Review of the Management of Relapsed Small-Cell Lung Cancer with Amrubicin Hydrochloride

Abstract

Lung cancer is the leading cause of cancer death, and approximately 15% of all lung cancer patients have small-cell lung cancer (SCLC). Although second-line chemotherapy can produce tumor regression, the prognosis is poor. Amrubicin hydrochloride (AMR) is a synthetic anthracycline anticancer agent and a potent topoisomerase II inhibitor. Here, we discuss the features of SCLC, the chemistry, pharmacokinetics, and pharmacodynamics of AMR, the results of in vitro and in vivo studies, and the efficacy and safety of AMR monotherapy and combination therapy in clinical trials. With its predictable and manageable toxicities, AMR is one of the most attractive agents for the treatment of chemotherapy-sensitive and -refractory relapsed SCLC. Numerous studies are ongoing to define the applicability of AMR therapy for patients with SCLC. These clinical trials, including phase III studies, will clarify the status of AMR in the treatment of SCLC.

Therapeutic potential and molecular mechanism of a novel sulfonamide anticancer drug, indisulam (E7070) in combination with CPT-11 for cancer treatment

“…These observations suggest that the induction pathway of topoisomerase II is more sensitive to indisulam than the regulation pathway of steady-state topoisomerase II . Similarly, synergism has been reported with combinations of topoisomerase I inhibitors and topoisomerase II inhibitors [26]. Mammalian DNA topoisomerase II is the primary target of a number of antitumor agents, such as doxorubicin, daunorubicin, VP-16, and amsacrine [27].…”

Update on small cell lung cancer management

“…In a randomised phase III trial, topotecan demonstrated a survival advantage against best supportive care [31]; and in a randomised trial against CAV, topotecan was at least equally effective [52]. Other substances which have demonstrated at least some efficacy in trials are listed in table 7, and include paclitaxel, gemcitabine and pemetrexed [17,35,37,38,43,54].…”

“…Amrubicin acts by inhibiting topoisomerase II, and is often compared with the topoisomerase I inhibitor topotecan in clinical trials [54]. The efficacy of amrubicin in Caucasian patients remains unclear, a difference which may be due to ethnic variations in enzymatic metabolism [73].…”

<p>Orphan Drugs in Development for the Treatment of Small-Cell Lung Cancer: Emerging Data on Lurbinectedin</p>

“…4 Despite the good response of first line chemotherapy in SCLC, patients generally relapse early and therapeutic options in second line treatment are limited. In sensitive disease, topotecan, which is the current standard second line treatment in Europe, irinotecan and amrubicin have shown modest activity as monotherapy, [5][6][7] while doxorubicin and ifosfamide were revealed not to be effective in refractory relapse. 8,9 Given the disappointing results in second line therapy, new therapeutic approaches are desperately needed in the field of SCLC.…”