title: Cisplatin versus carboplatin in combination with mitomycin and vinblastine in advanced non small cell lung cancer. A multicenter, randomized phase III trial.
abstract: BACKGROUND
  In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1-2 months on median survival versus best supportive care. Chemotherapy seems to improve symptoms control, even if randomised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio. The aim of the present study is to evaluate the impact on QoL, substituting cisplatin, a pivot drug in NSCLC therapy, with carboplatin, an analogue with an improved toxicity profile. The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study.
  
  
  METHODS
  Patients were randomized to receive MVP regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Cisplatin 100 mg/m2 d1) or MVC regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Carboplatin 300 mg/m2 d1) every 3 weeks. The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 questionnaires before chemotherapy, after one cycle, after three cycles, and then every 6 weeks in the first 6 months and every 3 months thenafter.
  
  
  RESULTS
  From September 1994 to July 1997, 153 consecutive patients were randomized to MVP (75 patients) or MVC arm (78 patients). Despite difficulties in carrying out and analysing QoL items in such patients, the global QoL evaluated by the Spitzer's questionnaire suggested an advantage for MVC regimen (P=0.05) and a significant difference was observed in global health subdomain (P=0.04). The disease-related symptoms improved with time, and the benefits lasted for the entire treatment period. When evaluated with the EORTC questionnaire there was significantly less nausea and vomiting (P=0.0001), appetite loss (P=0.01), insomnia (P=0.03), constipation (P=0.01) and peripheral neuropathy (P=0.01) in favour of MVC, and a trend for less hair loss (P=0.05). The advantage lasted for all the duration of chemotherapy. No differences were observed in global quality of life subdomain (P=0.40) between the two regimen. QoL was the first endpoint and the statistical power was inadequate to assess other parameters. However, we reported a response rate of 43.1 and 38.6%, respectively, in MVP and MVC arm (P=0.59) and a median survival of 10.2 and 7.2 months, respectively, for cisplatin and carboplatin arm (P=0.39).
  
  
  CONCLUSIONS
  The carboplatin containing regimen (MVC) has a significant better toxicity profile than the cisplatin containing (MVP) regimen as proven both by the EORTC questionnaires and by the WHO toxicity data reported by physicians. No significant differences in terms of response rate, time to progression and overall survival were observed between the two regimen. The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL questionnaire. With the Spitzer's questionnaires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination. This difference, however, was not observed when the global quality of life was evaluated with the EORTC patients compiled questionnaires. A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC.
authors.affiliation: Department of Medical Oncology, SS Giovanni and Paolo Hospital, Campo S Giovanni e Paolo, 30100 Venice, Italy. Adriano@ulss12.ve.it
authors.forename: Adriano
authors.initials: A
authors.lastname: Paccagnella
authors.forename: A
authors.initials: A
authors.lastname: Favaretto
authors.forename: F
authors.initials: F
authors.lastname: Oniga
authors.forename: F
authors.initials: F
authors.lastname: Barbieri
authors.forename: G
authors.initials: G
authors.lastname: Ceresoli
authors.forename: W
authors.initials: W
authors.lastname: Torri
authors.forename: E
authors.initials: E
authors.lastname: Villa
authors.forename: C
authors.initials: C
authors.lastname: Verusio
authors.forename: G L
authors.initials: GL
authors.lastname: Cetto
authors.forename: A
authors.initials: A
authors.lastname: Santo
authors.forename: V
authors.initials: V
authors.lastname: De Pangher
authors.forename: F
authors.initials: F
authors.lastname: Artioli
authors.forename: G C
authors.initials: GC
authors.lastname: Cacciani
authors.forename: G
authors.initials: G
authors.lastname: Parodi
authors.forename: F
authors.initials: F
authors.lastname: Soresi
authors.forename: M G
authors.initials: MG
authors.lastname: Ghi
authors.forename: A
authors.initials: A
authors.lastname: Morabito
authors.forename: R
authors.initials: R
authors.lastname: Biason
authors.forename: M
authors.initials: M
authors.lastname: Giusto
authors.forename: P
authors.initials: P
authors.lastname: Mosconi
authors.forename: V
authors.initials: V
authors.lastname: Chiarion Sileni
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D016685:Mitomycin; D014747:Vinblastine; D016190:Carboplatin; D002945:Cisplatin