Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402.
OBJECTIVE
Amrubicin, a new anthracycline agent, and topotecan are both active for previously treated small-cell lung cancer (SCLC). No comparative study of these agents has been reported. This randomized phase II study was conducted to select amrubicin or topotecan for future evaluation.


METHODS
Patients with SCLC previously treated with platinum-containing chemotherapy were randomly assigned to receive amrubicin (40 mg/m(2) on days 1 through 3) or topotecan (1.0 mg/m(2) on days 1 through 5). Patients were stratified by Eastern Cooperative Oncology Group performance status (0, 1, or 2) and type of relapse (chemotherapy sensitive or refractory). The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival, and toxicity profile.


RESULTS
From February 2004 to July 2007, 60 patients were enrolled, and 59 patients (36 patients with sensitive and 23 patients with refractory relapse) were assessable for efficacy and safety evaluation. Neutropenia was severe, and one treatment-related death owing to infection was observed in the amrubicin arm. ORRs were 38% (95% CI, 20% to 56%) for the amrubicin arm and 13% (95% CI, 1% to 25%) for the topotecan arm. In sensitive relapse, ORRs were 53% for the amrubicin arm and 21% for the topotecan arm. In refractory relapse, ORRs were 17% for the amrubicin arm and 0% for the topotecan arm. Median PFS was 3.5 months for patients in the amrubicin arm and 2.2 months for patients in the topotecan arm. Multivariate analysis revealed that amrubicin has more influence than topotecan on overall survival.


CONCLUSIONS
Amrubicin may be superior to topotecan with acceptable toxicity for previously treated patients with SCLC. Further evaluation of amrubicin for relapsed SCLC is warranted.
Department of Respiratory Medicine, Sendai Kousei Hospital, Sendai, Japan. akinoue@idac.tohoku.ac.jp
Akira
A
Inoue
Shunichi
S
Sugawara
Koichi
K
Yamazaki
Makoto
M
Maemondo
Toshiro
T
Suzuki
Kazunori
K
Gomi
Shingo
S
Takanashi
Chieko
C
Inoue
Minoru
M
Inage
Hiroshi
H
Yokouchi
Hiroshi
H
Watanabe
Toumei
T
Tsukamoto
Yasuo
Y
Saijo
Osamu
O
Ishimoto
Fumihiro
F
Hommura
Toshihiro
T
Nukiwa
D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*
D018943:Anthracyclines; D019772:Topotecan; C055866:amrubicin