title: Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer.
abstract: OBJECTIVE
  Single-agent intravenous (IV) topotecan is an effective treatment for small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open-label, randomized, phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy.
  
  
  METHODS
  Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status < or = 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of > or = 90 days were assigned to treatment with either oral topotecan 2.3 mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment.
  
  
  RESULTS
  A total of 309 patients were randomly assigned. In intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153) and 21.9% with IV topotecan (n = 151), with a difference (oral -IV) of -3.6% (95% CI, -12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third-line chemotherapy was similar for both groups (33% for oral; 35% for IV). Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3 or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most frequent nonhematologic adverse events (all grades) included nausea (43% oral; 42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea (36% oral; 20% IV).
  
  
  CONCLUSIONS
  Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.
authors.affiliation: Center for Cancer Care and Research, St Louis, MO 63141, USA. jeckardt@tcccr.com
authors.forename: John R
authors.initials: JR
authors.lastname: Eckardt
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pujol
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Papai
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Quoix
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: Ruth
authors.initials: R
authors.lastname: Poulin
authors.forename: Alaknanda J
authors.initials: AJ
authors.lastname: Preston
authors.forename: Graham
authors.initials: G
authors.lastname: Dane
authors.forename: Graham
authors.initials: G
authors.lastname: Ross
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan