title: Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group.
abstract: OBJECTIVE
  In a previous phase I study cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR) combination therapy was safe and very active in patients with non-small-cell lung cancer (NSCLC). This study was aimed at better defining the activity and toxicity of this regimen.
  
  
  METHODS
  One hundred eleven chemotherapy-naive patients, age < or = 70 years, with stage IIIB or IV NSCLC and a performance status of 0 or 1 (Eastern Cooperative Oncology Group scale) were randomized to two treatment arms. Patients on arm A received CDDP 50 mg/m2, GEM 1,000 mg/m2, and VNR 25 mg/m2 on days 1 and 8 of an every-3-weeks cycle (57 patients). Patients on arm B received CDDP 80 mg/m2, epirubicin 80 mg/m2, and vindesine 3 mg/m2, all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients). In December 1996, randomization was stopped early, and an additional 30 patients were treated with the experimental regimen to obtain a more accurate estimation of its activity rate.
  
  
  RESULTS
  Among 87 patients who received the CDDP-GEM-VNR combination, four complete responses (CRs) and 46 partial responses (PRs) were observed, for an overall response rate of 57% (95% confidence interval [CI], 46% to 68%). Two CRs and 18 PRs were recorded among 54 patients on arm B, giving a 37% activity rate (95% CI , 24% to 51%). After a median follow-up duration of 19 months, the median progression-free and overall survival durations were 32 and 50 weeks in arm A, and 18 and 33 weeks in arm B, respectively. World Health Organization grade 3 to 4 neutropenia and thrombocytopenia occurred in 46% and 14% of patients in arm A and in 22% and 11% of those in arm B, respectively. Severe nonhematologic toxicity was uncommon in both arms.
  
  
  CONCLUSIONS
  The CDDP-GEM-VNR combination is a highly effective treatment for patients with advanced NSCLC and has a manageable toxicity. A phase III trial comparing this new combination with both CDDP-VNR and CDDP-GEM regimens is underway.
authors.affiliation: Division of Medical Oncology A, National Tumor Institute, Naples, Italy. pcomella@sirio-oncology.it
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: G
authors.initials: G
authors.lastname: Frasci
authors.forename: N
authors.initials: N
authors.lastname: Panza
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: G
authors.initials: G
authors.lastname: Di Rienzo
authors.forename: R
authors.initials: R
authors.lastname: Cioffi
authors.forename: G
authors.initials: G
authors.lastname: De Cataldis
authors.forename: L
authors.initials: L
authors.lastname: Maiorino
authors.forename: D
authors.initials: D
authors.lastname: Bilancia
authors.forename: G
authors.initials: G
authors.lastname: Nicolella
authors.forename: M
authors.initials: M
authors.lastname: Natale
authors.forename: F
authors.initials: F
authors.lastname: Carpagnano
authors.forename: C
authors.initials: C
authors.lastname: Pacilio
authors.forename: M
authors.initials: M
authors.lastname: De Lena
authors.forename: A
authors.initials: A
authors.lastname: Bianco
authors.forename: G
authors.initials: G
authors.lastname: Comella
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011788:Quality of Life; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014751:Vindesine / Q000008:administration & dosage / Q000009:adverse effects; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D007191:Indazoles; D003841:Deoxycytidine; D015251:Epirubicin; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D014751:Vindesine; C016371:lonidamine; D000093542:Gemcitabine