INTRODUCTION: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Voreloxin has minimal activity in relapsed SCLC when administered at 48 mg/m in a 3-week schedule.
INTRODUCTION: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). METHODS: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. RESULTS: 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. CONCLUSION:Voreloxin has minimal activity in relapsed SCLC when administered at 48 mg/m in a 3-week schedule.
Authors: Elizabeth A Williamson; Leah Damiani; Andrei Leitao; Chelin Hu; Helen Hathaway; Tudor Oprea; Larry Sklar; Montaser Shaheen; Julie Bauman; Wei Wang; Jac A Nickoloff; Suk-Hee Lee; Robert Hromas Journal: Cancer Res Date: 2012-10-22 Impact factor: 12.701
Authors: Primo N Lara; James Moon; Mary W Redman; Thomas J Semrad; Karen Kelly; Jeffrey W Allen; Barbara J Gitlitz; Philip C Mack; David R Gandara Journal: J Thorac Oncol Date: 2015-01 Impact factor: 15.609
Authors: Peter M Bruno; Mengrou Lu; Kady A Dennis; Haider Inam; Connor J Moore; John Sheehe; Stephen J Elledge; Michael T Hemann; Justin R Pritchard Journal: Proc Natl Acad Sci U S A Date: 2020-02-10 Impact factor: 11.205