TNF-based isolated limb perfusion followed by consolidation biotherapy with systemic low-dose interferon alpha 2b in patients with in-transit melanoma metastases

A pilot trial

Carlo Riccardo Rossi, Francesco Russano, Simone Mocellin, Vanna Chiarion-Sileni, Mirto Foletto, Pierluigi Pilati, Luca G. Campana, Antonio Zanon, Gian Franco Picchi, Mario Lise, Donato Nitti

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Tumor necrosis factor (TNF)-based isolated limb perfusion (ILP) yields high tumor response rates in patients with in-transit melanoma metastases. However, most patients will ultimately experience disease recurrence. The aim of this pilot study was to test the hypothesis that systemic low-dose interferon α-2b (LDI) might consolidate the therapeutic effect of ILP. Methods: A total of 12 patients with in-transit melanoma metastases not amenable to surgical excision were given LDI subcutaneously (3 million IU/day, 7 days/week for 12 months) after TNF-based ILP (TNF 1 mg + melphalan (L-PAM) 10 mg/L) (group A). The clinical outcome of these patients was historically compared with that of 19 patients with similar anthropometric and disease characteristics who underwent TNF-based ILP alone (group B). Results: In group A, LDI was well tolerated, only grade 2 systemic toxicity being recorded in 50% of patients. The progression-free survival analysis showed a statistically significant advantage for group A patients as compared with group B (median time to progression: 26 and 17 months, respectively; log-rank test P-value: 0.037). This survival benefit was confirmed at multivariate analysis, where treatment was the only prognostic factor retained by the prediction model. The analysis of the risk of disease progression over time suggested that this survival benefit appears to vanish after LDI discontinuation, which further strengthens the hypothesis that LDI might consolidate the therapeutic effect of TNF-based ILP. Conclusions: These preliminary findings support the conduction of larger trials to formally assess the ability of LDI to improve the clinical outcome of melanoma patients with in-transit metastases undergoing TNF-based ILP.

Original languageEnglish
Pages (from-to)1218-1223
Number of pages6
JournalAnnals of Surgical Oncology
Volume15
Issue number4
DOIs
Publication statusPublished - Apr 2008

Fingerprint

interferon alfa-2b
Biological Therapy
Melanoma
Extremities
Tumor Necrosis Factor-alpha
Perfusion
Interferons
Neoplasm Metastasis
Melphalan
Therapeutic Uses
Survival
Survival Analysis

Keywords

  • Interferon-alpha (IFNα)
  • Isolated limb perfusion
  • Melanoma
  • Tumor necrosis factor (TNF)

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

TNF-based isolated limb perfusion followed by consolidation biotherapy with systemic low-dose interferon alpha 2b in patients with in-transit melanoma metastases : A pilot trial. / Rossi, Carlo Riccardo; Russano, Francesco; Mocellin, Simone; Chiarion-Sileni, Vanna; Foletto, Mirto; Pilati, Pierluigi; Campana, Luca G.; Zanon, Antonio; Picchi, Gian Franco; Lise, Mario; Nitti, Donato.

In: Annals of Surgical Oncology, Vol. 15, No. 4, 04.2008, p. 1218-1223.

Research output: Contribution to journalArticle

Rossi, Carlo Riccardo ; Russano, Francesco ; Mocellin, Simone ; Chiarion-Sileni, Vanna ; Foletto, Mirto ; Pilati, Pierluigi ; Campana, Luca G. ; Zanon, Antonio ; Picchi, Gian Franco ; Lise, Mario ; Nitti, Donato. / TNF-based isolated limb perfusion followed by consolidation biotherapy with systemic low-dose interferon alpha 2b in patients with in-transit melanoma metastases : A pilot trial. In: Annals of Surgical Oncology. 2008 ; Vol. 15, No. 4. pp. 1218-1223.
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abstract = "Background: Tumor necrosis factor (TNF)-based isolated limb perfusion (ILP) yields high tumor response rates in patients with in-transit melanoma metastases. However, most patients will ultimately experience disease recurrence. The aim of this pilot study was to test the hypothesis that systemic low-dose interferon α-2b (LDI) might consolidate the therapeutic effect of ILP. Methods: A total of 12 patients with in-transit melanoma metastases not amenable to surgical excision were given LDI subcutaneously (3 million IU/day, 7 days/week for 12 months) after TNF-based ILP (TNF 1 mg + melphalan (L-PAM) 10 mg/L) (group A). The clinical outcome of these patients was historically compared with that of 19 patients with similar anthropometric and disease characteristics who underwent TNF-based ILP alone (group B). Results: In group A, LDI was well tolerated, only grade 2 systemic toxicity being recorded in 50{\%} of patients. The progression-free survival analysis showed a statistically significant advantage for group A patients as compared with group B (median time to progression: 26 and 17 months, respectively; log-rank test P-value: 0.037). This survival benefit was confirmed at multivariate analysis, where treatment was the only prognostic factor retained by the prediction model. The analysis of the risk of disease progression over time suggested that this survival benefit appears to vanish after LDI discontinuation, which further strengthens the hypothesis that LDI might consolidate the therapeutic effect of TNF-based ILP. Conclusions: These preliminary findings support the conduction of larger trials to formally assess the ability of LDI to improve the clinical outcome of melanoma patients with in-transit metastases undergoing TNF-based ILP.",
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T1 - TNF-based isolated limb perfusion followed by consolidation biotherapy with systemic low-dose interferon alpha 2b in patients with in-transit melanoma metastases

T2 - A pilot trial

AU - Rossi, Carlo Riccardo

AU - Russano, Francesco

AU - Mocellin, Simone

AU - Chiarion-Sileni, Vanna

AU - Foletto, Mirto

AU - Pilati, Pierluigi

AU - Campana, Luca G.

AU - Zanon, Antonio

AU - Picchi, Gian Franco

AU - Lise, Mario

AU - Nitti, Donato

PY - 2008/4

Y1 - 2008/4

N2 - Background: Tumor necrosis factor (TNF)-based isolated limb perfusion (ILP) yields high tumor response rates in patients with in-transit melanoma metastases. However, most patients will ultimately experience disease recurrence. The aim of this pilot study was to test the hypothesis that systemic low-dose interferon α-2b (LDI) might consolidate the therapeutic effect of ILP. Methods: A total of 12 patients with in-transit melanoma metastases not amenable to surgical excision were given LDI subcutaneously (3 million IU/day, 7 days/week for 12 months) after TNF-based ILP (TNF 1 mg + melphalan (L-PAM) 10 mg/L) (group A). The clinical outcome of these patients was historically compared with that of 19 patients with similar anthropometric and disease characteristics who underwent TNF-based ILP alone (group B). Results: In group A, LDI was well tolerated, only grade 2 systemic toxicity being recorded in 50% of patients. The progression-free survival analysis showed a statistically significant advantage for group A patients as compared with group B (median time to progression: 26 and 17 months, respectively; log-rank test P-value: 0.037). This survival benefit was confirmed at multivariate analysis, where treatment was the only prognostic factor retained by the prediction model. The analysis of the risk of disease progression over time suggested that this survival benefit appears to vanish after LDI discontinuation, which further strengthens the hypothesis that LDI might consolidate the therapeutic effect of TNF-based ILP. Conclusions: These preliminary findings support the conduction of larger trials to formally assess the ability of LDI to improve the clinical outcome of melanoma patients with in-transit metastases undergoing TNF-based ILP.

AB - Background: Tumor necrosis factor (TNF)-based isolated limb perfusion (ILP) yields high tumor response rates in patients with in-transit melanoma metastases. However, most patients will ultimately experience disease recurrence. The aim of this pilot study was to test the hypothesis that systemic low-dose interferon α-2b (LDI) might consolidate the therapeutic effect of ILP. Methods: A total of 12 patients with in-transit melanoma metastases not amenable to surgical excision were given LDI subcutaneously (3 million IU/day, 7 days/week for 12 months) after TNF-based ILP (TNF 1 mg + melphalan (L-PAM) 10 mg/L) (group A). The clinical outcome of these patients was historically compared with that of 19 patients with similar anthropometric and disease characteristics who underwent TNF-based ILP alone (group B). Results: In group A, LDI was well tolerated, only grade 2 systemic toxicity being recorded in 50% of patients. The progression-free survival analysis showed a statistically significant advantage for group A patients as compared with group B (median time to progression: 26 and 17 months, respectively; log-rank test P-value: 0.037). This survival benefit was confirmed at multivariate analysis, where treatment was the only prognostic factor retained by the prediction model. The analysis of the risk of disease progression over time suggested that this survival benefit appears to vanish after LDI discontinuation, which further strengthens the hypothesis that LDI might consolidate the therapeutic effect of TNF-based ILP. Conclusions: These preliminary findings support the conduction of larger trials to formally assess the ability of LDI to improve the clinical outcome of melanoma patients with in-transit metastases undergoing TNF-based ILP.

KW - Interferon-alpha (IFNα)

KW - Isolated limb perfusion

KW - Melanoma

KW - Tumor necrosis factor (TNF)

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