High-dose ifosfamide as second- or third-line chemotherapy in refractory bone and soft tissue sarcoma patients

Oncology. 2011;80(3-4):257-61. doi: 10.1159/000328795. Epub 2011 Jul 6.

Abstract

Introduction: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS.

Patients and methods: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1-8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m(2) over 3 h, and at a dose of 2 g/m(2) per day; continuous infusion was administered on 6 consecutive days (2 g/m(2)/6 days) every 3 weeks.

Results: After a median follow-up of 49 months (range 10-114), median PFS was 2.9 months (range 0.4-9.3) and median overall survival 8.7 months (range 0.4-57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7-7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3-4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient.

Conclusion: HDI at a total dose of 14 g/m(2) with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neutropenia / etiology
  • Retrospective Studies
  • Salvage Therapy*
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / pathology
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Ifosfamide