Local and systemic toxicity in ??borderline true?? hyperthermic isolated perfusion for lower limb melanoma

Pace, M; Galli, Alessandro; Bellacci, A.

doi:10.1097/00008390-199510000-00011

Cited by 8 publications

(7 citation statements)

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“…In the ILP setting, however, real hyperthermia with temperatures higher than 40.58C leads to unacceptable toxicity, including severe tissue necrosis, which often requires amputation. 19,20 Furthermore, data from clinical studies could not demonstrate a correlation between ILP-induced tumor hyperthermia and treatment response. 21 Therefore, mild hyperthermia with a maximal tumor temperature of 39.58C is generated in the limb circuit before the administration of rhTNFa and melphalan.…”

Section: Mode Of Action Of Tnf-ilpmentioning

confidence: 99%

“…This so‐called thermal chemosensitization is most likely based on increased drug uptake and chemical activity. In the ILP setting, however, real hyperthermia with temperatures higher than 40.5°C leads to unacceptable toxicity, including severe tissue necrosis, which often requires amputation . Furthermore, data from clinical studies could not demonstrate a correlation between ILP‐induced tumor hyperthermia and treatment response .…”

Section: Mode Of Action Of Tnf‐ilpmentioning

confidence: 99%

“…Just as any therapeutic intervention, ILP has evolved over time: The limb circuit is heated until a tumor temperature of 38 to 39.5°C is reached because higher temperatures lead to unacceptable local toxicity . Notably, the tumor and muscle temperature should be measured because often soft tissue sarcomas do exhibit higher temperatures than normal tissue; this relation is reversed during the heating process .…”

Section: Current Standards In Tnf‐ilpmentioning

confidence: 99%

“…The limb circuit is heated until a tumor temperature of 38 to 39.58C is reached because higher temperatures lead to unacceptable local toxicity. 19,20 Notably, the tumor and muscle temperature should be measured because often soft tissue sarcomas do exhibit higher temperatures than normal tissue; this relation is reversed during the heating process. 21 Both aspects may be explained by the dysfunctional tumor vasculature, which is one of the targets of rhTNFa.…”

Section: Current Standards In Tnf-ilpmentioning

confidence: 99%

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Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Jakob

Hohenberger

2016

Cancer

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Isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan (TNF-ILP) is a highly effective regional treatment for locally advanced soft tissue sarcoma. This review critically discusses the indication for TNF-ILP. AbstractManagement of locally advanced extremity soft tissue sarcoma of the limbs is challenging particularly in recurrent tumors and those adjacent to neurovascular bundles and joints. Typically the tumors are large, below the fascia and of high grade (T2b, stage III according to AJCC) and thus require multimodal therapy. Treatment options must be tailored to patient and tumor characteristics.Isolated limb perfusion with recombinant human tumor necrosis factor α (TNF-ILP) adds a therapeutic option to radiation therapy and systemic chemotherapy. Although the procedure is somewhat sophisticated to learn, it is a safe method working for now almost two decades in more than 50 centers worldwide. TNF-ILP yields a high rate of pathologic complete or near-complete tumor remission. Combined with post-ILP surgical resection of the tumor remnant the limb salvage rate is close to 90%. Often adjuvant radiation therapy can be spared without compromising longterm local tumor control rates. Nevertheless, TNF-ILP has never been compared to other treatment regimen in a randomized trial. This review summarizes the mode of action and the standard application of TNF-ILP and focuses on a critical discussion on the role of TNF-ILP in multimodal treatment of locally advanced primary and recurrent extremity sarcoma.

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Section: Mode Of Action Of Tnf-ilpmentioning

confidence: 99%

Section: Mode Of Action Of Tnf‐ilpmentioning

confidence: 99%

Section: Current Standards In Tnf‐ilpmentioning

confidence: 99%

Section: Current Standards In Tnf-ilpmentioning

confidence: 99%

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Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Jakob

Hohenberger

2016

Cancer

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“…The European multi center trial studies by Overgaard et al [34] suggested that adjuvant hyperthermia signifi cantly improved local tumor control when applied in association with radiation in the treatment of malignant melanoma. Clinical data of a hyperthermal (41.5°C) isolated per fusion of the lower limb for melanoma treat ment in association with cytostatic drugs (L-PAM) reported in 10 consecutive patients in dicated that high-temperature treatments with simultaneous administration of drugs are feasible and have an acceptable toxicity [35]. Perfusions using high-dose hyperther mia and melphalan sequentially have been tried for the management of recurrent mela noma of the limbs [36], The effect of mild hyperthermia (41.5 ° C) on the cytotoxic activ ity of a 1-hour melphalan exposure in human melanoma cell lines showed that hyperther mia can stabilize the G2 accumulation in duced by melphalan in human melanoma cell and may contribute to the enhancement of melphalan cytotoxicity by hyperthermia [37], Di-Fillipo et al [38] used local hyperthermia and systemic chemotherapy for the treatment of recurrent or metastatic melanoma.…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia Potentiates Antitumor Effect of Thermosensitive-Liposome- Encapsulated Melphalan and Radiation in Murine Melanoma

Chelvi

Ralhan²

1997

Tumor Biol

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Malignant melanoma are chemoresistant tumors with poor prognosis. The aim of this study was to determine whether multimodality therapy of murine melanoma involving a combination of radiation with thermosen-sitive-liposome-encapsulated melphalan and local hyperthermia would result in enhancement of therapeutic efficacy for a more effective management of melanoma. Melphalan was entrapped in thermosensitive liposomes prepared from natural lipids: egg phosphatidyl choline, cholesterol and ethanol to show phase transition at 42 ± 0.5° C and used in combination with localized heating of B16F10 murine melanoma transplanted into the legs of C57B1/6 mice for selective drug targeting at the tumors and/or radiation for treatment of melanoma. Murine melanoma transplanted into C57B1/6 mice were subjected to bimodality treatments involving a combination of radiation, hyperthermia or melphalan. Partial tumor regression was observed in mice receiving a combination of hyperthermia and radiation (median tumor volume 427.3 mm³) or a combination of free melphalan and radiation (512.1 mm³) as compared to untreated controls (630.9 mm³). Each group consisted of 18 animals, and the results are expressed as median tumor volume ± SD. Animals receiving multimodality therapy comprising irradiation followed by injection of thermosensitive liposomal melphalan and hyperthermic treatment of the tumor-bearing leg at 42 ± 0.5°C for 1 h showed marked tumor regression in comparison with untreated controls or animals treated with a combination of radiation and hyperthermia or radiation and free-drug melphalan. Animals receiving thermoradiochemotherapy also showed prolonged survival; 70% of animals survived for more than 3 months. The study shows greater tumor cell killing, tumor growth delay and prolonged survival produced by a combination of radiation, thermosensitive-liposome-entrap-ped melphalan and hyperthermia compared with animals receiving single-modality or bimodality treatments. It is concluded that this multimodality approach will be potentially useful for more effective management of melanoma.

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Toxicity and morbidity of isolated limb perfusion

Vrouenraets

Klaase

Nieweg

et al. 1998

Semin. Surg. Oncol.

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Local and systemic toxicity in ??borderline true?? hyperthermic isolated perfusion for lower limb melanoma

Cited by 8 publications

References 0 publications

Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Hyperthermia Potentiates Antitumor Effect of Thermosensitive-Liposome- Encapsulated Melphalan and Radiation in Murine Melanoma

Toxicity and morbidity of isolated limb perfusion

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