Grade-3 febrile neutropenia developed in 22 patients (26.8%). Nonhematological toxicities were generally mild and no evidence of cardiotoxicity of AMR was found in this study (Table 4). Pneumonitis was observed in nine patients (grade 4, n = 1; grade 3, n = 2; grade 2, n = 3; selleck chemical and grade 1, n = 3), and seven (grade 4, n = 1; grade 3, n = 2; grade 2, n = 2; and grade 1, n = 2) discontinued treatment because of unacceptable toxicity levels. The incidence rate of pneumonitis was higher in patients with history of thoracic radiation therapy than in others (38.5% v 5.8%, respectively), but one grade 4 pneumonitis case was observed in a patient without a history of thoracic radiation therapy. G-CSF was

administered to 51 (62.2%) patients and blood transfusions were necessary in 9 (11.0%). No treatment-related death was observed in this GKT137831 study. This single-arm confirmatory study was conducted to confirm the efficacy and safety of AMR in patients with refractory SCLC. In the present study, the primary endpoint was the ORR, which was 32.9%. This data supported the result that the ORR of AMR therapy was significantly better than that of topotecan therapy, in accordance with that previously reported in a randomized phase II study by Inoue et al. [9]. A possible limitation

of this study is related to its design, which was not a randomized phase III study, but rather a nonrandomized single-arm confirmatory study. Although there was potential for selection bias as a result of this study design, ORR was sufficiently higher than that for topotecan therapy in previous studies [8] and [11]. The secondary endpoints, PFS and OS, were also favorable, and Fenbendazole no

treatment-related deaths occurred in this study. On the basis of these results, we conclude that AMR monotherapy is suitable as an effective and safe treatment option for refractory SCLC. Jotte et al. [15] reported the results of a randomized phase III trial of AMR versus topotecan as second-line treatment for SCLC. The study randomized 637 patients in a 2:1 ratio for treatment with AMR (n = 424) or topotecan (n = 213). Treatment with AMR and topotecan showed similar OS periods (median, 7.5 v 7.8 months; hazard ratio for death, 0.880; 95% CI, 0.733–1.057; P = 0.17); however, higher ORRs (31.1% v 16.9%; P = 0.0001) and PFS periods (median, 4.1 v 3.5 months; hazard ratio for death or disease progression, 0.802; 95% CI, 0.667–0.965; P = 0.0182) were found with AMR therapy, and toxicity levels were more acceptable than those with topotecan therapy. Furthermore, in a subset analysis of 295 patients with refractory SCLC, AMR therapy demonstrated a modest improvement in OS (median, 6.2 v 5.7 months; hazard ratio for death, 0.766; 95% CI, 0.589–0.997; P = 0.0469). These results support our assertion that AMR monotherapy is a reasonable treatment option for patients with refractory SCLC.