Hyperthermic regional perfusion with melphalan and a combination of melphalan and actinomycin D in the treatment of locally metastasized malignant melanomas of the extremities

Martijn, Hendrik; Oldhoff, J; Koops, Hs

doi:10.1002/jso.2930200103

Cited by 35 publications

(8 citation statements)

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“…Their work has prompted others to undertake similar studies. Rochlin and Smart [16], Krementz et al [10], Krementz and Campbell [11], Shingleton [21], Stehlin et al [3,22], McBride et al [7], Martijn et al [13][14][15], Schraffordt Koops et al [18--20], Johnsson et al [9], Illig and Aigner [8], Lejeune et al [12], Sugarbaker and McBride [23], Vaglini et al [25], Tonak et al [24], and Aigner et al [6] have achieved reasonable long-term survivals in selected patients with recurrent limb melanoma treated by surgical excision and adjuvant perfusion.…”

Section: Discussionmentioning

confidence: 99%

“…We have published 2 articles about patients treated by regional perfusion who had locally metastasized malignant melanomas of the extremities [14,15]. Only patients with local recurrence, satellitosis, or intransit metastases with or without lymph node metastases were analyzed in these studies.…”

Section: Perfusion In Patients With Local Recurrence Of Lntransit Met...mentioning

confidence: 99%

“…Only patients with local recurrence, satellitosis, or intransit metastases with or without lymph node metastases were analyzed in these studies. We evaluated survival and local recurrence after normothermic and hyperthermic perfusion [14] as well as the use of melphalan or a combination or melphalan and actinomycin-D as chemotherapeutic agents [15].…”

Section: Perfusion In Patients With Local Recurrence Of Lntransit Met...mentioning

confidence: 99%

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Isolated regional perfusion in malignant melanoma of the extremities

Koops

Oldhoff

et al. 1987

World j. surg.

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Isolated perfusion for regional chemotherapy is only practical for tumorsIdeated on the extremity, because this is the only site where adequate vascular occlusion can be achieved. Indications for perfusion in clinical stage I melanoma patients are determined by mierostaging of the tumor. At our institution, patients with Clark's levels III, IV, or V and a Breslow thickness of >--1.5 mm are eligible. Lower limb perfusions are started through an iliac perfusion. Two perfusions are performed for foot lesions, local recurrences, satellitosis, or intransit metastases.Flow rates for leg perfusion vary from 600 to 1,000 ml/min. During the past few years, higher flows (up to about 1,200 ml/min) have been utilized. Less toxicity developed with better tissue perfusion, and the dosage of cytostatics could be increased. The dosage of cytostatic drugs is calculatedby limb volume, as determined by immersion in water. In our opinion, hyperthermia yields superior results for eases of local recurrence or intransit metastases. It is not known if a combination of cytostatic drugs might improve results compared to a single drug.The principle of regional perfusion using cytostatic drugs resuited from a study by Klopp et al. [l] in 1950, who found that pain was alleviated and tumor size reduced when small doses of nitrogen mustard (chlormethine) were injected into the regional arterial blood flow. The best results were obtained when venous return from the area involved was blocked. In 1959, Creech et al. [2] combined this procedure with extracorporeal circulation, using a pump oxygenator, which made it possible to administer large doses of nitrogen mustard continuously.In 1960, Stehlin et al.[3] reported 116 regional perfusions performed at the M.D. Anderson Hospital in Houston, Texas, U.S.A. The majority of patients had tumors of the extremities; the remainder had tumors of the pelvic region and the head and neck area. Luck discovered that melphalan (L-phenylalanine mustard) was the most active agent to inhibit the growth of malignant melanoma in mice; this has since been the agent of choice in perfusions [4]. In 1967, Cavaliere et al. [5] laid the foundation for perfusions under hyperthermia when he described the susceptibility of cancer cells to high temperatures.Favorable results with regional limb perfusion of the extremities have been reported by numerous investigators [6--25]. Perfusion of melanomas located in other parts of the body is not possible, however, because leakage to the systemic circulation

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Section: Discussionmentioning

confidence: 99%

Section: Perfusion In Patients With Local Recurrence Of Lntransit Met...mentioning

confidence: 99%

Section: Perfusion In Patients With Local Recurrence Of Lntransit Met...mentioning

confidence: 99%

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Isolated regional perfusion in malignant melanoma of the extremities

Koops

Oldhoff

et al. 1987

World j. surg.

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“…Actinomycin D is an anticancer antibiotic that has been used in patients with osteogenic sarcoma in combination with bleomycin and cyclophosphamide but this treatment is associated with severe nausea and anorexia (69). Martijn et al showed that melphalan-based ILP with actinomycin D in patients with IT-mets offer no improved response rates compared to melphalan alone (70). However, actinomycin D increase the TNF sensitivity of tumor cells in vitro (71) and local administration of TNF in combination with actinomycin D in mice delays the growth of several tumors (72,73).…”

Section: The Isolated Limb Perfusionmentioning

confidence: 99%

TNF and manipulation of the tumor cell - stromal interface: "ways to make chemotherapy effectiv"

Seynhaeve¹

2008

Front Biosci

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Growth of solid tumors depends largely on the development of a functional vasculature, which has been the focus in anti-tumor therapy since Folkman in 1971 proposed that prohibiting the formation of new vessels could inhibit tumor growth. The recognition of the tumor vascular bed as an important target led to the development of 3 vascular-targeted strategies. I) The anti-angiogenesis strategy that prevents the formation of new blood vessels and normalizes the remaining vessels. II) Applying vasculo-destructive agents to induce apoptosis in the endothelium of the tumor-associated vasculature that results in vascular collapse and tumor necrosis. III) Promoting further abnormalization of the already abnormal features of the tumor-associated vasculature with vaso-active agents to enhance vessel permeability. Tumor necrosis factor alpha (TNF) is a very promising vaso-active agent because of its anti-tumor effects but its severe systemic toxicity is a major drawback. Therefore a new setting, in which the optimal therapeutic benefit of TNF could be exploited, needed to be found. Through an isolated perfusion high dose of TNF can be administered in the blood circulation of the tumor-bearing extremity or organ. Alternatively, systemically low doses can be safely administered for several times. Importantly, TNF has no anti-tumor effect by itself and the combination with a conventional chemotherapeutic drug that targets the tumor cell is a prerequisite for a good tumor response. In this dual approach, TNF enhances intratumoral accumulation of the chemotherapeutic drug resulting in an impressive tumor response.

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“…A number of agents have been administered via ILP including cisplatin [39,[56][57][58][59][60], cisplatin and etoposide [61], melphalan and actinomycin D [62], DTIC [63,64], or IL-2 and LAK cells [64,65]. Despite the substantial clinical experience with other agents it does not appear that any have superior efficacy or less toxicity than melphalan alone [66].…”

Section: Isolated Limb Perfusion With Other Agentsmentioning

confidence: 99%

Isolated limb perfusion for malignant melanoma

Alexander¹,

Fraker²,

Bartlett³

1996

Semin. Surg. Oncol.

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The technique of isolated limb perfusion (ILP) for the treatment of extremity melanoma has been used in the United States for almost 40 years. The treatment is based upon the ability to isolate the circulation of the afflicted extremity from the systemic circulation, thereby allowing dose‐intensive delivery of anti‐cancer agents to the limb while eliminating systemic exposure and toxicity. A number of agents have been used in ILP, however, the bulk of clinical experience has been with the alkylating agent melphalan, typically used under conditions of mild hyperthermia. Despite considerable clinical experience, there has been a lack of agreement about the role of ILP in the prophylaxis against or the treatment of recurrent extremity melanoma. Recently there has been renewed interest in the use of ILP based upon the very promising results using a combination of tumor necrosis factor, melphalan, and interferon‐gamma which have produced complete response (CR) rates of almost 90%. The utility of this regimen in extremity melanoma is actively being evaluated by clinical trials in the United States and Europe. © 1996 Wiley‐Liss, Inc.

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Hyperthermic regional perfusion with melphalan and a combination of melphalan and actinomycin D in the treatment of locally metastasized malignant melanomas of the extremities

Cited by 35 publications

References 15 publications

Isolated regional perfusion in malignant melanoma of the extremities

Isolated regional perfusion in malignant melanoma of the extremities

TNF and manipulation of the tumor cell - stromal interface: "ways to make chemotherapy effectiv"

Isolated limb perfusion for malignant melanoma

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