Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy.
OBJECTIVE
This phase II study evaluated the safety and efficacy of single-agent amrubicin versus topotecan in patients with small-cell lung cancer (SCLC) sensitive to first-line platinum-based chemotherapy.


METHODS
Patients were randomly assigned 2:1 to amrubicin (40 mg/m(2)/d in a 5-minute intravenous [IV] infusion, days 1 through 3, every 21 days) or topotecan (1.5 mg/m(2)/d in a 30-minute IV infusion, days 1 through 5, every 21 days). The primary efficacy end point was overall response rate (ORR) for amrubicin. Secondary end points included time to progression, median progression-free survival (PFS), and median overall survival (OS).


RESULTS
Of 76 patients enrolled, 50 patients were randomly assigned to amrubicin, and 26 patients were randomly assigned to topotecan. Amrubicin treatment resulted in a significantly higher ORR than topotecan (44% v 15%; P = .021). Median PFS and median OS were 4.5 months and 9.2 months with amrubicin and 3.3 months and 7.6 months with topotecan, respectively. Tolerability was similar with both agents. However, grade 3 or worse neutropenia and thrombocytopenia seemed to be more frequent in the topotecan group as compared with the amrubicin group (78% and 61% v 61% and 39%, respectively).


CONCLUSIONS
Amrubicin shows promising activity, with an ORR of 44% compared with an ORR of 15% for topotecan as second-line treatment in patients with SCLC sensitive to first-line platinum-based chemotherapy. In addition, the safety profiles were comparable; however, a trend was noted for more frequent grade 3 or worse neutropenia and thrombocytopenia in the topotecan group as compared with the amrubicin group. Additional studies are ongoing.
Rocky Mountain Cancer Centers, 10103 Ridgegate Pkwy G-01, Lone Tree, CO 80124, USA. robert.jotte@usoncology.com
Robert
R
Jotte
Paul
P
Conkling
Craig
C
Reynolds
Matthew D
MD
Galsky
Leonard
L
Klein
James F
JF
Fitzgibbons
Richard
R
McNally
Markus F
MF
Renschler
Jennifer W
JW
Oliver
D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D059004:Topoisomerase I Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States
D018943:Anthracyclines; D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; C055866:amrubicin