title: Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group.
abstract: BACKGROUND
  This trial was designed to compare the efficacy and toxicity of sequential versus alternating administration of cisplatin/etoposide and topotecan in patients with previously untreated extensive-stage small-cell lung cancer (SCLC).
  
  
  METHODS
  Two hundred eighty-four chemotherapy-naive patients were randomized between the sequential therapy arm (n=142; 4 cycles of cisplatin 75 mg/m2 intravenously [I.V.] on day 1 with etoposide 100 mg/m2 per day I.V. on days 1-3 followed by 4 cycles of topotecan 1.5 mg/m2 per day I.V. on days 1-5) and the alternating arm (n=142; same doses of cisplatin/etoposide on cycles 1, 3, 5, and 7 and topotecan on cycles 2, 4, 6, and 8). Treatment cycles for both regimens were administered every 3 weeks.
  
  
  RESULTS
  At this preliminary analysis, no statistically significant difference in the overall response rate, duration of response, time to disease progression, or median survival was observed between the 2 arms. A total of 756 cycles of the sequential therapy and 830 cycles of the alternating therapy were administered, with a median numbers of 6 and 7 cycles per patient, respectively. Topotecan was administered in 85 patients on the sequential arm and 132 patients on the alternating arm. Dose reductions for toxicity were similar in both arms. Grade 3/4 toxicities in the sequential and alternating arms, respectively, included neutropenia (51% and 52%; P=NS), anemia (12% and 11%; P=NS), febrile neutropenia (7% and 9%; P=NS), thrombocytopenia (19% and 20%; P=NS), and asthenia (8% and 2%; P=0.02). There were 4 toxicity-related deaths in the sequential arm versus 3 in the alternating arm.
  
  
  CONCLUSIONS
  Our preliminary conclusion is that the sequential and alternating regimens resulted in comparable activity and tolerability in previously untreated patients with extensive-stage SCLC.
authors.affiliation: Department of Medical Oncology, School of Medicine, University of Crete, Greece.
authors.forename: Michail
authors.initials: M
authors.lastname: Ignatiadis
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.forename: Marinos
authors.initials: M
authors.lastname: Veslemes
authors.forename: John
authors.initials: J
authors.lastname: Boukovinas
authors.forename: Kostas
authors.initials: K
authors.lastname: Syrigos
authors.forename: Maria
authors.initials: M
authors.lastname: Agelidou
authors.forename: Athina
authors.initials: A
authors.lastname: Agelidou
authors.forename: Aleka
authors.initials: A
authors.lastname: Gerogianni
authors.forename: Georgia
authors.initials: G
authors.lastname: Pavlakou
authors.forename: Evaggelos
authors.initials: E
authors.lastname: Tselepatiotis
authors.forename: John
authors.initials: J
authors.lastname: Nikolakopoulos
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin