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

Abstract

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: Lee M Krug, Jeffrey Crawford, David S Ettinger, Geoffrey I Shapiro, David Spigel, Tony Reiman, Jennifer S Temel, Glenn C Michelson, Donald Y Young, Ute Hoch, Daniel C Adelman
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 6 Issue 2 Pg. 384-6 (Feb 2011) ISSN: 1556-1380 [Electronic] United States
• PMID: 21252718 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Naphthyridines
• Thiazoles
• vosaroxin

Topics

• Drug Resistance, Neoplasm (drug effects)
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Naphthyridines (therapeutic use)
• Neoplasm Staging
• Salvage Therapy
• Small Cell Lung Carcinoma (drug therapy, pathology)
• Survival Rate
• Thiazoles (therapeutic use)
• Treatment Outcome