Lung cancer patients given amrubicin, an anthracycline also known as SM-5887 (Calsed?, Nippon Kayaku / Celgene) as a second-line therapy had a significantly improved response rate and longer progression-free survival than patients treated with topotecan (Hycamtin?, GlaxoSmithKline), a topoisomerase I inhibitor, according to research presented at the 14th World Conference on Lung Cancer in Amsterdam, hosted by the International Association for the Study of Lung Cancer (IASLC).
Amrubicin is a third-generation, synthetic anthracycline analogue that has demonstrated substantial clinical efficacy in the treatment of small cell lung cancer. Amrubicin is a potent topoisomerase II inhibitor and is being studied as a single agent and in combination with anti-cancer therapies for a variety of solid tumors, including lung and breast cancers. Topoisomerase II is an essential enzyme that plays a role in virtually every cellular DNA process.
Anthracycline anticancer use
Anthracyclines are among the most widely used anticancer drugs in clinical use today. This class of drug includes doxorubicin, daunorubicin and epirubicin, each of which is a close analogue to the others and made semi-synthetically starting from natural products. However, using a natural product as the synthetic starting point significantly constrains the range of analogues that can be made. Topotecan, for example, is a semi-synthetic derivative of camptothecin, a natural product extracted from the bark of the tree Camptotheca acuminata.
Progression-free survival
“Amrubicin showed significant improvements in tumor shrinkage, symptom control and progression-free survival over topotecan without improving overall survival, the primary endpoint of the trial,” said principal investigator Dr. Joachim von Pawel, of the Asklepios Hospital Munich-Gauting in Germany. “However, for patients with the most difficult-to-treat small cell lung cancer, amrubicin offered an improvement in overall survival compared with topotecan.”
Better symptom control and quality of life
Second-line treatment is given to patients after the initial, or first-line, treatment has failed. In the study, 637 patients were randomized to amrubicin or to topotecan. Patients on amrubicin reported better symptom control and quality of life (Lung Cancer Symptom Scale 0.2 vs 5.6 and LCSS-SB -0.1 vs 5.2 for amrubicin and topotecan, respectively). They also reported fewer adverse events, including neutropenia (41% vs 53% for the topotecan arm), thrombocytopenia (21% vs 54%), anemia (16% vs 30%), infections (16% vs 10%), febrile neutropenia (10% vs 4%), all P<0.05, and cardiac disorders (5% vs 5%; P=0.84).
Regulatory status
Amrubicin is currently approved and marketed in Japan for the treatment of small cell lung cancer by Nippon Kayaku, a Japanese pharmaceutical firm focused on oncology, which licensed Japanese marketing rights from Dainippon Sumitomo Pharmaceuticals, the original developer of the therapy. Dainippon Sumitomo Pharmaceuticals also licensed the U.S. and European rights of Amrubicin to Pharmion Corporation, which was acquired by Celgene Corporation in 2008.
For more information:
– Von Pawel J, Jotte R, Spigel D.R. Socinski M.A., O’Brien M.E.R, et al. Randomized phase 3 trial of amrubicin versus topotecan as second-line treatment for small cell lung cancer (SCLC). Abstract 2219
– O’Brien ME, Konopa K, Lorigan P, Bosquee L, Marshall E, et al. Randomised phase II study of amrubicin as single agent or in combination with cisplatin versus cisplatin etoposide as first-line treatment in patients with extensive stage small cell lung cancer – EORTC 08062. Eur J Cancer. 2011 Jun 16. [Epub ahead of print]
– Schmittel A. Second-line therapy for small-cell lung cancer. Expert Rev Anticancer Ther. 2011 Apr;11(4):631-7.
– Kalemkerian GP. Advances in the treatment of small-cell lung cancer. Semin Respir Crit Care Med. 2011 Feb;32(1):94-101. Epub 2011 Apr 15.
– Kimura T, Kudoh S, Hirata K. Review of the management of relapsed small-cell lung cancer with amrubicin hydrochloride. Clin Med Insights Oncol. 2011 Mar 3;5:23-34.
– Nogami N, Hotta K, Kuyama S, Kiura K, Takigawa N, Chikamori K, et al. A phase II study of amrubicin and topotecan combination therapy in patients with relapsed or extensive-disease small-cell lung cancer: Okayama Lung Cancer Study Group Trial 0401. Lung Cancer. 2011 Feb 17. [Epub ahead of print]
Clinical trials:
Phase 3 Trial in Patients With Small Cell Lung Cancer After Failure of First-Line Chemotherapy [NCT00547651]
