Amrubicin active in refractory small-cell lung cancer

The synthetic anthracycline amrubicin conferred a good overall response rate with acceptable safety in a phase-2 trial of platinum-refractory small-cell lung cancer patients.

“Refractory patients have the worse prognosis, with survival of three to five months and overall response rates [ORRs] to second-line chemotherapy of approximately 10%,” the researchers wrote. The study enrolled 75 patients with either progressive disease as best response or with progression within 90 days of first-line therapy. Sixty-nine patients received treatment, with a median of four amrubicin cycles of 40 mg/m² per day for three days every 21 days.

Sixteen patients, or 21.3%, achieved either a complete response (1.3%) or a partial response (20%); 39 patients had either a response or stable disease after 12 weeks. The median OS was six months, and the median PFS was 3.2 months. The OS rates at six months and one year were 48% and 15.7%, respectively.

Adverse events of grade 3 or worse occurred in 92.8% of patients, with neutropenia (66.7%) and thrombocytopenia (40.6%) identified as the most common. The investigators noted that most grade-3 or -4 events occurred during the first or second amrubicin cycle, and then decreased during subsequent cycles. There was also no indication of any anthracycline-induced cardiotoxicity.

“In the refractory SCLC setting, responses to second-line chemotherapy are rare,” the researchers wrote. “Amrubicin is a promising new topoisomerase II inhibitor that is active and has a manageable safety profile.” A phase-3 trial comparing amrubicin with the topoisomerase I inhibitor topotecan (Hytamcin, GlaxoSmithKline) is ongoing.

Ettinger DS. J Clin Oncol. 2010:10.1200;JCO.2009.26.7682.