title: Randomized phase II trial of different schedules of administration of rebeccamycin analogue as second line therapy in non-small cell lung cancer.
abstract: Rebeccamcyin analogue (RA) is an antitumor antibiotic that results in DNA intercalation and topoisomerase I and II inhibition. Phase I trials of the daily x 5 schedule and once every 3 week schedule have been completed. Antitumor activity was observed during the phase I trials. The purpose of this study is to primarily determine the response rate of 2 different schedules of administration of RA in patients with advanced non-small cell lung cancer (NSCLC) who had progressed on one prior chemotherapy regimen. Secondary endpoints were median and 1-year survival rates. A two-stage Simon design was employed for both arms of the study. Patients were randomly assigned to either of two RA treatment schedules of 500 mg/m(2) as a 1 hr infusion repeated every 3 weeks (Arm A) or 140 mg/m(2)/day x 5 days repeated every 3 weeks (Arm B). Forty-two patients were randomized. No confirmed objective responses were seen. Stable disease was seen in 52% of patients on arm A and 37% on arm B. Median survival and 1 year survival rates were 5.6 months and 33.3% for arm A, 9.7 months and 42.1% for arm B respectively. Cox regression model demonstrated increased risk of death in patients younger than the age of 61 and for patients treated on arm A. RA failed to demonstrate a significant response rate in this disease setting, although the proportion of patients with stable disease and 1-year survival were encouraging and similar to other published studies of approved single agents for second-line therapy of NSCLC.
authors: Developmental Therapeutics Program, CASE Comprehensive Cancer Center and the Division of Hematology/Oncology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA. afshin.dowlati@case.edu
authors: Afshin
authors: A
authors: Dowlati
authors: Robert
authors: R
authors: Chapman
authors: Shanmuga
authors: S
authors: Subbiah
authors: Pingfu
authors: P
authors: Fu
authors: Anne
authors: A
authors: Ness
authors: Tania
authors: T
authors: Cortas
authors: Lauren
authors: L
authors: Patrick
authors: Sherrie
authors: S
authors: Reynolds
authors: Natalie
authors: N
authors: Xu
authors: Nathan
authors: N
authors: Levitan
authors: Percy
authors: P
authors: Ivy
authors: Scot C
authors: SC
authors: Remick
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002227:Carbazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D007211:Indoles; C053339:rebeccamycin