title: Cisplatin, gemcitabine, and paclitaxel in locally advanced or metastatic non-small-cell lung cancer: a phase I-II study. Southern Italy Cooperative Oncology Group.
abstract: OBJECTIVE
  Because both cisplatin-paclitaxel and cisplatin-gemcitabine combinations are generally considered to be among the most active regimens in non-small-cell lung cancer (NSCLC) patients, this study aimed to determine the maximum-tolerated dose (MTD) of paclitaxel when combined with fixed doses of cisplatin and gemcitabine in advanced NSCLC patients and aimed to define the therapeutic activity of this new regimen.
  
  
  METHODS
  From October 1996 to September 1998, 75 patients with stage IIIB-IV NSCLC, who were either chemotherapy-naive (65 patients) or who had been pretreated (10 patients), received fixed doses of cisplatin (50 mg/m(2)) and gemcitabine (1,000 mg/m(2)) and escalating doses of paclitaxel in a 1-hour infusion, all on days 1 and 8, every 3 weeks.
  
  
  RESULTS
  Five different paclitaxel doses were tested, for a total of 275 cycles delivered. The escalation was stopped at the paclitaxel dose of 75 mg/m(2) in pretreated patients, whereas it continued to 150 mg/m(2) in chemotherapy-naive patients. A total of 65 chemotherapy-naive patients were treated. A paclitaxel dose of 125 mg/m(2) was recommended for phase II, and a total of 39 patients were treated at this level, for a total of 158 cycles delivered. No treatment-related deaths occurred. Five patients were hospitalized because of sepsis, and packed RBC transfusion was required in 13 patients. Grade 4 neutropenia and thrombocytopenia occurred in 23 (31%) and eight (11%) patients, respectively. Overall, 74 of the 75 patients were assessable for response. Four complete (CR) and 38 partial (PR) responses were recorded, for an overall response rate (ORR) of 57%. Three of the ten pretreated patients achieved a PR, compared with four CRs and 35 PRs in the 64 chemotherapy-naive patients (ORR, 61%). Thirty-eight of 39 patients included in phase II were assessable for response and quality of life (QOL) (one patient's disease was not measurable). Two CRs and 24 PRs were recorded in this group, for an ORR of 68% (95% confidence interval, 51% to 82%). The QOL score improved in 27 of 38 (71%) patients. The median survival time was 15 months in the 65 chemotherapy-naive patients, but it had not yet been reached in the 39 patients included in phase II, for whom the 1-year projected survival was 70%.
  
  
  CONCLUSIONS
  The cisplatin-gemcitabine-paclitaxel combination is a feasible and well-tolerated approach in advanced NSCLC patients. Both a major response and a QOL improvement can be obtained in a high proportion of patients, with a median survival time exceeding 1 year. A phase III trial comparing this combination with other effective regimens is under way.
authors.affiliation: Southern Italy Cooperative Oncology Group, National Tumor Institute of Naples, Naples, Italy. gifrasei@sirio-oncology.it
authors.forename: G
authors.initials: G
authors.lastname: Frasci
authors.forename: N
authors.initials: N
authors.lastname: Panza
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: G P
authors.initials: GP
authors.lastname: Nicolella
authors.forename: M
authors.initials: M
authors.lastname: Natale
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: D
authors.initials: D
authors.lastname: Bilancia
authors.forename: R
authors.initials: R
authors.lastname: Cioffi
authors.forename: L
authors.initials: L
authors.lastname: Maiorino
authors.forename: G
authors.initials: G
authors.lastname: De Cataldis
authors.forename: M
authors.initials: M
authors.lastname: Belli
authors.forename: E
authors.initials: E
authors.lastname: Micillo
authors.forename: V
authors.initials: V
authors.lastname: Mascia
authors.forename: B
authors.initials: B
authors.lastname: Massidda
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: M
authors.initials: M
authors.lastname: De Lena
authors.forename: F
authors.initials: F
authors.lastname: Carpagnano
authors.forename: A
authors.initials: A
authors.lastname: Contu
authors.forename: G
authors.initials: G
authors.lastname: Pusceddu
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* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine