Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer

J Clin Oncol. 2001 Jan 1;19(1):81-8. doi: 10.1200/JCO.2001.19.1.81.

Abstract

Purpose: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors.

Patients and methods: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2), ifosfamide 5 x 1.2 g/m(2), and cisplatin 5 x 20 mg/m(2) (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m(2) x 3, etoposide 600 mg/m(2) x 4, and thiotepa 150 to 250 mg/m(2) x 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (TI) was given immediately before TIP to improve stem-cell mobilization.

Results: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects.

Conclusion: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Disease-Free Survival
  • Germany / epidemiology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Ifosfamide / administration & dosage
  • Male
  • Mediastinal Neoplasms / therapy
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Neoplasms, Germ Cell and Embryonal / therapy*
  • Paclitaxel / administration & dosage
  • Salvage Therapy / methods*
  • Survival Rate
  • Testicular Neoplasms / therapy
  • Thiotepa / administration & dosage

Substances

  • Thiotepa
  • Paclitaxel
  • Cisplatin
  • Ifosfamide