Efficacy and safety of amrubicin hydrochloride for the treatment of relapsed small cell lung cancer (SCLC): Clinical data and presentation of results

Regarding overall survival of refractory Small-cell lung cancer (SCLC) patients, long-term survival is quite uncommon, with less than 25% of patients with limited-stage, and 1-2 % of patients with extensive-stage disease remaining alive at 5 years. Recent clinical studies demonstrated the promising efficacy of amrubicin for patients with relapsed SCLC, and this review presents the results of clinical studies showing the efficacy and safety of amrubicin for the treatment of relapsed SCLC. Amrubicin is a completely synthetic anthracycline agent with a similar structure to doxorubicin, in which the hydroxyl group at position 9 is replaced by an amino group in amrubicin to enhance efficacy. It is converted to an active metabolite, amrubicinol, which is 5-54 times more active than amrubicine. Amrubicine and amrubicinol are inhibitors of DNA topoisomerase II, developing their cytotoxic effects by stabilizing a topoisomerase II-mediated cleavable complex. Toxicities of amrubicin are similar to that of doxorubicin, however, amrubicin shows almost no cardiotoxicity. Amrubicin was administered intravenously at a dose of 35-40 mg/m on days 1 to 3 every 3 weeks. The response rate was 34-52% and the median survival times were 8.1-12.0 months. Common adverse events were hematologic toxicities, including neutropenia, leucopenia, anemia, thrombocytopenia, and febrile neutropenia. Non-hematologic adverse events included grade 3-4 anorexia, asthenia, hyponatremia and nausea. The results of the studies which demonstrated the efficacy of monotherapy for relapsed SCLC involved mainly Japanese patients. Therefore, it is necessary to conduct clinical studies more in non-Japanese patients to confirm the amrubicin efficacy.