Isolated lung perfusion with melphalan: Pharmacokinetics and toxicity in a pig model

Elst, A. van der; Oosterling, Steven J.; Paul, Marinus A.; Vonk, AB; Sparidans, Rolf W.; Sijp, Joost R.M. van der

doi:10.1002/jso.20498

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…In another study, pigs submitted to IVLP with and without chemotherapy demonstrated higher histologic injury scores and impairment of functional parameters compared with a sham group. 16 Histologic signs of hemorrhagic edema were found in both the control and melphalan-treated groups, 17 raising the question of the potential role that the perfusion circuit may have in causing injury. More recently, Pages and colleagues 18 performed IVLP for 30 minutes in 50-kg pigs, with a perfusion flow that ranged from 500 to 600 mL/min (adjusted to a PA pressure of around 25 mm Hg) and found that the control group had even greater histologic injury compared with lungs perfused with gemcitabine.…”

Section: Discussionmentioning

confidence: 99%

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Santos

Machuca

Hwang

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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Section: Discussionmentioning

confidence: 99%

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Santos

Machuca

Hwang

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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“…This is the first and only reported study showing the additional effects of two chemotherapeutic agents in the setting of ILuP and it is a promising tool for future phase I clinical studies. The pharmacokinetic properties of ILuP with melphalan have also been investigated in a pig model, demonstrating its feasibility, safety and the absence of any systemic toxicity (159).…”

Section: Melphalanmentioning

confidence: 99%

Lung Metastatic Disease: Surgical Resection and Locoregional Chemotherapy

Hengst¹,

Hendriks²,

Schil³

2012

Toraks Cer Bult

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Currently, surgical resection remains the gold standard for resectable lung metastases. Prognostic factors are histology, complete resection, number of metastases and disease-free interval. However, there is a high rate of recurrent disease in the thorax, even if systemic chemotherapy is applied. Because the latter is limited in dose due to systemic toxicity, new treatment options are being developed to selectively deliver high-dose chemotherapy into the lung, reducing systemic toxicity. Isolated lung perfusion (ILuP), similar to isolated limb perfusion, is an experimental surgical technique to deliver highdose chemotherapy into the lung without systemic exposure. Biological response modifiers like tumour necrosis factor can also be administered. ILuP results in significantly higher concentration of chemotherapy in the target organ compared to systemic chemotherapy, together with a survival benefit in experimental models of pulmonary metastases. Several phase I studies have shown that ILuP is technically feasible with low morbidity and low impact on the patient's pulmonary function. However, the utility of this technique is limited because it is an invasive technique. Other techniques to selectively deliver high-dose locoregional chemotherapy are embolic trapping (chemo-embolization), selective pulmonary artery perfusion (SPAP) without control of the venous effluent and the minimally invasive lung suffusion technique. This review will discuss surgical resection of lung metastases and address several techniques developed to deliver high doses of chemotherapy into the lung, as well as the current progress in experimental and clinical studies.

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“…Pharmacokinetics of melphalan were further investigated in a pig model by van der Elst et al demonstrating a safe pharmacokinetic profile without systemic toxicity [45].…”

Section: Melphalanmentioning

confidence: 99%

Isolated lung perfusion and related techniques for the treatment of pulmonary metastases☆

Schil

Hendriks

Putte

et al. 2008

European Journal of Cardio-Thoracic Surgery

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Surgical resection is a widely accepted treatment for pulmonary metastases on the condition that a complete resection can be obtained. However, many patients will develop recurrent disease in the thorax despite the use of systemic chemotherapy, dosage of which is limited because of systemic toxicity. Similar to the basic principles of isolated limb and liver perfusion, isolated lung perfusion is an attractive and promising surgical technique for the delivery of high-dose chemotherapy with minimal systemic toxicity. The use of biological response modifiers, like tumour necrosis factor, is also feasible. Other related methods of delivering high-dose locoregional chemotherapy include embolic trapping (chemo-embolisation) and pulmonary artery infusion without control of the venous effluent. Isolated lung perfusion has proven to be highly effective in experimental models of pulmonary metastases with a clear survival advantage. Lung levels of cytostatic drugs are significantly higher after isolated lung perfusion compared to intravenous therapy without systemic exposure. Phase I human studies have shown that isolated lung perfusion is technically feasible with low morbidity and without compromising the patient's pulmonary function. Further clinical studies are necessary to determine its definitive effect on local recurrence, long-term toxicity, pulmonary function and survival.

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Isolated lung perfusion with melphalan: Pharmacokinetics and toxicity in a pig model

Cited by 6 publications

References 23 publications

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Lung Metastatic Disease: Surgical Resection and Locoregional Chemotherapy

Isolated lung perfusion and related techniques for the treatment of pulmonary metastases☆

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