Hyperthermic isolated perfusion with low-dose tumor necrosis factor alpha and doxorubicin for the treatment of limb-threatening soft tissue sarcomas.

Carlo Riccardo Rossi, Simone Mocellin, Pierluigi Pilati, Mirto Foletto, Luca Campana, Luigi Quintieri, Gian Luca De Salvo, Mario Lise

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Tumor necrosis factor (TNF)-alpha-based hyperthermic isolated limb perfusion (HILP) is one of the most active available approaches for locally advanced soft tissue sarcomas (STS) of the limbs. The aim of this study was to investigate the anticancer activity of a novel drug regimen including doxorubicin (DXR) and low-dose TNF-alpha. METHODS: HILP with low-dose TNF-alpha (1 mg) and DXR (8.5 mg/L of limb volume) was given to 21 patients with limb-threatening STS: 14 had primary and 7 had recurrent STS, most of which were high grade (grade 1, n = 3; grade 2, n = 6; grade 3, n = 12). Resection of the tumor remnant was performed 6 to 8 weeks after HILP. TNF-alpha concentrations in plasma and perfusate were measured throughout perfusion. RESULTS: A major tumor response was observed at histology and clinical evaluation in 90% and 62% of patients, respectively. After a median follow-up of 30 months, limb salvage and local disease control were achieved in 71% and 81% of cases, respectively. Fourteen patients had moderate regional toxicity, which was resolved in all cases. One patient had severe limb toxicity, which did not require amputation. Systemic side effects were minimal, and there were no postoperative deaths. The perfusate/plasma area under the curve ratio for TNF-alpha was 56. CONCLUSIONS: HILP with low-dose TNF-alpha and DXR seems to be an active neoadjuvant drug regimen against limb-threatening STS. This therapeutic approach can achieve high limb-sparing surgery rates with acceptable local and negligible systemic toxicity.

Original languageEnglish
Pages (from-to)398-405
Number of pages8
JournalAnnals of Surgical Oncology
Volume12
Issue number5
Publication statusPublished - May 2005

ASJC Scopus subject areas

  • Surgery
  • Oncology

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