Thomas Christoph Gauler1, Daniel Christian Christoph2, Juergen Fischer3, Norbert Frickhofen4, Rudolf Huber5, Christine Gonschorek6, Katrin Roth6, Marius Giurescu6, Wilfried Ernst Erich Eberhardt7. 1. 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. 2. 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. 3. Department of Medical Oncology, Center for Thoracic Surgery and Pneumology, Clinic Loewenstein, Loewenstein, Germany. 4. Department of Medical Oncology, Dr. Horst-Schmidt Kliniken, Wiesbaden, Germany. 5. Division of Pneumology, Department of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany. 6. Bayer Pharma AG, Berlin, Germany. 7. Department of Medical Oncology, West German Cancer Center, University Hospital Essen of the University Duisburg-Essen, Essen, Germany.
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.
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 cancerpatients. 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 SCLCpatients (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.