title: Evaluation of irinotecan plus paclitaxel in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel in patients with advanced stage non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients were eligible if they had histologically confirmed chemotherapy naïve stage IV NSCLC or stage IIIB disease that was not suitable for combined modality therapy. Patients were treated with irinotecan 50 mg/m2 and paclitaxel 75 mg/m2 on days 1 and 8 of a 21-day cycle. If the patient did not experience >grade 1 toxicity during the first cycle, the dose of irinotecan could be escalated to 60 mg/m(2). Patients were evaluated for tumor response rate, time to progression (TTP), overall survival (OS) and toxicity.
  
  
  RESULTS
  Twenty-three eligible patients were treated. Two (9%) patients achieved a partial response. Eight patients (35%) had stable disease. The median number of cycles given per patient was four (range 1-29). The major toxicities were grade >or=3 neutropenia (26%) and grade 3 diarrhea (5%). The median time to progression was 2.8 months (range 0.5-21.8 months) for all patients and 4.3 months for the patients who had either stable disease or a partial response. The median overall survival was 9.2 months (range 0.5-40 months). The one- and two-year survival rates were 39% and 13%, respectively.
  
  
  CONCLUSIONS
  The combination of irinotecan and paclitaxel is safe in advanced NSCLC and affords a survival similar to other non-platinum as well as platinum-based doublets. However, this combination does not have sufficient activity to justify further study in an unselected population. If biomarkers are developed that can guide the selection of chemotherapy in an individual patient, there may be a rationale for further evaluation of this regimen.
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut 06520-8032, USA. john.murren@yale.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Murren
authors.forename: Nicolaj
authors.initials: N
authors.lastname: Andersen
authors.forename: Diamando
authors.initials: D
authors.lastname: Psyrri
authors.forename: Deborah
authors.initials: D
authors.lastname: Brandt
authors.forename: Rajani
authors.initials: R
authors.lastname: Nadkarni
authors.forename: Michal
authors.initials: M
authors.lastname: Rose
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Nicole
authors.initials: N
authors.lastname: Parisot
authors.forename: Arthur T
authors.initials: AT
authors.lastname: Rosenfield
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Pizzorno
authors.forename: Daniel
authors.initials: D
authors.lastname: Zelterman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin