Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial

Pediatr Blood Cancer. 2008 Apr;50(4):739-45. doi: 10.1002/pbc.21494.

Abstract

Purpose: We prospectively studied the efficacy of high dose therapy (HDT) versus an oral maintenance treatment (OMT) in patients with stage IV soft tissue sarcoma (STS).

Patients and methods: Both groups were pretreated with the CEVAIE combination consisting of carboplatin, etoposide, vincristine, actinomycin D, ifosfamide, and epirubicin. HDT consisted of a tandem cycle of thiotepa (600 mg/m(2)) plus cyclophosphamide (4,500 mg/m(2)) and melphalan (120 mg/m(2)) plus etoposide (1,800 mg/m(2)). This treatment was compared with OMT, consisting of four cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus etoposide (10 days 2 x 25 mg/m(2)/day), and 4 cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus idarubicin (10 days 4 x 5 mg/m(2)). Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy.

Results: From 96 patients 45 were treated with HDT and 51 with OMT. The main risk parameters were equally distributed in both arms. After a median follow-up of 57.4 months, 11/45 (24.4%) patients in the HDT-arm and 26/51 (57.8%) patients in OMT-arm were alive. Kaplan-Meier analysis demonstrated an overall survival for the whole group of 0.27 (OMT group: 0.52, HDT group 0.27, log rank P = 0.03). The proportional hazard analysis for patients with rhabdomyosarcoma (RMS) or "RMS-like" tumors (77.1% of all patients) demonstrated an independent benefit of OMT on outcome.

Conclusion: Oral maintenance therapy seems to be a promising option for patients with RMS-like stage IV tumors.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / analogs & derivatives
  • Dactinomycin / administration & dosage
  • Epirubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Idarubicin / administration & dosage
  • Ifosfamide / administration & dosage
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / administration & dosage
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality
  • Thiotepa / administration & dosage
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Dactinomycin
  • Epirubicin
  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Thiotepa
  • Carboplatin
  • trofosfamide
  • Melphalan
  • Ifosfamide
  • Idarubicin