Skip to main content
placeholder image

Randomized phase III trial of Amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer

Journal Article


Abstract


  • Purpose: Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC. Patients and Methods: A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m2 intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m2 IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety. Results: Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P < .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ��� 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes. Conclusion: Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin.

UOW Authors


  •   Clingan, Phillip (external author)

Publication Date


  • 2014

Citation


  • Von Pawel, J., Jotte, R., Spigel, D. R., O'Brien, M. E. R., Socinski, M. A., Mezger, J., . . . Renschler, M. F. (2014). Randomized phase III trial of Amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. Journal of Clinical Oncology, 32(35), 4012-4018. doi:10.1200/JCO.2013.54.5392

Scopus Eid


  • 2-s2.0-84918588050

Web Of Science Accession Number


Start Page


  • 4012

End Page


  • 4018

Volume


  • 32

Issue


  • 35

Place Of Publication


Abstract


  • Purpose: Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II trials. This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC. Patients and Methods: A total of 637 patients with refractory or sensitive SCLC were randomly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m2 intravenously (IV) on days 1 to 3 or topotecan 1.5 mg/m2 IV on days 1 to 5. Primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival (PFS), and safety. Results: Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan (HR, 0.802; P < .018). ORR was 31.1% with amrubicin and 16.9% with topotecan (odds ratio, 2.223; P < .001). Grade ��� 3 treatment-emergent adverse events in the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004), thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001), respectively. NQO1 polymorphisms did not influence safety outcomes. Conclusion: Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC. OS did not differ significantly between treatment groups, although an improvement in OS was noted in patients with refractory disease treated with amrubicin.

UOW Authors


  •   Clingan, Phillip (external author)

Publication Date


  • 2014

Citation


  • Von Pawel, J., Jotte, R., Spigel, D. R., O'Brien, M. E. R., Socinski, M. A., Mezger, J., . . . Renschler, M. F. (2014). Randomized phase III trial of Amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. Journal of Clinical Oncology, 32(35), 4012-4018. doi:10.1200/JCO.2013.54.5392

Scopus Eid


  • 2-s2.0-84918588050

Web Of Science Accession Number


Start Page


  • 4012

End Page


  • 4018

Volume


  • 32

Issue


  • 35

Place Of Publication