title: Phase I study of docetaxel and irinotecan in patients with advanced non-small-cell lung cancer.
abstract: The role of non-platinum combination chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has not yet been clarified. In this phase I study, the dose-limiting toxicity (DLT), the maximum tolerable dose (MTD) and the antitumor activity of a two-drug combination of docetaxel (DCT) and irinotecan (CPT) in patients with advanced NSCLC were evaluated. Previously untreated patients with NSCLC in stage IIIB with malignant pleural effusion or stage IV were eligible. Both drugs were administered by 1-h intravenous infusion on day 1, and repeated every 3 weeks. DCT was given before CPT administration. Five escalating dose levels of DCT/CPT (40/135, 50/135, 50/150, 60/150, and 60/165 mg/m2) were studied. Eighteen patients received 44 courses. The DLT was considered to be neutropenia, because grade 4 neutropenia lasting for 3 days or more was observed in three patients, which was accompanied with three episodes of febrile neutropenia. As a non-hematological toxicity, grade 3 diarrhea occurred in three patients. Since all the three patients treated at the fifth dose level (DCT at 60 mg/m2 and CPT at 165 mg/m2) experienced DLT (grade 4 neutropenia in two patients and grade 3 hepatic toxicity in one), this dose level was determined to be the MTD. The objective response rate was 33.3%, and the median survival time was 13.6 months. To confirm the effectiveness of this combination for advanced NSCLC which was suggested in the present study, a phase II study with the recommended doses (150 mg/m2 for CPT and 50-60 mg/m2 for DCT) is warranted.
authors.affiliation: Department of Internal Medicine II, Okayama University Medical School, 2-5-1 Shikatacho, Okayama, Okayama Prefecture 700-8558, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.forename: Shingo
authors.initials: S
authors.lastname: Harita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yonei
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Haruhito
authors.initials: H
authors.lastname: Kamei
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Gemba
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D002166:Camptothecin