the efficacy of amrubicin monotherapy according to the type of prior regimen, such as cisplatin plus irinotecan (a topoisomerase I inhibitor), or a platinum agent plus etoposide [19]. Accordingly, it may be worth noting that carboplatin plus etoposide can be expected to show effectiveness, regardless of the type of prior regimen, including amrubicin.…”

“…In addition, we previously reported that no significant difference was observed in the efficacy of amrubicin monotherapy according to the type of prior regimen, such as cisplatin plus irinotecan (a topoisomerase I inhibitor), or a platinum agent plus etoposide [19]. Accordingly, it may be worth noting that carboplatin plus etoposide can be expected to show effectiveness, regardless of the type of prior regimen, including amrubicin.…”

Influencing factors of efficacy and long‐term use of amrubicin in patients with small cell lung cancer

“…Meanwhile, the influence of pretreatment with etoposide on the efficacy of AMR has not been established. Although it has been reported to be an influencing factor, 1 conflicting data that pretreatment with etoposide is not related to efficacy have also been reported 8 . Thus, the clinical characteristics of the optimal patient population for AMR treatment remain unclear.…”