Phase II study of amrubicin at a dose of 45 mg/m²in patients with previously treated small-cell lung cancer

Abstract

Objective: Most of the previous studies of amrubicin in patients with previously treated small-cell lung cancer were conducted at a dose of 40 mg/m 2 . The aim of this study was to assess the efficacy and safety of amrubicin at a dose of 45 mg/m 2 in patients with relapsed or refractory small-cell lung cancer.Methods: Previously treated small-cell lung cancer patients were eligible. Amrubicin at a dose of 45 mg/m 2 was administered on Days 1-3 every 3 weeks. The primary endpoint was the response rate.Results: From June 2003 to January 2005, 35 patients were enrolled, of whom 34 received this study treatment. Four cycles or more could be administered in 21 patients (62%). Dose reduction was required in 15 (52%) of the 29 patients who had received two cycles or more. Three complete responses and 15 partial responses were observed among the 34 treated patients, yielding a response rate of 53% (95% confidence interval, 35-71%). Median progression-free survival of the patients was 4.4 months (95% confidence interval, 2.4-5.1 months). Median survival time was 8.2 months (95% confidence interval, 6.6-10.0 months) and 1-year survival rate was 24% (95% confidence interval, 9-39%). Grade 3/4 leukopenia, neutropenia and thrombocytopenia were observed in 76, 97 and 38% of the patients, respectively. Febrile neutropenia occurred in 12 patients (35%), and one patient died from pneumonia. Conclusions: While amrubicin at a dose of 45 mg/m 2 showed high response rate for both sensitive and refractory relapse, the incidence of febrile neutropenia was also high. The utility of amrubicin at 45 mg/m 2 might accordingly be limited.

Amrubicin monotherapy for elderly patients with relapsed extensive‐disease small‐cell lung cancer: A retrospective study

“…Previous studies found that an AMR dose of 40 mg/m 2 showed adequate activity and acceptable toxicity in previously treated SCLC patients . Meanwhile, an AMR dose of 45 mg/m 2 , while effective, produced intolerable toxicities and even treatment‐related deaths in other studies . Sekine et al .…”

“…[13][14][15][16]20,21 Meanwhile, an AMR dose of 45 mg/m 2 , while effective, produced intolerable toxicities and even treatment-related deaths in other studies. 22,23 Sekine et al conducted a valuable randomized phase III study that showed that higher incidences of febrile neutropenia and interstitial lung disease of grade 3 or worse occurred with 45 mg/m 2 AMR; they concluded that AMR at 45 mg/m 2 is toxic and intolerable in chemonaïve elderly Japanese patients with ED-SCLC. 24 These findings show that the AMR dose is critical for avoiding fatal adverse events, such as severe neutropenia or febrile neutropenia.…”

Comparison of carboplatin plus etoposide with amrubicin monotherapy for extensive‐disease small cell lung cancer in the elderly and patients with poor performance status

“…Another study found that amrubicin was efficacious against relapsed ED‐SCLC at 35–40 mg/m 2 . However, administration of amrubicin at 45 mg/m 2 , while effective, produced intolerable toxicities and even treatment‐related deaths in separate studies . Thus, the amrubicin dose is critical to avoid severe or febrile neutropenia.…”

<p>Impact of Amrubicin Monotherapy as Second-Line Chemotherapy on Outcomes in Elderly Patients with Relapsed Extensive-Disease Small-Cell Lung Cancer</p>

“…Meanwhile, although an AMR dose of 45 mg/m 2 was reportedly effective, it produced intolerable toxicities and even treatment-related deaths in other studies. 48,49 Furthermore, a randomized phase III study previously reported by Sekine et al indicated that higher incidences of febrile neutropenia and interstitial lung disease of grade 3 or worse occurred with 45 mg/m 2 AMR; the authors concluded that AMR at 45 mg/m 2 is intolerable in chemo-naïve elderly Japanese patients with ED-SCLC. 27 These findings demonstrate that the appropriate AMR dose is critical for avoiding fatal adverse events, such as severe neutropenia or febrile neutropenia.…”