Amrubicin for relapsed small-cell lung cancer: a systematic review and meta-analysis of 803 patients

Abstract

Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57–69%, I2 = 53%), 28% (95% CI 21–35%, I2 = 71%), and 10% (95% CI 6–14%, I2 = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61–78%, I2 = 83%), 36% (95% CI 28–44%, I2 = 80%), and 15% (95% CI 8–21%, I2 = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.

Amphiregulin as a Novel Resistance Factor for Amrubicin in Lung Cancer Cells

“…Comprehensive expression analyses showed that AREG was a direct target of Ser46 phosphorylated p53 (19). In contrast, AMR is a synthetic anthracycline derivative anticancer agent that inhibits DNA topoisomerase II (6). Therefore, we inferred that AMR causes DNA damage and consequently up-regulates the expression of AREG via Ser46-phosphorylated p53.…”

“…Previous studies have suggested that AMR may be a good choice for treating lung cancer, especially relapsed SCLC (6). A phase III study of AMR as a second-line treatment for SCLC showed overall response rates of approximately 30%.…”

Efficacy and safety of amrubicin‐based regimen used as first‐line for extensive‐disease small‐cell lung cancer: A meta‐analysis of randomized controlled trials

“…There has been one published systematic review and meta‐analysis, which evaluated the efficacy and safety of amrubicin as second‐ or third‐line chemotherapy for patients with relapsed SCLC . In that study, the authors included five single‐arm studies and four RCTs.…”

“…In that study, the authors included five single‐arm studies and four RCTs. Of the four RCTs, three compared amrubicin with topotecan and the remaining one compared amrubicin with rechallenge with platinum doublet . They found that the 3‐, 6‐, and 9‐month PFS for amrubicin was 63%, 28%, and 10%, respectively; the 6‐, 12‐, and 18‐month OS was 69%, 36%, and 15%, respectively .…”

The efficacy of amrubicin third‐line chemotherapy in patients with relapsed extensive‐disease small‐cell lung cancer: A retrospective and historical study in a single institute

“…In clinical trials, amrubicin is associated with an equivalent median survival time to topotecan for sensitive SCLC and with improved OS compared to topotecan for refractory SCLC (6.2 months vs. 5.7 months, respectively; P = 0.047) . In addition, in a systematic review and meta‐analysis of 803 patients who received second‐line amrubicin, amrubicin was associated with better OS for refractory‐relapsed cases compared with topotecan . Based on these clinical studies, the 2014 Japanese lung cancer guidelines recommended amrubicin as an optional agent for second‐line chemotherapy for ED‐SCLC in Japan.…”