title: A phase II study of higher dose weekly topotecan in relapsed small-cell lung cancer.
abstract: BACKGROUND
  Five-day topotecan is approved by the US Federal Drug Administration (FDA) for sensitive relapsed small-cell lung cancer (SCLC). We previously found that 4 mg/m(2) intravenous (I.V.) weekly dosing resulted in low-grade 3/4 toxicity but an overall response rate (ORR) < 10%. We hypothesized that higher topotecan dosing could improve ORR without significantly increasing toxicity.
  
  
  METHODS
  This multicenter phase II trial sought a 25% ORR (α = 0.04; β = 0.20). Eligible patients (sensitive or refractory relapsed SCLC; Eastern Cooperative Oncology Group [ECOG] performance status [PS] 0-1; measurable disease) received weekly topotecan (6 mg/m(2) I.V. for 6 weeks) and were restaged every 8 weeks.
  
  
  RESULTS
  Baseline characteristics were N = 38, enrolled 5/2006-10/2007; median age 64 years (range, 35-82), 47% female, 74% ECOG PS 1, 50% refractory relapsed SCLC. The median follow-up was 15 months (range, 12-24 months). No patients received all planned therapy; only 1 patient was able to receive all planned treatment in cycle 1 because of hematologic toxicity and progressive disease (PD). Among all patients, ORR was 8% (95% confidence interval [CI], 2%-21%), 24% had stable disease, and disease in 47% progressed. Among sensitive relapsed patients ORR was 16% (95% CI, 3%-40%) with no complete responses; median response duration was 3.3 months. Five (26%) patients had stable disease; 8 (42%) patients had PD. Among sensitive relapsed patients, the median time to progression (TTP) and overall survival (OS) was 2.5 months and 8.6 months, respectively. Among refractory relapsed patients there were no ORRs, and median TTP and OS were 1.5 months and 3.7 months, respectively. Grade 3/4 toxicities (> 10%) included neutropenia (53%), leukopenia (42%), thrombocytopenia (37%), anemia (13%), fatigue (13%), and pain (13%). There were no treatment-related deaths.
  
  
  CONCLUSIONS
  Weekly topotecan (6 mg/m(2) I.V.) is not feasible because of hematologic toxicity and does not improve efficacy in patients with relapsed SCLC.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA. dspigel@tnonc.com
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Shipley
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Clark
authors.forename: Robert C
authors.initials: RC
authors.lastname: Whorf
authors.forename: Edward R
authors.initials: ER
authors.lastname: Arrowsmith
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; 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 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D059004:Topoisomerase I Inhibitors; D019772:Topotecan