title: Weekly irinotecan combined with carboplatin for patients with small-cell lung cancer: A phase I study.
abstract: BACKGROUND
  We conducted a phase I dose escalation study to evaluate the feasibility, maximum tolerated dose (MTD), and recommended dose (RD) of weekly irinotecan combined with fixed-dose carboplatin for patients with untreated small-cell lung cancer (SCLC).
  
  
  METHODS
  Fifteen patients with chemotherapy-naïve SCLC less than 75 years old were enrolled from 3 institutions. Patients received irinotecan (50-80mg/m(2) on days 1 and 8) and carboplatin (area under the curve, 5.0 on day 1) every 3 weeks, with 3-6 patients treated at each irinotecan dosage level (levels I-IV). The MTD was defined as the dose at which 33% of patients experienced dose-limiting toxicity.
  
  
  RESULTS
  Eleven patients had a performance status of 1, and 7 patients were more than 70 years old. All but 1 patient were diagnosed with extensive disease. In total, 2 of 3 patients enrolled at level IV (80mg/m(2)) experienced grade 3 diarrhea. Therefore, the MTD was defined as the level IV dose, and the RD was defined as the level III dose (70mg/m(2)). Grade 3 or 4 neutropenia was observed in 60% of patients, and febrile neutropenia was observed in 13% of patients. Four patients experienced grade 3 or 4 anemia, and 6 patients experienced grade 3 or 4 thrombocytopenia. The most common non-hematological adverse events were nausea/vomiting, diarrhea, hypokalemia, and hyponatremia.
  
  
  CONCLUSIONS
  The MTD of weekly irinotecan was 80mg/m(2), resulting in an RD of 70mg/m(2) for phase II trials.
authors.affiliation: Sendai Kousei Hospital, 4-15 Hirosemachi, Aobaku, Sendai, Miyagi 980-0873, Japan. Electronic address: ishimto@crest.ocn.ne.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishimoto
authors.affiliation: Sendai Kousei Hospital, 4-15 Hirosemachi, Aobaku, Sendai, Miyagi 980-0873, Japan. Electronic address: swara357@cat-v.ne.jp.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-0872, Japan. Electronic address: akinoue@idac.tohoku.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Miyagi Cancer Center, 47-1 Shiodeaza Medeshima, Natori, Miyagi 981-1239, Japan. Electronic address: maemondo-ma693@aioros.ocn.ne.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.affiliation: Japan Anti-Tuberculosis Association, 1-3-12 Misakicho, Chiyoda-ku, Tokyo 101-0061, Japan. Electronic address: tnukiwa@jatahq.org.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D005240:Feasibility Studies; D064147:Febrile Neutropenia / Q000139:chemically induced; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced; D007010:Hyponatremia / Q000139:chemically induced; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin
keywords: Carboplatin; Chemotherapy; Irinotecan; Phase I study; Small-cell lung cancer