title: Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed "sensitive" small cell lung cancer.
abstract: Relapsed small cell lung cancer (SCLC) carries a poor prognosis. Topoisomerase I and II inhibitors and DNA-damaging agents are considered among the most active agents against SCLC. Rebeccamycin analog (RA, Becatecarin) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. We performed a phase-II trial of RA in relapsed, sensitive SCLC with the primary end point of response rate. Patients with previously treated SCLC who relapsed more than 60 days after the completion of first-line chemotherapy were treated with RA-administered intravenously at a dose of 140 mg/m on days 1 to 5 of 21-day cycles for a maximum of six cycles. Eligibility included Eastern Cooperative Oncology Group performance status 0 to 2 and adequate organ function. A two-stage design was employed. Twenty evaluable patients were enrolled. Median age was 61 years. Two patients (10%) had a partial response and six had stable disease. The clinical benefit rate was 40% (95% confidence interval [CI], 23-64%). The median progression-free survival was 2 months (95% CI, 1.2-5.2 months). The median survival was 6.7 months (95% CI, 3.3-8.0 months). No treatment-related deaths occurred. Grade-4 neutropenia and thrombocytopenia occurred in 23% and 14% of the patients, respectively. In conclusion, RA has single-agent activity in relapsed, sensitive SCLC with manageable toxicities but is unlikely to provide any superiority compared to existing agents for this disease.
authors.affiliation: Division of Hematology and Oncology, University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Schwandt
authors.forename: Tarek
authors.initials: T
authors.lastname: Mekhail
authors.forename: Balazs
authors.initials: B
authors.lastname: Halmos
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Ma
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D059004:Topoisomerase I Inhibitors / Q000627:therapeutic use*; D059005:Topoisomerase II Inhibitors / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C053339:rebeccamycin