Isolated limb perfusion with tumour necrosis factor-α and melphalan for unresectable bone sarcomas of the lower extremity

Bickels, Jacob; Manusama, Eric R.; Gutman, Mordechai; Eggermont, Alexander M.M.; Kollender, Yehuda; Abu-Abid, S.; Geel, A.N. van; Lev-Shlush, D.; Klausner, Joseph M.; Meller, Isaac

doi:10.1053/ejso.1999.0687

Cited by 33 publications

(11 citation statements)

References 28 publications

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“…Limb-sparing surgery was possible in 70% of patients with unresectable bone sarcoma patients. 20 One patient in our series underwent HILP for osteosarcoma and had a good response initially but required a belowknee amputation for multiple local recurrences.…”

Section: Discussionmentioning

confidence: 83%

Hyperthermic Isolated Limb Perfusion for Extremity Sarcomas

Kim

Puleo

Letson³

et al. 2001

Cancer Control

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Section: Discussionmentioning

confidence: 83%

Hyperthermic Isolated Limb Perfusion for Extremity Sarcomas

Kim

Puleo

Letson³

et al. 2001

Cancer Control

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“…In osteosarcoma, the biological response modifier recombinant tumor necrosis factor-a (TNF-a) is the effective agent now in use, preferably in combination with melphalan or another cytostatic agent, with a reported response rate of 77% [7,8]. Melphalan alone in this tumor has no significant effect [8].…”

Section: Discussionmentioning

confidence: 99%

Isolated limb perfusion with melphalan for femoral metastases of breast cancer: Case report

Noorda¹,

Vrouenraets²,

Nieweg³

et al. 2002

Journal of Surgical Oncology

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“…Venous blood from healthy adult volunteers was collected in Na-heparin tubes (Becton Dickinson, Alphen aan den Rijn, the Netherlands). After centrifuging for 20 minutes (1,500 Â g, room temperature), total WBC fraction was collected, and remaining RBC were lysed with lysis buffer [0.83% NH 4 Cl and 10 mmol/L HEPES (pH 7.0)] for 30 minutes at room temperature. After centrifuging for 30 minutes (1,500 rpm, room temperature), the leukocytes were dissolved in HUVEC medium at a concentration of 120 Â 10 4 cells/mL.…”

Section: Methodsmentioning

confidence: 99%

“…We have shown that isolated limb perfusion (ILP) with tumor necrosis factor (TNF)-a and melphalan is associated with excellent antitumor effects against melanoma (1), large soft tissue sarcomas (2,3), and various other tumors in the clinical setting (4)(5)(6). We have previously shown that the basis for the synergy is, on one hand a significant enhancement of tumor-selective melphalan uptake and on the other hand the subsequent complete destruction of tumor vasculature (2, 7).…”

Section: Introductionmentioning

confidence: 99%

Synergistic Antitumor Response of Interleukin 2 with Melphalan in Isolated Limb Perfusion in Soft Tissue Sarcoma–Bearing Rats

et al. 2005

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The cytokine interleukin 2 (IL-2) is a mediator of immune cell activation with some antitumor activity, mainly in renal cell cancer and melanoma. We have previously shown that tumor necrosis factor (TNF)-A has strong synergistic antitumor activity in combination with chemotherapeutics in the isolated limb perfusion (ILP) setting based on a TNF-mediated enhanced tumor-selective uptake of the chemotherapeutic drug followed by a selective destruction of the tumor vasculature. IL-2 can cause vascular leakage and edema and for this reason we examined the antitumor activity of a combined treatment with IL-2 and melphalan in our wellestablished ILP in soft tissue sarcoma-bearing rats (BN175). ILP with either IL-2 or melphalan alone has no antitumor effect, but the combination of IL-2 and melphalan resulted in a strong synergistic tumor response, without any local or systemic toxicity. IL-2 enhanced significantly melphalan uptake in tumor tissue. No signs of significant vascular damage were detected to account for this observation, although the tumor sections of the IL-2-and IL-2 plus melphalan-treated animals revealed scattered extravasation of erythrocytes compared with the untreated animals. Clear differences were seen in the localization of ED-1 cells, with an even distribution in the sham, IL-2 and melphalan treatments, whereas in the IL-2 plus melphalan-treated tumors clustered ED-1 cells were found. Additionally, increased levels of TNF mRNA were found in tumors treated with IL-2 and IL-2 plus melphalan. These observations indicate a potentially important role for macrophages in the IL-2-based perfusion. The results in our study indicate that the novel combination of IL-2 and melphalan in ILP has synergistic antitumor activity and may be an alternative for ILP with TNF and melphalan. (Cancer Res 2005; 65(10): 4300-8)

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Isolated limb perfusion with tumour necrosis factor-α and melphalan for unresectable bone sarcomas of the lower extremity

Cited by 33 publications

References 28 publications

Hyperthermic Isolated Limb Perfusion for Extremity Sarcomas

Hyperthermic Isolated Limb Perfusion for Extremity Sarcomas

Isolated limb perfusion with melphalan for femoral metastases of breast cancer: Case report

Synergistic Antitumor Response of Interleukin 2 with Melphalan in Isolated Limb Perfusion in Soft Tissue Sarcoma–Bearing Rats

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