title: A dose-escalation study of weekly topotecan, cisplatin, and gemcitabine front-line therapy in patients with inoperable non-small cell lung cancer.
abstract: OBJECTIVE
  To determine the optimal dose of combination topotecan, cisplatin, and gemcitabine in advanced non-small cell lung cancer patients.
  
  
  METHODS
  This single-center, single-practice, phase I trial enrolled chemotherapy-naïve patients with inoperable stage IIIB/IV disease. Initial treatment was topotecan (0.5-2.0 mg/m(2)), cisplatin (20 mg/m(2)), and gemcitabine (1,000 mg/m(2)) on days 1, 8, and 15 of a 28-day cycle. Dose-limiting thrombocytopenia at week 3 necessitated less frequent gemcitabine dosing (days 1 and 15 of each cycle). Thereafter, topotecan dose escalation proceeded to the target dose of 2 mg/m(2).
  
  
  RESULTS
  Thirty patients were enrolled and evaluable for toxicity assessment. Treatment was extremely well tolerated: only one grade 4 adverse event (leukopenia); no hospitalizations for treatment-related toxicities; no fever/neutropenia. Although no dose-limiting toxicities developed, 1.75 mg/m(2) topotecan is considered optimal and recommended for further study because it was well tolerated, active, and did not require dose adjustments or delays in therapy. Eleven of 29 (38%) evaluable patients achieved a partial response. Median survival was 38 weeks (range 4-110 weeks), median progression-free survival was 17 weeks, and the 1-year survival rate was 33%. Two patients remain alive after 108-122 weeks of follow-up.
  
  
  CONCLUSIONS
  A 28-day cycle of topotecan (1.75 mg/m(2) days 1, 8, 15), cisplatin (20 mg/m(2) days 1, 8, 15), and gemcitabine (1,000 mg/m(2) days 1, 15) was a safe and well-tolerated outpatient treatment for advanced non-small cell lung cancer. The favorable preliminary efficacy and safety of this regimen suggest that further study in phase II trials, including quality-of-life end points, is warranted.
authors.affiliation: Medical Oncology Hematology Consultants, PA, Christiana Care Health System, Helen F. Graham Cancer Center, 4701 Ogletown-Stanton Road, Suite 2200, Wilmington, DE 19713, USA. mguarino@magpage.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Guarino
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Schneider
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Grubbs
authors.forename: David D
authors.initials: DD
authors.lastname: Biggs
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Himelstein
authors.forename: Kurt
authors.initials: K
authors.lastname: Hogaboom
authors.forename: Samir
authors.initials: S
authors.lastname: Tilak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D019772:Topotecan; D002945:Cisplatin; D000093542:Gemcitabine