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Inicio Revista Española de Cirugía Ortopédica y Traumatología Perfusión de extremidad aislada en sarcomas de partes blandas irresecables: un ...
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Vol. 48. Núm. 1.
Páginas 57-64 (enero 2004)
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Vol. 48. Núm. 1.
Páginas 57-64 (enero 2004)
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Perfusión de extremidad aislada en sarcomas de partes blandas irresecables: un nuevo estándar
Isolated limb perfusion for unresectable soft-tissue sarcomas: a new standard
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4247
E. Calvoa,
Autor para correspondencia
ecalvo@idd.org

Correspondencia: Institute for Drug Development. Cancer Therapy and Research Center. 7979 Wurzback, Zeller building, 4th floor, Room #z414H. San Antonio, texas 78229, USA.
, R. Arcasb, A. Brugarolasa, A. Crespoc, T. Ten-Hagend, A. Eggermontd
a Departamento de Oncología. Hospital San Jaime. Torrevieja. Alicante. España
b Departamento de Cirugía Cardiovascular y Torácica. Hospital San Jaime. Torrevieja. Alicante. España
c Departamento de Medicina Nuclear. Hospital San Jaime. Torrevieja. Alicante. España
d Department of Surgical Oncology. Daniel den Hoed Cancer Center. Erasmus University Medical Center. Rotterdam. The Netherlands
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La perfusion de extremidad aislada (PEA) con solo melfalan no ha mostrado eficacia en el tratamiento de sarcomas de partes blandas (SPB) irresecables de extremidad. Esta situacion se ha visto modificada con la aparicion del factor de necrosis tumoral-α (TNF), farmaco que ataca los vasos tumorales y aumenta de tres a seis veces la captacion selectiva de otros medicamentos por el tumor. Durante los ultimos diez anos, diversos estudios han demostrado que la combinacion de TNF y melfalan, administrada mediante PEA, produce un efecto antitumoral espectacular. En la actualidad es el tratamiento estandar para los pacientes con SPB de extremidad irresecables y subsidiarios de amputacion fisica o funcional del miembro afecto, ya que en mas del 70% de los casos logra una disminucion de la tumoracion suficiente como para realizar posteriormente una cirugia de exeresis del residuo tumoral con conservacion fisica y funcional de la extremidad.

Palabras clave:
perfusión de extremidad aislada
sarcomas de partes blandas irresecables
nuevo estándar

Isolated limb perfusion (ILP) with melphalan alone is not effective in the therapy of unresectable soft-tissue sarcomas (STS) of the extremities. Tumor necrosis factor-á (TNF), a drug that destroys tumor vessels and enhances tumor drug uptake three-fold to six-fold, has definitely changed this situation. In the last decade, investigations have shown that ILP with TNF and melphalan has impressive antitumoral effects. Nowadays, it is considered the standard treatment for unresectable limb STS, in which physical or functional amputation is advocated, since major tumor remission is achieved in more than 70% of cases, making surgical excision of the remnant tumor with physical and functional limb preservation possible.

Key words:
isolated limb perfusion
unresectable soft-tissue sarcomas
new standard
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Bibliografía
[1.]
M.F. Brennan, K.M. Alektiar, R.G. Maki.
Soft tissue sarcoma.
Cancer: Principles and Practice of Oncology, 6th,
[2.]
D.G. Creech.
Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit.
Ann Surg, 4 (1958), pp. 616-632
[3.]
C. Benckhuijsen, B.B.R. Kroon, A.N. van Geel, J. Wieberdink.
Regional perfusion treatment with melphalan for melanoma in a limb: an evaluation of drug kinetics.
Eur J Surg Oncol, 14 (1988), pp. 157-163
[4.]
K. Wieberdink, C. Benckhuyjsen, R.P. Braat, E.A. van Slooten, G.A. Oldhios.
Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions.
Eur J Cancer Clin Oncol, 18 (1982), pp. 905-910
[5.]
J.M. Klaase, B.B.R. Kroon, A.N. van Geel, A.M.M. Eggermont, H.R. Franklin.
Systemic leakage during isolated limb perfusion for melanoma.
Br J Surg, 80 (1993), pp. 1124-1126
[6.]
B.C. Vrouenraets, B.B. Kroon, A.C. Ogilvie, A.N. van Geel, O.E. Nieweg, A.J. Swaak, et al.
Absence of severe systemic toxicity after leakage-controlled isolated limb perfusion with tumor necrosis factor-alpha and melphalan.
Ann Surg Oncol, 6 (1999), pp. 405-412
[7.]
G. Omlor, G. Gross, K.W. Ecker, I. Burger, G. Feifel.
Optimization of isolated hyperthermic limb perfusion.
World J Surg, 16 (1992), pp. 1117-1119
[8.]
R. Cavaliere, E.C. Ciocatto, B.C. Giovanella, C. Heidelberger, R.O. Johnson, M. Margottini, et al.
Selective heat sensitivity of cancer cells. Biochemical and clinical studies.
Cancer, 20 (1967), pp. 1351-1381
[9.]
O. Dahl, O. Mella.
Hyperthermia and chemotherapeutic agents.
An Introduction to the Practical Aspects of Hyperthermia, pp. 108-142
[10.]
J. Clark, A.J. Grabs, P.G. Parsons, B.M. Smithers, R.S. Addison, M.S. Roberts.
Melphalan uptake, hyperthermic synergism and drug resistance in a human cell culture model for the isolated limb perfusion of melanoma.
Melanoma Res, 4 (1994), pp. 365-370
[11.]
J.M. Klaase, B.B.R. Kroon, A.N. van Geel, A.M.M. Eggermont, H.R. Franklin, A.A. Hart.
Prognostic factors for tumor response and limb recurrence-free interval in patients with advanced melanoma of the limbs treated with regional isolated perfusion with melphalan.
Surgery, 115 (1994), pp. 39-45
[12.]
R.D. Rosin, G. Westbury.
Isolated limb perfusion for malignant melanoma.
Practitioner, 224 (1980), pp. 1031-1036
[13.]
F.J. Lejeune, T. Deloof, P. Ewalenko, J. Fruhling, M. Jabri, M. Mathieu, et al.
Objective regression of unexcised melanoma in-transit metastases after hyperthermic isolation perfusion of the limbs with melphalan.
Recent Results Cancer Res, 86 (1983), pp. 268-276
[14.]
D.R. Minor, R.E. Allen, D. Alberts, Y.M. Peng, G. Tardelli, J. Hutchinson.
A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma.
Cancer, 55 (1985), pp. 2638-2644
[15.]
A.I. Skene, A.S. Bulman, T.R. Williams, J.M. Thomas, G. Westbury.
Hyperthermic isolated perfusion with melphalan in the treatment of advanced malignant melanoma of the lower limb.
Br J Surg, 77 (1990), pp. 765-767
[16.]
C. Kettelhack, T. Kraus, T. Hupp, M. Manner, P.M. Schlag.
Hyperthermic limb perfusion for malignant melanoma and soft tissue sarcoma.
Eur J Surg Oncol, 16 (1990), pp. 370-375
[17.]
J.M. Klaase, B.B.R. Kroon, A.M.M. Eggermont, A.N. van Geel, K.H. Schraffordt, J. Oldhoff, et al.
A retrospective comparative study evaluating the results of mild hyperthermic versus controlled normothermic perfusion for recurrent melanoma of the extremities.
Eur J Cancer, 31A (1995), pp. 58-63
[18.]
M. Vaglini, S. Andreola, A. Attili, F. Belli, R. Marolda, M. Nava, et al.
Hyperthermic antiblastic perfusion in the treatment of cancer of the extremities.
Tumori, 71 (1985), pp. 355-359
[19.]
F.K. Storm, D.L. Morton.
Value of therapeutic hyperthermic limb perfusion in advanced recurrent melanoma of the lower extremity.
Am J Surg, 150 (1985), pp. 32-35
[20.]
P.J. Bryant, G.A. Balderson, P. Mead, W.S. Egerton.
Hyperthermic isolated limb perfusion for malignant melanoma: response and survival.
World J Surg, 19 (1995), pp. 363-368
[21.]
F. Di Filippo, A. Calabro, D. Giannarelli, S. Carlini, F. Cavaliere, F. Moscarelli, et al.
Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblastic perfusion.
Cancer, 63 (1989), pp. 2551-2561
[22.]
B.B.R. Kroon, J.M. Klaase, A.N. van Geel, A.M.M. Eggermont.
Application of hyperthermia in regional isolated perfusion for melanoma of the limbs.
Reg Cancer Treat, 4 (1992), pp. 223-226
[23.]
E.T. Krementz, R.D. Carter, C.M. Sutherland, I. Hutton.
Chemotherapy of sarcomas of the limbs by regional perfusion.
Ann Surg, 185 (1977), pp. 555-564
[24.]
C.M. McBride.
Sarcomas of the limbs. Results of adjuvant chemotherapy using isolation perfusion.
Arch Surg, 109 (1974), pp. 304-308
[25.]
J.S.J. Stehlin, P.D. de Ipolyi, B.C. Giovanella, A.E. Gutierrez, R.F. Anderson.
Soft tissue sarcomas of the extremity. Multidisciplinary therapy employing hyperthermic perfusion.
Am J Surg, 130 (1975), pp. 643-646
[26.]
P.M. Lehti, H.S. Moseley, K. Janoff, K. Stevens, W.S. Fletcher.
Improved survival for soft tissue sarcoma of the extremities by regional hyperthermic perfusion, local excision and radiation therapy.
Surg Gynecol Obstet, 162 (1986), pp. 149-152
[27.]
H.J. Hoekstra, H. Schraffordt Koops, W.M. Molenaar, J. Oldhoff.
Results of isolated regional perfusion in the treatment of malignant soft tissue tumors of the extremities.
Cancer, 60 (1987), pp. 1703-1707
[28.]
R.P. Braat, J. Wieberdink, E. van Slooten, G. Olthuis.
Regional perfusion with adriamycin in soft tissue sarcomas.
Recent Results Cancer Res, 86 (1983), pp. 260-263
[29.]
J.M. Klaase, B.B. Kroon, C. Benckhuijsen, A.N. van Geel, C.E. Albus-Lutter, J. Wieberdink.
Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities.
Cancer, 64 (1989), pp. 616-621
[30.]
C.R. Rossi, A. Vecchiato, M. Foletto, D. Nitti, V. Ninfo, A. Fornasiero, et al.
Phase II study on neoadjuvant hyperthermic-antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas.
Cancer, 73 (1994), pp. 2140-2146
[31.]
F. Di Filippo, A.M. Calabro, A. Cavallari, S. Carlini, G.L. Buttini, F. Moscarelli, et al.
The role of hyperthermic perfusion as a first step in the treatment of soft tissue sarcoma of the extremities.
World J Surg, 12 (1988), pp. 332-339
[32.]
E.A. Carswell, L.J. Old, R.L. Kassel, S. Green, N. Fiore, B. Williamson.
An endotoxin-induced serum factor that causes necrosis of tumors.
Proc Natl Acad Sci USA, 72 (1975), pp. 3666-3670
[33.]
D.R. Spriggs, M.L. Sherman, H. Michie, K.A. Arthur, K. Imamura, D. Wilmore, et al.
Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study.
J Natl Cancer Inst, 80 (1988), pp. 1039-1044
[34.]
A. Asher, J.J. Mule, C.M. Reichert, E. Shiloni, S.A. Rosenberg.
Studies on the anti-tumor efficacy of systemically administered recombinant tumor necrosis factor against several murine tumors in vivo.
J Immunol, 138 (1987), pp. 963-974
[35.]
N. Watanabe, Y. Niitsu, H. Umeno, H. Kuriyama, H. Neda, N. Yamauchi, et al.
Toxic effect of tumor necrosis factor on tumor vasculature in mice.
Cancer Res, 48 (1988), pp. 2179-2183
[36.]
A.M.M. Eggermont, D. Lienard, H. Schraffordt Koops, et al.
Limb salvage by high dose tumor necrosis factor-alpha (TNF), gamma-interferon (IFN) and melphalan isolated limb perfusion (ILP) in patients with irresectable soft tissue sarcomas (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol, 22 (1992), pp. 412
[37.]
A.M.M. Eggermont, K.H. Schraffordt, D. Lienard, B.B.R. Kroon, A.N. van Geel, H.J. Hoekstra, et al.
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.
J Clin Oncol, 14 (1996), pp. 2653-2665
[38.]
A.M.M. Eggermont, H. Schraffordt-Koops, J.M. Klausner, P.M. Schlag, D. Lienard, B.B. Kroon, et al.
Limb Salvage By Isolated Limb Perfusion (ILP) with TNF and Melphalan in Patients with Locally Advanced Soft Tissue Sarcomas: Outcome of 270 ILPs in 246 Patients (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol, (1999),
[39.]
C.R. Rossi, M. Foletto, F. Di Filippo, M. Vaglini, M. Anza, A. Azzarelli, et al.
Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusion.
Cancer, 86 (1999), pp. 1742-1749
[40.]
D.L. Fraker, H.R. Alexander, M. Andrich, S.A. Rosenberg.
Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor, and interferon gamma: results of a tumor necrosis factor dose-escalation study.
J Clin Oncol, 14 (1996), pp. 479-489
[41.]
D. Lienard, A.M.M. Eggermont, H. Schraffordt Koops, B.B.R. Kroon, G. Towse, S. Hiemstra, et al.
Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study.
Melanoma Res, 9 (1999), pp. 491-502
[42.]
A.F. Olieman, D. Lienard, A.M.M. Eggermont, B.B.R. Kroon, F.J. Lejeune, H.J. Hoekstra, et al.
Hyperthermic isolated limb perfusion with tumor necrosis factor alpha, interferon gamma, and melphalan for locally advanced nonmelanoma skin tumors of the extremities: a multicenter study.
Arch Surg, 134 (1999), pp. 303-307
[43.]
J. Bickels, E.R. Manusama, M. Gutman, A.M.M. Eggermont, Y. Kollender, S. Abu-Abid, et al.
Isolated limb perfusion with tumor necrosis factor-alpha and melphalan for unresectable bone sarcomas of the lower extremity.
Eur J Surg Oncol, 25 (1999), pp. 509-514
[44.]
A.M.M. Eggermont, H. Schraffordt Koops, D. Lienard, et al.
Angiographic observations before and after high dose TNF isolated limb perfusion in patients with extremity soft tissue sarcomas.
Eur J Surg Oncol, 20 (1994), pp. 324
[45.]
P.E. Sijens, A.M.M. Eggermont, P.V. van Dijk, M. Oudkerk.
31P magnetic resonance spectroscopy as predictor of clinical response in human extremity sarcomas treated by single dose TNF-alpha + melphalan isolated limb perfusion.
NMR Biomed, 8 (1995), pp. 215-224
[46.]
N. Renard, D. Lienard, L. Lespagnard, A.M.M. Eggermont, R. Heimann, F.J. Lejeune.
Early endothelium activation and polymorphonuclear cell invasion precede specific necrosis of human melanoma and sarcoma treated by intravascular highdose tumor necrosis factor alpha (rTNF alpha).
Int J Cancer, 57 (1994), pp. 656-663
[47.]
N. Renard, P.T. Nooijen, L. Schalkwijk, R.M. de Waal, A.M.M. Eggermont, D. Lienard, et al.
VWF release and platelet aggregation in human melanoma after perfusion with TNF alpha.
J Pathol, 176 (1995), pp. 279-287
[48.]
P.T. Nooijen, A.M.M. Eggermont, L. Schalkwijk, S. Henzen-Logmans, R.M. de Waal, D.J. Ruiter.
Complete response of melanoma-in-transit metastasis after isolated limb perfusion with tumor necrosis factor alpha and melphalan without massive tumor necrosis: a clinical and histopathological study of the delayed-type reaction pattern.
Cancer Res, 58 (1998), pp. 4880-4887
[49.]
E.R. Manusama, P.T. Nooijen, J. Stavast, N.M. Durante, R.L. Marquet, A.M.M. Eggermont.
Synergistic antitumor effect of recombinant human tumor necrosis factor alpha with melphalan in isolated limb perfusion in the rat.
Br J Surg, 83 (1996), pp. 551-555
[50.]
E.R. Manusama, J. Stavast, N.M. Durante, R.L. Marquet, A.M.M. Eggermont.
Isolated limb perfusion with TNF alpha and melphalan in a rat osteosarcoma model: a new anti-tumor approach.
Eur J Surg Oncol, 22 (1996), pp. 152-157
[51.]
M.C. Posner, D. Lienard, F.J. Lejeune, D. Rosenfelder, J. Kirkwood.
Hyperthermic Isolated Limb Perfusion With Tumor Necrosis Factor Alone for Melanoma.
Cancer J Sci Am, 1 (1995), pp. 274
[52.]
P.T. Nooijen, E.R. Manusama, A.M.M. Eggermont, L. Schalkwijk, J. Stavast, R.L. Marquet, et al.
Synergistic effects of TNFalpha and melphalan in an isolated limb perfusion model of rat sarcoma: a histopathological, immunohistochemical and electron microscopical study.
Br J Cancer, 74 (1996), pp. 1908-1915
[53.]
T. Manda, F. Nishigaki, S. Mukumoto, K. Masuda, T. Nakamura, K. Shimomura.
The efficacy of combined treatment with recombinant human tumor necrosis factor-alpha and 5-fluorouracil is dependent on the development of capillaries in tumor.
Eur J Cancer, 26 (1990), pp. 93-99
[54.]
J.J. Mule, A. Asher, J. McIntosh, R. Lafreniere, E. Shiloni, A. Lefor, et al.
Antitumor effect of recombinant tumor necrosis factor-alpha against murine sarcomas at visceral sites: tumor size influences the response to therapy.
Cancer Immunol Immunother, 26 (1988), pp. 202-208
[55.]
J.H. de Wilt, T.L. Ten Hagen, G. de Boeck, S.T. van Tiel, E.A. de Bruijn, A.M.M. Eggermont.
Tumor necrosis factor alpha increases melphalan concentration in tumor tissue after isolated limb perfusion.
Br J Cancer, 82 (2000), pp. 1000-1003
[56.]
Veen van der, J.H. de Wilt, A.M.M. Eggermont, S.T. van Tiel, A.L. Seynhaeve, T.L. Ten Hagen.
TNF-alpha augments intratumoral concentrations of doxorubicin in TNF-alpha-based isolated limb perfusion in rat sarcoma models and enhances antitumor effects.
Br J Cancer, 82 (2000), pp. 973-980
[57.]
C.A. Kristensen, M. Nozue, Y. Boucher, R.K. Jain.
Reduction of interstitial fluid pressure after TNF-alpha treatment of three human melanoma xenografts.
Br J Cancer, 74 (1996), pp. 533-536
[58.]
R.K. Jain.
Barriers to drug delivery in solid tumors.
Sci Am, 271 (1994), pp. 58-65
[59.]
E.R. Manusama, P.T. Nooijen, J. Stavast, J.H. de Wilt, R.L. Marquet, A.M.M. Eggermont.
Assessment of the role of neutrophils on the antitumor effect of TNFalpha in an in vivo isolated limb perfusion model in sarcoma-bearing brown Norway rats.
J Surg Res, 78 (1998), pp. 169-175
[60.]
J.H. de Wilt, E.R. Manusama, S.T. van Tiel, M.G. van Ijken, T.L. Ten Hagen, A.M.M. Eggermont.
Prerequisites for effective isolated limb perfusion using tumor necrosis factor alpha and melphalan in rats.
Br J Cancer, 80 (1999), pp. 161-166
[61.]
S. Hill, W.J. Fawcett, J. Sheldon, N. Soni, T. Williams, J.M. Thomas.
Low-dose tumor necrosis factor alpha and melphalan in hyperthermic isolated limb perfusion.
Br J Surg, 80 (1993), pp. 995-997
[62.]
E.R. Manusama, J.H. de Wilt, T.L. Ten Hagen, R.L. Marquet, A.M.M. Eggermont.
Toxicity and antitumor activity of interferon gamma alone and in combinations with TNFalpha and melphalan in isolated limb perfusion in the BN175 sarcoma tumor model in rats.
Oncol Rep, 6 (1999), pp. 173-177
[63.]
D. Lienard, A.M.M. Eggermont, H. Schraffordt-Koops, B.B.R. Kroon, G. Towse, S. Hiemstra, et al.
Isolated limb perfusion with tumor necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study.
Melanoma Res, 9 (1999), pp. 491-502
[64.]
J.H. de Wilt, E.R. Manusama, B. van Etten, S.T. van Tiel, A.S. Jorna, A.L. Seynhaeve, et al.
Nitric oxide synthase inhibition results in synergistic anti-tumor activity with melphalan and tumor necrosis factor alpha-based isolated limb perfusions.
Br J Cancer, 83 (2000), pp. 1176-1182
[65.]
W.K. de Roos, J.H. de Wilt, M. van der Kaaden, E.R. Manusama, M.W. de Vries, A. Bout, et al.
Isolated limb perfusion for local gene delivery: efficient and targeted adenovirus-mediated gene transfer into soft tissue sarcomas.
Ann Surg, 232 (2000), pp. 814-821
[66.]
J.H. de Wilt, A. Bout, A.M.M. Eggermont, S.T. van Tiel, M.W. de Vries, T.L. Ten Hagen, et al.
Adenovirus-mediated interleukin 3 beta gene transfer by isolated limb perfusion inhibits growth of limb sarcoma in rats.
Hum Gene Ther, 12 (2001), pp. 489-502
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