Limb salvage with isolated perfusion for soft tissue sarcoma: Could less TNF-α be better?

S. Bonvalot, A. Laplanche, F. Lejeune, E. Stoeckle, C. Le Páchoux, D. Vanel, P. Terrier, J. Lumbroso, M. Ricard, G. Antoni, A. Cavalcanti, C. Robert, N. Lassau, J. Y. Blay, A. Le Cesne

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    Abstract

    Background: The optimal dose of TNF-α delivered by isolated limb perfusion (ILP) in patients with locally advanced soft tissue sarcoma is still unknown. Patients and methods: Randomised phase II trial comparing hyperthermic ILP (38-40°) with melphalan and one of the four assigned doses of TNF-α: 0.5 mg, 1 mg, 2 mg, and 3/4 mg upper/ lower limb. The main end point was objective tumour response on MRI. Secondary end points were histological response, rate of amputation and toxicity. Resection of the remnant tumour was performed 2-3 months after ILP. The sample size was calculated assuming a linear increase of 10% in the objective response rates between each dose level group. Results: One hundred patients (25 per arm) were included. Thirteen per cent of patients had a systemic leakage with a cardiac toxicity in six patients correlated with high doses of TNF-α. Objective tumour responses were: 68%, 56%, 72% and 64% in the 0.5 mg, 1 mg, 2 mg and 3 or 4 mg arms, respectively (NS). Sixteen per cent of patients were not operated, 71% had a conservative surgery and 13% were amputated with no difference between the groups. With a median follow-up of 24 months, the 2 year overall and disease-free survival rates (95% CI) were 82% (73% to 89%) and 49% (39% to 59%), respectively. Conclusion: At the range of TNF-α doses tested, there was no dose effect detected for the objective tumour response, but systemic toxicity was significantly correlated with higher TNF-α doses. Efficacy and safety of low-dose TNF-α could greatly facilitate ILP procedures in the near future.

    Original languageEnglish
    Pages (from-to)1061-1068
    Number of pages8
    JournalAnnals of Oncology
    Volume16
    Issue number7
    DOIs
    Publication statusPublished - 1 Jan 2005

    Keywords

    • Isolated limb perfusion
    • Soft tissue sarcoma
    • TNF-α

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