Combination of Paclitaxel, Cisplatin, and Gemcitabine (TPG) for Multiple Relapses or Platinum-Resistant Germ Cell Tumors: Long-Term Outcomes

A low but invariable proportion of patients with advanced germ cell tumors still fail to be cured by first-line chemotherapy, and the number of life years lost is one of the highest among solid tumors. For patients with chemoresistant disease, the readministration of cisplatin, combined with paclitaxel and gemcitabine (TPG), was tolerable and provided long-term remissions in otherwise incurable patients. Background: Rescue of patients who fail to be cured after 2 or 3 chemotherapy combinations (including high-dose chemotherapy [HDCT]) or whose disease is refractory to cisplatin is still an unmet need. We assessed the efficacy of a triple-combination chemotherapy in the salvage setting, beyond second-line regimens. Patients and Methods: We retrospectively reviewed institutional data on consecutive patients who received paclitaxel 80 mg/m(2) intravenously (IV), cisplatin 50 mg/m(2) IV, and gemcitabine 800 mg/m(2) IV on days 1 and 8 every 3 weeks for a maximum of 8 administrations, followed by surgery. Response, survival (progression-free survival [PFS] and overall survival [OS]), and safety/toxicity outcomes were the end points. The Kaplan-Meier method was used for survival estimates, and multiple Cox regression models were used to analyze the prognostic factors. Results: Seventy-five patients were treated from April 1999 to July 2011. Eight complete responses (CR, 10.7%), 29 partial responses with normal markers (PRm(-), 38.7%), and 13 cases of incomplete response/stable disease were recorded, for a major response rate (CR + PRm(-)) of 49%. Thirty-three patients (44%) underwent surgery, which was radical in 14 cases (42.4%). Two-year PFS was 14.8% (95% confidence interval [CI], 8.5%-25.8%), whereas 2-year OS was 29.5% (95% CI, 20.3%-42.7%). Five-year OS in disease-free patients (no evidence of disease) was 60.3% (95% CI, 42.2%-86.2%), and median OS between patients with and without evidence of disease was significantly different (71 [interquartile range {IQR}, 14-116] vs. 12.5 [IQR, 8-19] months with a 6-month landmark analysis; P=.0019). Conclusion: TPG is an effective combination, and best results were achieved if a radical clearance of residual disease could be accomplished. A randomized comparison with dose-intensified regimens is advisable. (C) 2014 Elsevier Inc. All rights reserved.