Phase II multicenter trial of voreloxin as second-line therapy in chemotherapy-sensitive or refractory small cell lung cancer
| Autor: | Tony Reiman, Lee M. Krug, Geoffrey I. Shapiro, Jeffrey Crawford, Daniel C. Adelman, David R. Spigel, Glenn Michelson, Donald Y. Young, Jennifer S. Temel, Ute Hoch, David S. Ettinger |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Oncology
Pulmonary and Respiratory Medicine Male medicine.medical_specialty Quinolone Lung Neoplasms medicine.medical_treatment Pharmacology Neutropenia Refractory Multicenter trial Internal medicine medicine Clinical endpoint Humans Naphthyridines Voreloxin Etoposide Neoplasm Staging Salvage Therapy Chemotherapy biology Small cell lung cancer business.industry Topoisomerase Middle Aged medicine.disease Chemotherapy regimen Small Cell Lung Carcinoma Phase II respiratory tract diseases Survival Rate Thiazoles Treatment Outcome Drug Resistance Neoplasm biology.protein Female business medicine.drug Follow-Up Studies |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 6(2) |
| ISSN: | 1556-1380 |
| Popis: | 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 2 ) 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 2 in a 3-week schedule. |
| Databáze: | OpenAIRE |
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