title: A phase I clinical trial of weekly oral topotecan for relapsed small cell lung cancer.
abstract: OBJECTIVE
  To determine the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of oral topotecan administered weekly in patients with relapsed small cell lung cancer (SCLC).
  
  
  METHODS
  Patients were treated with oral topotecan on days 1, 8, and 15, every 28 days. The dose was escalated by 0.5 mg/m² increments from the starting dose of 3 mg/m² until the MTD was reached. DLTs were defined as grade 4 neutropenia, febrile neutropenia, grade 4 thrombocytopenia, non-hematologic toxicity ≥grade 3, any toxicity precluding the treatment on days 8 or 15 of the first cycle, or delay of the second cycle for more than 7 days.
  
  
  RESULTS
  Eighteen patients were enrolled. Thirteen patients received oral topotecan as second-line and five as third- or further-line treatment. The DLT level was reached at 4.5 mg/m², and the MTD was determined to be 4 mg/m². DLTs consisted of grade 2/3 neutropenia and grade 2 thrombocytopenia precluding treatment on day 15 of the first cycle or on day 1 of the second cycle. The most frequent toxicities were grade 2-3 neutropenia (27.8 % of patients), grade 2-3 anemia (33.3 %), grade 2 thrombocytopenia (16.7 %), and grade 2-3 fatigue (44.4 %). The response rate was 11.1 %, the median progression-free survival 2.3 months, and the median overall survival 5.1 months.
  
  
  CONCLUSIONS
  The recommended phase II dose of weekly oral topotecan in pretreated patients with SCLC is 4 mg/m² on days 1, 8, and 15 every 28 days.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, 71110, Heraklion, Crete, Greece. agelaki@med.uoc.gr
authors.forename: S
authors.initials: S
authors.lastname: Agelaki
authors.forename: E
authors.initials: E
authors.lastname: Kontopodis
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
authors.forename: V
authors.initials: V
authors.lastname: Chandrinos
authors.forename: I
authors.initials: I
authors.lastname: Bompolaki
authors.forename: Zeta
authors.initials: Z
authors.lastname: Zafeiriou
authors.forename: E
authors.initials: E
authors.lastname: Papadimitraki
authors.forename: D
authors.initials: D
authors.lastname: Stoltidis
authors.forename: K
authors.initials: K
authors.lastname: Kalbakis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009503:Neutropenia / Q000139:chemically induced; D010166:Palliative Care; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D013921:Thrombocytopenia / Q000139:chemically induced; 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