title: A combination chemotherapy of carboplatin and irinotecan with granulocyte colony-stimulating factor (G-CSF) support in elderly patients with small cell lung cancer.
abstract: BACKGROUND
  We have previously reported that carboplatin plus etoposide is an effective and relatively non-toxic regimen in elderly patients with small cell lung cancer (SCLC). Recently, the Japan Clinical Oncology Group reported that irinotecan plus cisplatin was more effective than etoposide plus cisplatin in the treatment of non-elderly patients with extensive disease (ED)-SCLC. Therefore, we conducted a prospective feasibility study designed specifically to evaluate the efficacy of carboplatin (day 1) and irinotecan (days 1, 8, 15) with granulocyte colony-stimulating factor (G-CSF) support in elderly SCLC patients.
  
  
  METHODS
  Three carboplatin AUC and irinotecan dose levels were used: 4 mg/ml x min and 50 mg/m2, respectively (level 1); 5 mg/ml x min and 50 mg/m2, respectively (level 2), and 5 mg/ml x min and 60 mg/m2, respectively (level 3). Although a phase I trial using this drug combination against non-SCLC performed at our institution found that the recommended dose was level 3, as the current trial included only elderly patients, the starting dose used was level 2. However, if a patient had history of prior chemotherapy, performance status (PS) of 2, or was aged 75 years or more, the dose administered was reduced by 1 level. If a patient had a PS of 0, the dose was increased by 1 level. Cycles were repeated every 4 weeks, and patients aged 70 years or more with a PS of 0-2 were eligible.
  
  
  RESULTS
  Eighteen patients were enrolled, of which nine were given the level 1 dose, seven the level 2 dose, and two the level 3 dose. The patient group had a median age of 75 years, 8 patients had limited disease (LD) versus 10 with ED, 9 had received previous treatment for SCLC versus 9 previously untreated, and 13 had a PS of 0-1 versus 5 with a PS of 2. Seventeen (94%) patients received two or more cycles of chemotherapy, and the median actual delivery of irinotecan was 84% of the projected dose. Grade 3/4 neutropenia, anemia, and diarrhea occurred in 50%, 33% and 6% of patients, respectively. Other toxicities were mild and no treatment-related deaths occurred. The response rate was 89%, with two complete responses and 14 partial responses. The median survival time was 13.3 months and the 1-year survival rate was 62%.
  
  
  CONCLUSIONS
  The combination of carboplatin and irinotecan with G-CSF support was an effective and non-toxic regimen in elderly SCLC patients and should be further evaluated in phase III trials.
authors.affiliation: Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan. scyooka@alles.or.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naoki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Narita
authors.forename: Naoya
authors.initials: N
authors.lastname: Hida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunikane
authors.forename: Koshiro
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin