scholarly journals Isolated Limb Perfusion with Tumor Necrosis Factor Alpha and Melphalan for Locally Advanced Soft Tissue Sarcoma: Three Time Periods at Risk for Amputation

2007 ◽  
Vol 14 (4) ◽  
pp. 1499-1506 ◽  
Author(s):  
Robert J. van Ginkel ◽  
Katja M. J. Thijssens ◽  
Elisabeth Pras ◽  
Winette T. A. van der Graaf ◽  
Albert J. H. Suurmeijer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Necrosis ◽  
Locally Advanced ◽  
Advanced Soft Tissue Sarcoma ◽  
Necrosis Factor Alpha ◽  
Limb Perfusion ◽  
Factor Alpha ◽  
Time Periods ◽  
Necrosis Factor

Treatment of Recurrent Sarcoma of the Extremities by Isolated Limb Perfusion Using Tumor Necrosis Factor Alpha and Melphalan

1996 ◽  
Vol 82 (6) ◽  
pp. 579-584 ◽  
Author(s):  
Mario Santinami ◽  
Marcello Deraco ◽  
Alberto Azzarelli ◽  
Federico Cascinelli ◽  
Arturo Chiti ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Antitumor Activity ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Local Progression ◽  
Limb Perfusion ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background 24-60% of patients with soft tissue sarcoma shows local recurrences after treatment of the primary tumor. The event is associated with a high incidence of macroscopic or microscopic metastases and a poor survival. Our goal is to preserve a patient's functional limb by treating such cases with isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rHu TNF-α) and melphalan, which have demonstrated a potent antitumor activity in vivo and in vitro studies. Methods During the period November 1991 to November 1995, 10 patients with unresectable recurrent soft tissue sarcoma of the limb were treated by ILP at intermediate hyperthermia (40-40.5 °C) with rHu TNF-α and melphalan. Two patients also received recombinant interferon gamma (rIFN-γ) before and during ILP. We used a range of 2-4 mg for rHu TNF-α and 50-100 mg of melphalan. rIFN-γ was administered on days -2 and -1 (15x106 IU) subcutaneously and the same dose was injected in the arterial line during ILP. Results No perioperative surgical complication was observed. Local toxicity was moderate (grade I or II); general toxicity was observed in 6 patients (2 grade I and 4 grade III). Complete response was obtained in 7 cases; 2 patients had a partial response and finally 1 was a nonresponder and showed local progression, which required surgical amputation. Tumor necrosis (observed in 5 cases) was maximal in 4 patients (80-100%) and absent in the patient who had local progression. Conclusions The results we obtained with the treatment of soft tissue sarcoma confirm the efficacy of ILP as a limb-sparing methodology for unresectable recurrences. Furthermore, rHu TNF-α and melphalan confirmed their antitumor activity when associated with hyperthermia. Amputation or disarticulation may be reliable as a second-choice treatment for these patients.

Angiographic response of locally advanced soft-tissue sarcoma following hyperthermic isolated limb perfusion with tumor necrosis factor

1997 ◽  
Vol 4 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Annette F. T. Olieman ◽  
Robert J. van Ginkel ◽  
Harald J. Hoekstra ◽  
Eduard L. Mooyaart ◽  
Willemina M. Molenaar ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Tumor Necrosis Factor ◽  
Soft Tissue Sarcoma ◽  
Tumor Necrosis ◽  
Locally Advanced ◽  
Isolated Limb Perfusion ◽  
Advanced Soft Tissue Sarcoma ◽  
Limb Perfusion ◽  
Necrosis Factor

Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial.

1996 ◽  
Vol 14 (10) ◽  
pp. 2653-2665 ◽  
Author(s):  
A M Eggermont ◽  
H Schraffordt Koops ◽  
D Liénard ◽  
B B Kroon ◽  
A N van Geel ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Tumor Necrosis Factor ◽  
Limb Salvage ◽  
Tumor Necrosis ◽  
Soft Tissue Sarcomas ◽  
Necrosis Factor Alpha ◽  
Limb Perfusion ◽  
Factor Alpha ◽  
Tumor Remnant ◽  
Necrosis Factor

PURPOSE To determine the efficacy of isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) in combination with interferon-gamma (IFN) and melphalan as induction therapy to render tumors resectable and avoid amputation in patients with nonresectable extremity soft tissue sarcomas (STS). PATIENTS AND METHODS Among 55 patients with 30 primary and 25 recurrent sarcomas, there were 48 high-grade and seven grade 1 sarcomas (very large, recurrent, or multiple). The composition of this series of patients is unusual: 13 patients (24%) had multifocal primary sarcomas or multiple recurrent tumors; tumors were very large (median, 18 cm); and nine patients (16%) had known systemic metastases. IFN was administered subcutaneously on the 2 days before ILP with TNF, IFN, and melphalan. A delayed marginal resection of the tumor remnant was usually performed 2 to 3 months after ILP. RESULTS A major tumor response was seen in 87% of patients and rendered the sarcomas resectable in most cases. Clinical response rates were as follows: 10 (18%) completes responses (CRs), 35 (64%) partial responses (PRs), and 10 (18%) no change (NC). Final outcome was defined as follows by clinical and pathologic response: 20 (36%) CRs, 28 (51%) PRs, and seven (13%) NC. Limb salvage was achieved in 84% (follow-up duration, 20+ to 50+ months). In 39 patients, resection of the tumor remnant (n = 31) or of two to eight tumors (n = 8) after ILP was performed; local recurrence developed in five (13%). When no resection was performed (multiple tumors or systemic metastases), local recurrences were frequent (five of 16), but limb salvage was often achieved as patients died of systemic disease. Regional toxicity was limited and systemic toxicity minimal to moderate with no toxic deaths. Histology showed hemorrhagic necrosis; angiographies showed selective destruction of tumor-associated vessels. CONCLUSION ILP with TNF, IFN, and melphalan is a safe and highly effective induction biochemotherapy procedure that can achieve limb salvage in patients with nonresectable extremity STS. TNF is an active anticancer drug in humans in the setting of ILP.

Sign in / Sign up

Export Citation Format

Share Document