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Updated: Jun 5, 2026
Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
Published on: October 2, 2014
Phase II multicenter trial of voreloxin as second-line therapy in chemotherapy-sensitive or refractory small cell
Lee M Krug1, Jeffrey Crawford, David S Ettinger
1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York City, New York, USA. krugl@mskcc.org
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.
Insights
Voreloxin showed minimal activity as a second-line treatment for relapsed small cell lung cancer (SCLC). The drug resulted in an 11% response rate in sensitive SCLC but no response in refractory SCLC.
Area of Science:
- Oncology
- Pharmacology
Background:
- Voreloxin, a quinolone derivative, targets DNA intercalation and topoisomerase II inhibition.
- Preclinical data suggested efficacy in chemoresistant tumors and early phase I activity.
- Its mechanism is similar to established topoisomerase II inhibitors like anthracyclines and etoposide.
Purpose of the Study:
- To evaluate voreloxin as a second-line treatment for extensive-stage small cell lung cancer (SCLC).
- To assess response rates in chemotherapy-sensitive and chemotherapy-refractory SCLC cohorts.
Main Methods:
- A Phase II trial enrolled patients with extensive-stage SCLC previously treated with one chemotherapy regimen.
- Patients were stratified into sensitive or refractory disease cohorts.
- Voreloxin was administered at 48 mg/m every 21 days for up to six cycles, with objective response rate as the primary endpoint.
Main Results:
- Of 47 evaluable patients, three (11% response rate) in the sensitive SCLC cohort achieved an objective response (1 complete, 2 partial).
- No responses were observed in the chemotherapy-refractory SCLC cohort.
- The primary toxicity observed was neutropenia.
Conclusions:
- Voreloxin demonstrated minimal activity in relapsed SCLC at the tested dose and schedule.
- The drug's efficacy appears limited in both sensitive and refractory settings for this indication.
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