title: Phase I study of carboplatin, irinotecan and docetaxel on a divided schedule with recombinant human granulocyte colony stimulating factor support in patients with stage IIIB or IV non-small cell lung cancer.
abstract: A phase I study was conducted to determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of carboplatin combined with irinotecan and docetaxel on a divided schedule with recombinant human granulocyte colony stimulating factor (rhG-CSF) support in patients with stage IIIB or IV non-small cell lung cancer. Carboplatin was given at the dose of AUC5 on day 1. Irinotecan and docetaxel on days 1 and 8 were administered at a starting dose of 40 and 30 mg/m2 as level 1. Subsequent levels were: irinotecan/docetaxel (in mg/m2), 50/30 (level 2), 60/30 (level 3) and 60/35 (level 4). rhG-CSF was given at 50 mg/m2 on days 5-15. Cycles were repeated every 3 weeks. Between May 1999 and April 2001, 31 patients were registered in this phase I study. Level 4 was judged as the MTD. The DLTs were considered diarrhea and febrile neutropenia. The overall response rate was 32.3% and median survival was 490 days with 1-year survival of 65.1%. We conclude that both irinotecan 60 mg/m2 and docetaxel 30 mg/m2 on days 1 and 8 in combination with an AUC5 of carboplatin on day 1 with rhG-CSF support is recommended for phase II study. The response rate and survival data in this phase I study are encouraging. We considered that the pathogenesis of diarrhea involved not only direct cytotoxic damage to the mucosa, but also bacterial overgrowth.
authors.affiliation: Division of Respiratory Disease, Minami-ichijo Hospital, Sapporo 060-0061, Japan. afujita@sa2.so-net.ne.jp
authors.forename: Akihisa
authors.initials: A
authors.lastname: Fujita
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hoshino
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Takabatake
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tagaki
authors.forename: Kyuhichiro
authors.initials: K
authors.lastname: Sekine
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011994:Recombinant Proteins / Q000008:administration & dosage; D043823:Taxoids
chemical_list: D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D000077146:Irinotecan; D016190:Carboplatin; D017239:Paclitaxel; D002166:Camptothecin