title: Combined therapy with topotecan and gemcitabine in patients with inoperable or metastatic non-small cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I/II trial of topotecan combined with gemcitabine in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) based on preclinical data showing in vitro synergy against an established lung adenocarcinoma cell line. The aim was to determine the maximally tolerated dose (MTD) of topotecan when the gemcitabine dose is held constant, as well the dose limiting toxicity (DLTs) of this combination in NSCLC patients.
  
  
  METHODS
  Twenty-four patients with stage IIIB or IV NSCLC were treated weekly times 3 with a week break with gemcitabine (1250 mg/m2 over 30 minutes) and topotecan (30 minutes) at varying doses. The starting dose of topotecan was 1.0 mg/m2 and doses were escalated in 0.25-mg/m2 increments until the MTD was achieved.
  
  
  RESULTS
  The MTD of gemcitabine/topotecan was 1250 mg/m2 of gemcitabine and 2.00 mg/m2 of topotecan (level 5). Neutropenia was the DLT. Few nonhematologic toxicities were observed. There were 5 (21%) partial responses among 24 patients. The median survival was 22 weeks. Two patients have had prolonged (> 2 year) survival.
  
  
  CONCLUSIONS
  The combination of gemcitabine and topotecan seems to be active against NSCLC with acceptable hematologic toxicity and minimal nonhematologic toxicity. The recommended dose for further study is 1250 mg/m2 of gemcitabine (days 1, 8, 15) and 2.0 mg/m2 of topotecan (days 1, 8, 15) administered every 28 days.
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania, USA. dabrowmb@pearl.umdnj.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Dabrow
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Francesco
authors.forename: Paul B
authors.initials: PB
authors.lastname: Gilman
authors.forename: Ronald
authors.initials: R
authors.lastname: Cantor
authors.forename: Lewis
authors.initials: L
authors.lastname: Rose
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meyer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D019772:Topotecan; D000093542:Gemcitabine