Combination Chemotherapy With Gemcitabine Plus Oxaliplatin in Patients With Intensively Pretreated or Refractory Germ Cell Cancer: A Study of the German Testicular Cancer Study Group C. Kollmannsberger, J. Beyer, R. Liersch, P. Schoeffski, B. Metzner, O. Rick, J.T. Hartmann, K. Stengele, K. Hohloch, C. Spott, L. Kanz, and C. Bokemeyer A B S T R A C T Purpose Long-term survival is rarely achieved in patients with cisplatin-refractory germ cell cancer (GCT). Both single-agent gemcitabine and oxaliplatin have shown activity in patients who experience relapse or are refractory to cisplatin treatment. This study investigates the activity of a gemcitabine plus oxaliplatin regimen in these patients. Patients and Methods Gemcitabine was administered at a dose of 1,000 mg/m 2 on days 1 and 8; oxaliplatin was administered at a dose of 130 mg/m 2 on day 1. Response was evaluated every 4 weeks. Results Thirty-five patients with a median age of 37 years (range, 21 to 54 years) were enrolled onto the study. Primary tumor localization was gonadal, retroperitoneal, or mediastinal in 30, one, and four patients, respectively. Patients had been pretreated with a median of six platinum-containing cycles (range, four to 13 cycles) and 89% of patients previously had experienced treatment failure after high-dose chemotherapy with peripheral-blood stem-cell transplantation. Sixty-three percent of patients were considered absolutely cisplatin-refractory or cisplatin-refractory. A median of two cycles (range, 1 to 6 cycles) per patient were applied. Toxicity consisted mainly of myelosuppression, with Common Toxicity Criteria grade 3 occurring in 54% of patients. Only 9% of patients developed neutropenic fever. Three patients attained a complete remission (CR), two patients attained a marker-negative partial remission, and 11 patients attained a marker-positive partial remission, resulting in an overall response rate of 46% (95% CI, 30% to 64%). All three patients with CR and one patient with a marker-negative partial remission remained disease free at 16+, 12+,4+, and 2+ months of follow-up. Seven (44%) of these 16 responses, including one CR, occurred in cisplatin-refractory patients. Conclusion Gemcitabine plus oxaliplatin demonstrates antitumor activity with acceptable toxicity in heavily pre- treated patients with relapsed or cisplatin-refractory GCT, and may offer a chance of long-term survival for selected patients. J Clin Oncol 22:108-114. © 2004 by American Society of Clinical Oncology INTRODUCTION The treatment of patients with intensively pretreated or cisplatin-refractory metastatic germ cell cancer remains a therapeutic chal- lenge. Although 70% to 80% of patients with metastatic germ cell cancer will be cured with cisplatin-based combination chemo- therapy, patients who experience disease progression during cisplatin-based chemo- therapy or experience relapse after salvage treatment achieve long-term survival rates of less than 5% [1-3]. Therefore, the evalua- tion of new drugs with significant antitumor activity remains a priority in these heavily pretreated patients. Only four agents have thus far demonstrated single-agent activity in these patients; continuously applied low- dose oral etoposide, paclitaxel, gemcitabine, and, most recently, oxaliplatin, are active in From the Department of Hematology/ Oncology, University of Tuebingen Medical Center, Tuebingen; Depart- ment of Hematology/Oncology, Univer- sity of Marburg, Marburg; Department of Hematology/Oncology, University of Muenster, Muenster; Department of Hematology/Oncology, University of Hannover Medical School, Hannover; Department of Hematology/Oncology, Klinikum Oldenburg, Oldenburg; Depart- ment of Hematology/Oncology, Charite, University of Berlin, Berlin; Department of Hematology/Oncology, Hegau-Klini- kum, Singen; and Department of Hema- tology/Oncology, University of Goettin- gen, Goettingen, Germany. Submitted June 17, 2003; accepted October 27, 2003. Supported by an educational grant from Sanofi-Synthelabo Inc, Berlin, Germany. These data were presented in part at the 39th Annual Meeting of the Ameri- can Society of Clinical Oncology Meet- ing, Chicago, IL, May 31-June 3, 2003. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to C. Bokemeyer, MD, Department of Hematology/Oncology, University of Tuebingen Medical Center, Otfried- Mueller-Str 10, 72076 Tuebingen, Germany; e-mail: carsten.bokemeyer@ med.uni-tuebingen.de. © 2004 by American Society of Clinical Oncology 0732-183X/04/2201-108/$20.00 DOI: 10.1200/JCO.2004.06.068 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 22  NUMBER 1  JANUARY 1 2004 108 Downloaded from ascopubs.org by 3.80.23.4 on May 31, 2022 from 003.080.023.004 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.