Phase II multicenter trial of voreloxin as second-line therapy in chemotherapy-sensitive or refractory small cell lung cancer.
BACKGROUND
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.


CONCLUSIONS
Voreloxin has minimal activity in relapsed SCLC when administered at 48 mg/m in a 3-week schedule.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York City, New York, USA. krugl@mskcc.org
Lee M
LM
Krug
Jeffrey
J
Crawford
David S
DS
Ettinger
Geoffrey I
GI
Shapiro
David
D
Spigel
Tony
T
Reiman
Jennifer S
JS
Temel
Glenn C
GC
Michelson
Donald Y
DY
Young
Ute
U
Hoch
Daniel C
DC
Adelman
D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000627:therapeutic use*; D009367:Neoplasm Staging; D016879:Salvage Therapy; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D009287:Naphthyridines; D013844:Thiazoles; C485113:vosaroxin