title: A dose escalation study of topotecan in combination with epirubicin in pretreated patients with small-cell lung cancer.
abstract: OBJECTIVE
  To define the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of topotecan in combination with epirubicin in pretreated patients with small-cell lung cancer (SCLC).
  
  
  METHODS
  Twenty-seven SCLC patients with performance status (WHO) of 0-2 and adequate renal, hepatic, and bone marrow function who had failed EP-containing front-line chemotherapy entered the study. Patients received escalated doses of topotecan (starting dose 0.5 mg/m(2)) for 5 days and epirubicin (starting dose 40 mg/m(2)) on day 8, every 28 days.
  
  
  RESULTS
  All patients were assessable for toxicity and 20 for response. The MTD was topotecan 0.90 mg/m(2) and epirubicin 40 mg/m(2) with neutropenia being the most common dose-limiting event. Seventy-three courses were administered. Grade 3-4 neutropenia occurred in 22 (30%) courses, grade 3-4 anemia in 7 (10%), and grade 3-4 thrombocytopenia in 11 (15%). Seven courses were complicated with fever and one patient died of neutropenic sepsis. Grade 3-4 non-hematologic toxicity was mild and infrequent with only grade 2-3 asthenia occurring in 16 (22%) courses. Among 20 patients who were evaluable for response, 16 (80%) were refractory to prior treatment. One patient with refractory disease (5%) achieved a complete response of 14 weeks duration and four experienced stabilization of the disease.
  
  
  CONCLUSIONS
  The combination of topotecan 0.90 mg/m(2) on days 1-5, with epirubicin 40 mg/m(2) on day 8, administered every 28 days is a feasible outpatient regimen which merits further evaluation in patients with chemosensitive disease.
authors.affiliation: Department of Medical Oncology, University General Hospital of Herakijon, Crete, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Agelaki
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: P
authors.initials: P
authors.lastname: Palamidas
authors.forename: C
authors.initials: C
authors.lastname: Kouroussis
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: K
authors.initials: K
authors.lastname: Kalbakis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: A
authors.initials: A
authors.lastname: Raptis
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D015251:Epirubicin; D019772:Topotecan