Phase II Multicenter Trial of Voreloxin as Second-Line Therapy in Chemotherapy-Sensitive or Refractory Small Cell Lung Cancer

Abstract

Voreloxin is an anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, causing double-strand breaks in DNA, irreversible G2 arrest, and rapid onset of apoptosis. Based on preclinical activity of voreloxin in chemoresistant tumors, early phase I clinical activity, and a mechanism of action similar to other topoisomerase II inhibitors such as the anthracyclines and etoposide, this phase II trial was undertaken as second-line treatment of small cell lung cancer (SCLC). Patients with extensive stage SCLC previously treated with one prior chemotherapy regimen were eligible. Patients with chemotherapy-sensitive or chemotherapy-refractory disease were considered as separate cohorts. Voreloxin (48 mg/m) was administered on the first day of each 21-day cycle for up to six cycles. The primary end point was objective response rate. Fifty-five patients were enrolled including 28 with refractory SCLC and 27 with sensitive SCLC; 47 were evaluable for response. Three patients with sensitive SCLC had an objective response, including one complete response and two partial responses (11% response rate based on intent to treat). No patients in the refractory cohort had a response. The primary grade 3 toxicity was neutropenia. Voreloxin has minimal activity in relapsed SCLC when administered at 48 mg/m in a 3-week schedule.