Annals of Oncology Advance Access originally published online on June 1, 2005
Annals of Oncology 2005 16(7):1061-1068; doi:10.1093/annonc/mdi229
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2005 European Society for Medical Oncology
Limb salvage with isolated perfusion for soft tissue sarcoma: could less TNF-
be better?
Departments of 1 Surgery, 2 Public Health, 5 Radiotherapy, 6 Radiology, 7 Pathology, 8 Nuclear Medicine and 9 Medical Oncology, Institut Gustave Roussy, Villejuif, France; 3 Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 4 Department of Surgery, Institut Bergonié, Bordeaux, France; 10 Department of Medical Oncology, Centre Léon Bérard, Lyon, France
* Correspondence to: Dr S. Bonvalot, Department of Surgery, Institut Gustave Roussy, 39 rue Camille, Desmoulins, 94805 Villejuif Cedex, France. Tel: +33-1-42-11-43-83; Fax: +33-1-42-11-52-56; Email: bonvalot{at}igr.fr
Background: The optimal dose of TNF-
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-: 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-. 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- doses tested, there was no dose effect detected for the objective tumour response, but systemic toxicity was significantly correlated with higher TNF- doses. Efficacy and safety of low-dose TNF- could greatly facilitate ILP procedures in the near future.
Key words:
isolated limb perfusion, soft tissue sarcoma, TNF-
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Muret, M. Yacoub, P. Terrier, F. Drusch, A. Laplanche, C. Gaudin, C. Richon, C. Le Pechoux, A. Le Cesne, F. J. Lejeune, et al. p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-{alpha} and melphalan Ann. Onc., April 1, 2008; 19(4): 793 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hohenberger and W. M. Wysocki Neoadjuvant Treatment of Locally Advanced Soft Tissue Sarcoma of the Limbs: Which Treatment to Choose? Oncologist, February 1, 2008; 13(2): 175 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W.T. Pisters, B. O'Sullivan, and R. G. Maki Evidence-Based Recommendations for Local Therapy for Soft Tissue Sarcomas J. Clin. Oncol., March 10, 2007; 25(8): 1003 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Lassau, M. Lamuraglia, L. Chami, J. Leclere, S. Bonvalot, P. Terrier, A. Roche, and A. Le Cesne Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography. Am. J. Roentgenol., November 1, 2006; 187(5): 1267 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. van Horssen, T. L. M. ten Hagen, and A. M. M. Eggermont TNF-{alpha} in Cancer Treatment: Molecular Insights, Antitumor Effects, and Clinical Utility. Oncologist, April 1, 2006; 11(4): 397 - 408. [Abstract] [Full Text] [PDF]
|
|