title: Paclitaxel and carboplatin in combination with gemcitabine: a phase I-II trial in patients with advanced non-small-cell lung cancer. Gruppo Studio Tumori Polmonari Veneto (GSTPV).
abstract: BACKGROUND
  The combination of paclitaxel (P) and carboplatin (C) is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active new drug. We planned a phase I study to find the maximum tolerated dose (MTD) of the PCG combination. A phase II study was subsequently conducted to evaluate the activity and toxicity of PCG.
  
  
  METHODS
  Forty-five patients entered the study. Twenty-eight had stage IIIA-B disease, 17 stage IV. In the phase I study, with a fixed dose of C at AUC = 6 on day 1, P was escalated using increments of 25 mg/m2 starting from 175 mg/m2 on day 1 and G with increments of 200 mg/m2 starting from 800 mg/m2 on day 1 and 8.
  
  
  RESULTS
  Fourteen patients entered the phase I study. The MTD was reached at P 200 mg/m2, C AUC = 6 and G 1000 mg/m2. Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities. Thirty-one patients were treated in the phase II study with P 175 mg/m2, C AUC = 6 and G 1000 mg/m2. Response rate was 57% (68% in stage III and 47% in stage IV). Myelosuppression was the main toxicity, with grade 3-4 leukopenia occurring in 35% of cases. Grade 3 anemia was observed in 24% of cases and grade 3-4 thrombocytopenia occurred in 34% of patients. Non-hematological toxicity was mild. Median survival and one-year actuarial survival were 20.5 months and 74% for stage III and 11.5 months and 47% for stage IV.
  
  
  CONCLUSIONS
  PCG is a promising regimen for treating advanced NSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin in advanced NSCLC is ongoing. On the other hand, we are planning to introduce the PCG regimen in the treatment of stage II-III patients in the setting of a multimodality treatment.
authors.affiliation: Medical Oncology Department, Azienda Ospedaliera Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Favaretto
authors.forename: G L
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: A
authors.initials: A
authors.lastname: Paccagnella
authors.forename: F
authors.initials: F
authors.lastname: Barbieri
authors.forename: A
authors.initials: A
authors.lastname: Bearz
authors.forename: C
authors.initials: C
authors.lastname: Ghiotto
authors.forename: F
authors.initials: F
authors.lastname: Oniga
authors.forename: S
authors.initials: S
authors.lastname: Schiavon
authors.forename: S
authors.initials: S
authors.lastname: Frustaci
authors.forename: E
authors.initials: E
authors.lastname: Villa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D005260:Female; D005334:Fever / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D015993:Life Tables; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine