title: Two schedules of teniposide with or without cisplatin in advanced non-small-cell lung cancer: a randomized study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.
abstract: OBJECTIVE
  We conducted a randomized trial to investigate the value of the addition of cisplatin to teniposide (VM26) and to investigate the schedule dependence of the topoisomerase II inhibitor VM26, in advanced non-small-cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Two hundred twenty-five NSCLC patients were randomized to receive VM26 120 mg/m2 on days 1, 3, and 5 or 360 mg/m2 on day 1 only, either as a single drug or in combination with cisplatin 80 mg/m2 on day 1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study.
  
  
  RESULTS
  The response rate of the two cisplatin-containing arms was superior to that of the two arms that contained VM26 only (22% v 6%, P < .001); progression-free survival and survival times were also longer in the cisplatin-containing arms (median, 4.3 v 2.2 months, P = .003; median 7.2 v 5.9 months, P = .008, respectively). Toxicity was significantly higher in the cisplatin-containing arms; the most frequent side effects were leukopenia, nausea and vomiting, and alopecia. The schedule of VM26 did not significantly influence the response rate, progression-free survival interval, or survival duration. However, the response rate of the 1-day administration was significantly lower than that of the 3-day administration when given as single drugs.
  
  
  CONCLUSIONS
  The addition of cisplatin to VM26 improves the response rate, progression-free survival interval, and survival duration over VM26 alone, although at the cost of a significant increase in toxicity. Cisplatin should be considered as the basis for combination chemotherapies in advanced NSCLC.
authors.affiliation: University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: T A
authors.initials: TA
authors.lastname: Splinter
authors.forename: T
authors.initials: T
authors.lastname: Sahmoud
authors.forename: J
authors.initials: J
authors.lastname: Festen
authors.forename: N
authors.initials: N
authors.lastname: van Zandwijk
authors.forename: S
authors.initials: S
authors.lastname: Sörenson
authors.forename: M
authors.initials: M
authors.lastname: Clerico
authors.forename: J
authors.initials: J
authors.lastname: Burghouts
authors.forename: B
authors.initials: B
authors.lastname: Dautzenberg
authors.forename: G S
authors.initials: GS
authors.lastname: Kho
authors.forename: A
authors.initials: A
authors.lastname: Kirkpatrick
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D005163:Factor Analysis, Statistical; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016016:Proportional Hazards Models; D015996:Survival Rate; D013713:Teniposide / Q000008:administration & dosage*; D059005:Topoisomerase II Inhibitors
chemical_list: D059005:Topoisomerase II Inhibitors; D013713:Teniposide; D002945:Cisplatin