title: Phase-I study of sagopilone in combination with cisplatin in chemotherapy-naive patients with metastasised small-cell lung cancer.
abstract: BACKGROUND
  Sagopilone (ZK219477) is a new and fully synthetic epothilone with activity against multi-drug resistant tumour cell lines. It has demonstrated clinical activity in several solid tumours like ovarian cancer and melanoma. Data about clinical efficacy of sagopilone in small-cell lung cancer are lacking. Here we report the first phase-I trial of sagopilone in combination with cisplatin in previously untreated metastatic small-cell lung cancer patients.
  
  
  METHODS
  Chemonaive patients with metastatic small-cell lung cancer (SCLC) received sagopilone in four different dosing schedules ranging from 12 to 22 mg/m(2) (on day 1 as 3-h infusion) followed by a fixed dose of cisplatin of 75 mg/m(2) as 1-h infusion on day 1. Chemotherapy was administered every 3 weeks to a maximum of six cycles. The primary objective was determination of dose-limiting toxicities (DLTs) and the maximum-tolerated dose (MTD) in this setting. Secondary objectives were assessment of objective response rates (ORR) as well as investigation of sagopilone pharmacokinetics.
  
  
  RESULTS
  Twenty-six patients received a total of 107 treatment cycles of the platinum-sagopilone doublet. The recommended phase-II dose (RD) and schedule was found to be 19 mg/m(2) sagopilone followed by 75 mg/m(2) cisplatin. Peripheral neuropathy turned out as dose-limiting toxicity when the combination was administered over a median of four cycles. Objective responses were observed in six out of seven SCLC patients (85.7%) treated with the RD.
  
  
  CONCLUSIONS
  Sagopilone and cisplatin can be safely combined in the first-line treatment of metastasised SCLC. This combination demonstrated preliminary efficacy and should be further evaluated within phase-II trials.
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen of the University Duisburg-Essen, Essen, Germany. Electronic address: thomas.gauler@uk-essen.de.
authors.forename: Thomas Christoph
authors.initials: TC
authors.lastname: Gauler
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen of the University Duisburg-Essen, Essen, Germany; University of Colorado Denver, Department of Medicine, Division of Medical Oncology, Aurora, CO, USA.
authors.forename: Daniel Christian
authors.initials: DC
authors.lastname: Christoph
authors.affiliation: Department of Medical Oncology, Center for Thoracic Surgery and Pneumology, Clinic Loewenstein, Loewenstein, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Department of Medical Oncology, Dr. Horst-Schmidt Kliniken, Wiesbaden, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Frickhofen
authors.affiliation: Division of Pneumology, Department of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Huber
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Gonschorek
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Roth
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Giurescu
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen of the University Duisburg-Essen, Essen, Germany.
authors.forename: Wilfried Ernst Erich
authors.initials: WE
authors.lastname: Eberhardt
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D052160:Benzothiazoles / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D011446:Prospective Studies
chemical_list: D052160:Benzothiazoles; D034261:Epothilones; C530494:sagopilone; D002945:Cisplatin