Combination of paclitaxel, cisplatin, and gemcitabine (TPG) for multiple relapses or platinum-resistant germ cell tumors: long-term outcomes

Clin Genitourin Cancer. 2014 Feb;12(1):63-69.e1. doi: 10.1016/j.clgc.2013.07.005. Epub 2013 Oct 23.

Abstract

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.

Keywords: Chemotherapy; Germ cell tumors; Salvage therapy; Testicular cancer.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use*
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / surgery
  • Paclitaxel / adverse effects
  • Paclitaxel / therapeutic use*
  • Retrospective Studies
  • Salvage Therapy
  • Survival
  • Treatment Outcome

Substances

  • Deoxycytidine
  • Paclitaxel
  • Cisplatin
  • Gemcitabine