Isolated limb perfusion for melanoma: Effectiveness and toxicity of cisplatin compared with that of melphalan and other drugs

Thompson, John F.; Gianoutsos, Mark P.

doi:10.1007/bf02071525

Cited by 121 publications

(51 citation statements)

References 33 publications

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“…Melphalan has been the standard drug for this regional treatment because of low regional toxicity (Thompson and Gianoutsos, 1992). ILPs with melphalan or other cytostatic drugs has also been used in the treatment of patients with extremity soft tissue sarcomas, although with little success (Kremetz et al, 1977;Klaase et al, 1989).…”

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confidence: 99%

Prerequisites for effective isolated limb perfusion using tumour necrosis factor alpha and melphalan in rats

et al. 1999

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MelphalanMelphalan (Alkeran, 50 mg per vial, Wellcome, Beckenham, UK) was diluted in 10 ml solvent. Further dilutions were made in 0.9% sodium chloride to give a concentration of 1 µg µl -1 . A volume of 40 µl (= 40 µg) was added to the perfusion circuit.Prerequisites for effective isolated limb perfusion using tumour necrosis factor alpha and melphalan in rats Summary An isolated limb perfusion (ILP) model using soft tissue sarcoma-bearing rats was used to study prerequisites for an effective ILP, such as oxygenation of the perfusate, temperature of the limb, duration of the perfusion and concentration of tumour necrosis factor (TNF). Combination of 50 µg TNF and 40 µg melphalan demonstrated synergistic activity leading to a partial and complete response rate of 71%. In comparison to oxygenated ILP, hypoxia was shown to enhance anti-tumour activity of melphalan alone and TNF alone but not of their combined use. Shorter perfusion times decreased anti-tumour responses. At a temperature of 24-26°C, anti-tumour effects were lost, whereas temperatures of 38-39°C or 42-43°C resulted in higher response rates. However, at 42-43°C, local toxicity impaired limb function dramatically. Synergy between TNF and melphalan was lost at a dose of TNF below 10 µg in 5 ml perfusate. We conclude that the combination of TNF and melphalan has strong synergistic anti-tumour effects in our model, just as in the clinical setting. Hypoxia enhanced activity of melphalan and TNF alone but not the efficacy of their combined use. For an optimal ILP, minimal perfusion time of 30 min and minimal temperature of 38°C was mandatory. Moreover, the dose of TNF could be lowered to 10 µg per 5 ml perfusate, which might allow the use of TNF in less leakage-free or less inert perfusion settings.

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confidence: 99%

Prerequisites for effective isolated limb perfusion using tumour necrosis factor alpha and melphalan in rats

et al. 1999

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“…Melphalan is an alkylating agent currently used systemically to treat multiple myeloma and ovarian cancer. Melphalan has also been used intraarterially with good results for the treatment of limb melanoma (using isolated limb perfusion), 5,13,21 for the treatment of colorectal metastatic disease to the liver (chemoembolization), and it has also shown effectiveness against lung metastases 8,10 and soft-tissue sarcoma. 5 Because melanoma and colorectal carcinoma are relatively radioresistant tumors, we expected that these histological types would be common in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Spinal intraarterial chemotherapy: interim results of a Phase I clinical trial

Patsalides

Yamada

Bilsky

et al. 2016

SPI

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OBJECT Despite advances in therapies using radiation oncology and spinal oncological surgery, there is a subgroup of patients with spinal metastases who suffer from progressive or recurrent epidural disease and remain at risk for neurological compromise. In this paper the authors describe their initial experience with a novel therapeutic approach that consists of intraarterial (IA) infusion of chemotherapy to treat progressive spinal metastatic disease. METHODS The main inclusion criterion was the presence of progressive, metastatic epidural disease to the spine causing spinal canal compromise in patients who were not candidates for the standard treatments of radiation therapy and/or surgery. All tumor histological types were eligible for this trial. Using the transfemoral arterial approach and standard neurointerventional techniques, all patients were treated with IA infusion of melphalan in the arteries supplying the epidural tumor. The protocol allowed for up to 3 procedures repeated at 3- to 6-week intervals. Outcome measures included physiological measures: 1) periprocedural complications according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events; and 2) MRI to assess for tumor response. RESULTS Nine patients with progressive spinal metastatic disease and cord compression were enrolled in a Phase I clinical trial of selective IA chemotherapy. All patients had metastatic disease from solid organs and were not candidates for further radiation therapy or surgery. A total of 19 spinal intraarterial chemotherapy (SIAC) procedures were performed, and the follow-up period ranged from 1 to 7 months (median 3 months). There was 1 serious adverse event (febrile neutropenia). Local tumor control was seen in 8 of 9 patients, whereas tumor progression at the treated level was seen in 1 patient. CONCLUSIONS These preliminary results support the hypothesis that SIAC is feasible and safe.

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“…and probably patient selection. In terms of objective complete response rate, results from 7% to 81% -the majority being in the range of 40-50% -were reported using melphalan which has been regarded as the standard drug for HILP [11][12][13]. Achieving a complete response is of great importance, above all in cases of nonresectable intransit metastases, because local tumor relapse and progression of disease is less probable in comparison to only a partial response.…”

Section: Discussionmentioning

confidence: 99%

Hyperthermic Isolated Limb Perfusion – 23 Years’ Experience and Improvement of Results by Modification of Technique

Meyer¹,

Göhl²,

Haas³

et al. 1998

Oncol Res Treat

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Isolated limb perfusion for melanoma: Effectiveness and toxicity of cisplatin compared with that of melphalan and other drugs

Cited by 121 publications

References 33 publications

Prerequisites for effective isolated limb perfusion using tumour necrosis factor alpha and melphalan in rats

Prerequisites for effective isolated limb perfusion using tumour necrosis factor alpha and melphalan in rats

Spinal intraarterial chemotherapy: interim results of a Phase I clinical trial

Hyperthermic Isolated Limb Perfusion – 23 Years’ Experience and Improvement of Results by Modification of Technique

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