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Vol. 100. Issue 7.
Pages 571-585 (September 2009)
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Vol. 100. Issue 7.
Pages 571-585 (September 2009)
Original articles
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Experience in the Treatment of Cutaneous In-Transit Melanoma Metastases and Satellitosis With Intralesional Interleukin-2
Esperiencia en el Tratamiento de Satelitosis y Metástasis Cutáneas en Tránsuito de Melanoma con Interleucina 2 Intralesional
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L.A. Dehesa, J. Vilar-Alejo, P. Valerón-Almazán, G. Carretero
Corresponding author
gcarher@gobiernodecanarias.org

Correspondence: Servicio de Dermatología. Hospital Universitario de Gran Canaria Dr. Negrín. Barranco de La Ballena, s/n. 35012 Las Palmas de Gran Canaria, Spain.
Servicio de Dermatología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
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Article information
Abstract
Introduction

Although metastatic melanoma has a poor prognosis, cutaneous metastases represent a special case given their ready accessibility, making it possible for dermatologists to apply local treatment. We report our experience with intralesional treatment with interleukin (IL) 2 in 7 patients with cutaneous metastases from malignant melanoma.

Material and methods

A total of 244 lesions in 7 patients with satellitosis and/or cutaneous metastases from malignant melanoma were treated with intralesional IL-2 twice a week. The maximum dose in each patient ranged from 3 to 18 million units per session, according to the number and size of lesions.

Results

Complete or partial remission was achieved in almost all lesions (95.9% and 3.7%, respectively). Only 1 lesion (0.4%)—the largest and located subcutaneously—did not respond to intralesional treatment and required alcoholization and subsequent surgical removal to achieve cure. All partial responses occurred in subcutaneous lesions larger than 2 cm. Treatment was well tolerated with only a few mild side effects (grade 1-2).

Conclusions

IL-2 may be an effective and well-tolerated treatment option in patients with satellitosis and cutaneous metastases from melanoma. Lesions smaller than 2 cm and located in the epidermis or superficial dermis respond better than those larger than 2 cm or located in the subcutaneous cellular tissue. More studies are necessary to establish appropriate doses and regimens.

Key words:
interleukin 2
malignant melanoma
cutaneous metastasis
intralesional therapy
Resumen
Introducción

A pesar del mal pronóstico del melanoma metastásico, las metástasis cutáneas constituyen un grupo especial por su fácil accesibilidad que lo hace susceptible al abordaje local por parte del dermatólogo. Describimos nuestra experiencia de tratamiento intralesional con interleucina 2 (IL-2) en 7 pacientes con metástasis cutáneas de melanoma maligno.

Material y métodos

Un total de 244 lesiones en 7 pacientes con satelitosis y/o metástasis cutáneas de melanoma maligno han sido tratadas con IL-2 intralesional administrada dos veces a la semana. Las dosis máximas por pacientes variaron entre los 3 y 18 millones de unidades/sesión, en función del número y tamaño de las lesiones.

Resultados

Se han obtenido remisiones completas (95,9%) o parciales (3,7%) en la gran mayoría de lesiones tratadas, una sola lesión (0,4%), de localización subcutánea y de mayor tamaño, no respondió al tratamiento intralesional y precisó de alcoholización y posterior extirpación quirúrgica para su resolución. Todas las respuestas parciales se observaron en lesiones de localización subcutánea y mayores de 2 cm. El tratamiento fue bien tolerado, con escasos efectos secundarios de intensidad leve (grado 1-2).

Conclusiones

La IL-2 puede ser una buena opción para el tratamiento de pacientes con satelitosis y metástasis cutáneas de melanoma con elevada eficacia y escasos efectos secundarios. Las lesiones menores de 2 cm y localizadas en epidermis o dermis superficial responden mejor que las mayores de 2 cm o localizadas en el tejido celular subcutáneo. Son necesarios más estudios para establecer las dosis y pautas de tratamiento adecuadas.

Palabras clave:
interleucina 2
melanoma maligno
metástasis cutáneas
terapia intralesional
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References
[1.]
C.M. Balch, A.C. Buzaid, S.J. Soong, M.B. Atkins, N. Cascinelli, D.G. Coit, et al.
Final Version of the American Joint Committee on Cancer stating system for cutaneous melanoma.
J Clin Oncol, 19 (2001), pp. 3635-3648
[2.]
C.M. Balch, S.J. Soong, M.B. Atkins, A.C. Buzaid, N. Cascinelli, D.G. Coit, et al.
An evidence-based staging system for cutaneous melanoma.
CA Cancer J Clin, 54 (2004), pp. 131-149
[3.]
P. Radny, U.M. Caroll, J. Bauer, T. Paul, C. Schlegel, T.K. Eigentler, et al.
Phase II trial of intralesional therapy with interleukin- 2 in soft-tissue melanoma metastases.
Br J Cancer, 89 (2003), pp. 1620-1626
[4.]
A.C. Buzaid, M.I. Ross, C.M. Balch, S. Soong, W.H. McCarthy, L. Tinoco, et al.
Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system.
J Clin Oncol, 15 (1997), pp. 1039-1051
[5.]
L. Kretscher, K.P. Preufer, C. Neumann.
Locoregional cutaneous metastasis in patients with therapeutic lymph node dissection for malignant melanoma: risk factors and prognostic impact.
Melanoma Res, 12 (2002), pp. 499-504
[6.]
C.R. Rossi, M. Foletto, S. Mocellin, P. Pilati, M. Lise.
Hyperthermic isolated limb perfusion with low-dose tumor necrosis factor-alpha and melphalan for bulky in-transit melanoma metastases.
Ann Surg Oncol, 11 (2004), pp. 173-177
[7.]
A.M. Eggermont.
Treatment of melanoma intransit metastases confined to the limb.
Cancer Surveys, 26 (1996), pp. 335-349
[8.]
J.H. De Wilt, J.F. Thompson.
Is there a role for isolated limb perfusion with tumor necrosis factor in patients with melanoma?.
Ann Surg Oncol, 11 (2004), pp. 119-121
[9.]
D.J. Grünhagen, B. van Etten, F. Brunstein, W.J. Graveland, A.N. van Geel, J.H. de Wilt, et al.
Efficacy of repeat isolated limb perfusions with tumor necrosis factor alpha and melphalan for multiple in-transit metastases in patients with prior isolated limb perfusion failure.
Ann Surg Oncol, 12 (2005), pp. 609-615
[10.]
D.J. Grünhagen, F. Brusntein, W.J. Graveland, A.N. van Geel, J.H. de Wilt, A.M. Eggermont.
One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases.
Ann Surg, 240 (2004), pp. 939-948
[11.]
L.M. Jost, S. Jelic, G. Purkalne.
ESMO minimum clinical recommendations for diagnosis, treatment and follow-up of cutaneous malignant melanoma.
Ann Oncol, 16 (2005), pp. 66-68
[12.]
D.A. Morgan, F.W. Ruscett, R. Gallo.
Selective in vitro growth of T lymphocytes from normal human bone marrows.
Science, 193 (1976), pp. 1007-1008
[13.]
T. Taniguchi, H. Matsui, T. Fujita, C. Takaoka, N. Kashima, R. Yoshimoto, et al.
Structure and expression of a cloned cDNA for human interleukin-2.
Nature, 302 (1983), pp. 305-310
[14.]
T.A. Waldmann.
The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design.
Nat Rev Immunol, 6 (2006), pp. 595-601
[15.]
A.A. Tarhini, S.S. Agarwala.
Interleukin-2 for the treatment of melanoma.
Curr Opin Investig Drugs, 6 (2005), pp. 1234-1239
[16.]
A.K. Abbas, A.H. Lichtman.
Inmunología celular y molecular.
2.a ed., Elsevier España, (2004),
[17.]
J.W. Eklund, T.M. Kuzel.
A review of recent findings involving interleukin-2-based cancer therapy.
Curr Opin Oncol, 16 (2004), pp. 542-546
[18.]
S.A. Rosemberg, J.C. Yang, S.L. Topalian, D.J. Schwartzentruber, J.S. Weber, D.R. Parkinson, et al.
Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin-2.
JAMA, 271 (1994), pp. 907-913
[19.]
E. Huland, H. Heinzer, H. Huland, R. Yung.
Overview of interleukin-2 inhalation therapy.
Cancer J Sci Am, 6 (2000), pp. S104-S112
[20.]
C. Pizzi, M. Caraglia, M. Cianciulli, A. Fabbrocini, A. Libroia, E. Matano, et al.
Low-dose recombinant IL-2 induces psychological changes: monitoring by Minnesota Multiphasic Personality Inventory (MMPI).
Anticancer Res, 22 (2002), pp. 727-732
[21.]
A. Trotti, A.D. Colevas, A. Setser, V. Rusch, D. Jaques, V. Budach, et al.
CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment.
Semen Radiat Oncol, 13 (2003), pp. 176-181
[22.]
K.U. Schallreuter, C. Levenig, J. Berger.
Vitiligo and cutaneous melanoma.
Dermatologica, 183 (1991), pp. 239-245
[23.]
J.C. Bystryn, D. Rigel, Rj. Friedman, A. Kopf.
Prognostic significance of hypopigmentation in malignant melanoma.
Arch Dermatol, 123 (1987), pp. 1053-1055
[24.]
S. Rodríguez-Cuevas, A. López-Chavira, G. Zepeda del Río, I. Cuadra-García, J. Fernández-Díez.
Prognostic significance of cutaneous depigmentation in Mexican patients with malignant melanoma.
Arch Med Res, 29 (1998), pp. 155-158
[25.]
S.A. Rosenberg, D.E. White.
Vitiligo in patients with melanoma: normal tissue antigens can be targets for cancer immunotherapy.
J Immunother Emphasis Tumor Immunol, 19 (1996), pp. 81-84
[26.]
H. Gogas, J. Ioannovich, U. Dafni, C. Stavropoulou-Giokas, K. Frangia, D. Tsoutsos, et al.
Prognostic significance of autoimmunity during treatment of melanoma with interferon.
N Engl J Med, 354 (2006), pp. 709-718
[27.]
F.A. Le Gal, M.F. Avril, J. Bosq, P. Lefebvre, J.C. Deschemin, M. Andrieu, et al.
Direct evidence to support the role of antigen-specific CD8(+) T cells in melanoma-associated vitiligo.
J Invest Dermatol Symp Proc, 117 (2001), pp. 1464-1470
[28.]
P.D. Boasberg, D.S.B. Hoon, L.D. Piro, M.A. Martin, A. Fujimoto, T.S. Kristedja, et al.
Enhanced survival associated with vitiligo expression during maintenance biotherapy for metastatic melanoma.
J Invest Dermatol, 126 (2006), pp. 2658-2663
[29.]
C. Jackaman, C.S. Bundell, B.F. Kinnear, A.M. Smith, P. Filion, D. van Hagen, et al.
IL-2 intratumoral immunotherapy enhances CD8+ T cells that mediate destruction of tumor cells and tumor-associated vasculature: a novel mechanism for IL-2.
Immunol, 171 (2003), pp. 5051-5063
[30.]
E. Chang, S.A. Rosenberg.
Patients with melanoma metastases at cutaneous and subcutaneous sites are highly susceptible to interleukin-2-based therapy.
J Immunother, 24 (2001), pp. 88-90
[31.]
A.H. Enk, D. Nashan, A. Rubben, J. Knop.
High dose inhalation interleukin-2 therapy for lung metastases in patients with malignant melanoma.
Cancer, 9 (2000), pp. 2042-2046
[32.]
G.V. Masucci, E. Mansson-Brahme, B. Ragnarsson-Olding, B. Nilsson, G. Wagenius, J. Hansson.
Alternating chemoimmunotherapy with temozolomide and low-dose interleukin- 2 in patients with metastatic melanoma.
Melanoma Res, 16 (2006), pp. 357-363
[33.]
S.J. O’Day, P.D. Boasberg, L. Piro, T.S. Kristedja, H.J. Wang, T.M. Martin, et al.
Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophagecolony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy.
Clin Cancer Res, 8 (2002), pp. 2775-2781
[34.]
G.C. De Gast, D. Batchelor, M.J. Kersten, F.A. Vyth-Dreese, J. Sein, W.F. van de Kasteele, et al.
Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFN alpha in patients with metastatic melanoma.
Br J Cancer, 88 (2003), pp. 175-180
[35.]
M. González Cao, J. Malvehy, R. Martí, C. Conill, M. Sánchez, M. Martin, et al.
Biochemotherapy with temozolomide, cisplatin, vinblastine, subcutaneous interleukin-2 and interferon- alpha in patients with metastatic melanoma.
[36.]
D.S. Green, A.G. Bodman-Smith, A.D. Dalgleish, M.D. Fischer.
Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma.
Br J Dermatol, 156 (2007), pp. 337-345
[37.]
D.S. Green, N. Dalgleish, N. Belonwu, M.D. Ficher, M.D. Bodman-Smith.
Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma.
Br J Dermatol, 159 (2008), pp. 606-614
Copyright © 2009. Academia Española de Dermatología y Venereología and Elsevier España, S.L.
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