title: Combination second-line chemotherapy with gemcitabine and docetaxel for recurrent non-small-cell lung cancer after platinum-containing chemotherapy: a phase I/II trial.
abstract: OBJECTIVE
  In a randomized trial, docetaxel monotherapy yielded longer survival than the best supportive care in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy, and combination chemotherapy regimens containing docetaxel have been assessed to enhance the efficacy of second-line chemotherapy. We conducted a phase I/II trial of gemcitabine and docetaxel in patients with recurrent NSCLC after platinum-based chemotherapy and with an ECOG performance status (PS) of 0 or 1.
  
  
  METHODS
  Docetaxel administration was fixed at a dosage of 60 mg/m(2) on day 8, and gemcitabine was administered on days 1 and 8. The starting dose level of gemcitabine was 800 mg/m(2) (level 0), and the subsequent dose level of gemcitabine was 1000 mg/m(2) (level +1). Treatment was repeated every 3 weeks.
  
  
  RESULTS
  In the phase I study, 13 patients were enrolled, and in the phase II study, 29 patients were enrolled. Neutropenic fever and omission of treatment on day 8 due to leukopenia (leukocyte count less than 3000/mm(3)) were dose-limiting toxicities (DLTs). Three of six patients experienced DLTs at level +1, which was the maximum tolerated dose. Gemcitabine 800 mg/m(2) on days 1 and 8 plus docetaxel 60 mg/m(2) on day 8 (level 0) was recommended for the phase II study. An objective response was observed in 8 (28%) of the 29 patients. The median time to disease progression was 4.2 months (95% CI 0.9-7.7 months). The median survival time was 11.1 months (95% CI 9.9-12.4 months), and the 1-year survival rate was 41%. The most common toxicity, though mild, was hematologic, and consisted of grade 4 neutropenia (18%), grade 3 febrile neutropenia (11%), and grade 3 thrombocytopenia (11%). There were no toxic deaths. Grade 3 non-hematologic toxicities included nausea (4%) and rash (4%).
  
  
  CONCLUSIONS
  The combination chemotherapy of gemcitabine and docetaxel is active and well tolerated in patients with recurrent NSCLC after platinum-based chemotherapy and with a good PS.
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha 6-5-1, Kashiwa, 277-8577 Chiba, Japan. siniho@east.ncc.go.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubota
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ohmatsu
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kakinuma
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishiwaki
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D043823:Taxoids; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine