title: Phase I dose escalation study of vinorelbine and topotecan combination chemotherapy in patients with recurrent lung cancer.
abstract: BACKGROUND
  A platinum doublet is the current standard treatment for good performance status patients with advanced non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC) with good performance status. However, platinum-based treatment may be associated with significant toxicities, therefore alternative platinum-free combinations should be investigated. Topotecan is a topoisomerase I inhibitor that exerts its cytotoxic effect through stabilization of the topoisomerase I-DNA complex. Preclinical data suggests synergy between topoisomerase I inhibitors and mitotic spindle poisons. Considerable hematologic toxicities have been reported with topotecan dosed for 5 consecutive days in combination with vinorelbine. Therefore, the aim of this study was to evaluate the optimal dosage and the maximal tolerated dose (MTD) of topotecan and vinorelbine in patients with relapsed or refractory non-small cell or small cell lung cancer administered on an alternate dosing schedule.
  
  
  METHODS
  From February, 2004 to March, 2007 eighteen patients with advanced or recurrent NSCLC or SCLC previously treated with chemotherapy were enrolled. Patients were heavily pretreated with 22% having received at least 3 prior lines of chemotherapy. Vinorelbine was administered at a fixed dose (20 mg/m2) and topotecan at escalating doses (2, 2.5, 3, 3.5, and 4 mg/m2) on days 1 and 8 every 21 days.
  
  
  RESULTS
  The MTD was not reached in any of the 5 cohorts, with only one dose limiting toxicity (DLT) occurring in cohort 4. Non-hematological toxicities were manageable. One patient had a partial response with four patients (27%) achieving stable disease. The median progression-free and overall survival for all patients, were 2.7 months (95% CI: 1.6, 9.1) and 10.5 months (95% CI: 4.2, 22.7), respectively.
  
  
  CONCLUSIONS
  Vinorelbine and topotecan administered on days 1 and 8 every 21 days is well tolerated without any DLT seen with previously investigated topotecan schedules. This doublet provides a potentially active non-platinum containing doublet for the treatment of patients with advanced SCLC and NSCLC. Vinorelbine and topotecan should therefore be investigated in subsequent phase II studies at a dose of 20 mg/m2 and 4 mg/m2, respectively.
  
  
  BACKGROUND
  NCT00287963.
authors: Division of Medical Oncology/Hematology, Hollings Cancer Center, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. beldner@musc.edu
authors: Matthew A
authors: MA
authors: Beldner
authors: Carol A
authors: CA
authors: Sherman
authors: Mark R
authors: MR
authors: Green
authors: Elizabeth
authors: E
authors: Garrett-Mayer
authors: Uzair
authors: U
authors: Chaudhary
authors: Mario L
authors: ML
authors: Meyer
authors: Andrew S
authors: AS
authors: Kraft
authors: Alberto J
authors: AJ
authors: Montero
mesh_terms: D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D019772:Topotecan / Q000008:administration & dosage*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D019772:Topotecan; D000077235:Vinorelbine