title: A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer.
abstract: OBJECTIVE
  Topotecan (Hycamtin is active in small-cell lung cancer (SCLC). This phase II study investigated the efficacy and safety of topotecan in combination with either cisplatin or etoposide in untreated extensive disease SCLC (ED SCLC).
  
  
  METHODS
  Patients with untreated ED SCLC were randomised to treatment with T/C (topotecan 1.25mg/(m(2)day) IV days 1-5, cisplatin 50mg/m(2) IV day 5; 41 patients) or T/E (topotecan 0.75 mg/(m(2)day) IV days 1-- 5, etoposide 60 mg/(m(2)day) IV days 1-5; 41 patients) every 21 days. Response was evaluated by strict radiological criteria.
  
  
  RESULTS
  Response rates were similar for T/C (63.4%, 95% CI: 48.7-78.2%) and T/E (61.0%, 95% CI: 46-76%) with one patient in each arm who underwent complete response. Median survival was 41.6 weeks (9.6 months) for the T/C group and 43.7 weeks (10.1 months) for the T/E group. Toxicity was primarily haematological in both groups. The proportion of patients with grades 3-4 anaemia was significantly higher in the T/C arm (46.4%) versus 20% with the T/E arm (p=0.018). The proportion of patients with grade 4 neutropenia was not significantly lower with T/C (56.1%) than with T/E (65.0%, p=0.41), as was the incidence of associated events such as sepsis (T/C: 0%; T/E: 9.8%, p=0.11). The overall deliverability of either regimen was similar. The most frequent non-haematological adverse experiences of all grades per patient were nausea (T/C: 43.9%; T/E: 36.6%), and alopecia (T/C: 39.0%; T/E: 56.1%). Topotecan did not appear to increase the frequency of adverse events specifically associated with cisplatin.
  
  
  CONCLUSIONS
  This study showed T/C and T/E to be effective and well tolerated in patients with ED SCLC and further evaluation of topotecan in first line SCLC is warranted.
authors: Hôpitaux Universitaires, Strasbourg, France. elisabeth.quoix@chru-strasbourg.fr
authors: Elisabeth
authors: E
authors: Quoix
authors: Jean-Luc
authors: JL
authors: Breton
authors: Radj
authors: R
authors: Gervais
authors: Jonathan
authors: J
authors: Wilson
authors: Franz
authors: F
authors: Schramel
authors: Felipe
authors: F
authors: Cardenal
authors: Graham
authors: G
authors: Ross
authors: Alaknanda
authors: A
authors: Preston
authors: Margarita
authors: M
authors: Lymboura
authors: Karin
authors: K
authors: Mattson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin