Melphalan concentration and distribution in the tissues of tumour-bearing limbs treated by isolated limb perfusion

Scott, R. N.; Blackie, Robert; Kerr, D. J.; Hughes, Jeffery S.; Burnside, Girvan; Rm, MacKie; Byrne, Dominique; McKay, A. J.

doi:10.1016/0959-8049(92)90009-q

Cited by 20 publications

(9 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Perfusate compositions and tissue concentrations of melphalan Scott et al (1990) found a similar mean melphalan concentration in tumour and healthy skin during LLP using Ringer's lactate solution with packed red cells. Klaase et al (1994a) reported preferential uptake of melphalan into tumour tissue during ILP using electrolyte solution with whole blood.…”

Section: Discussionmentioning

confidence: 62%

“…Of more direct clinical relevance is the targeting of melphalan within melanoma nodules relative to normal tissues. Currently, there are limited data on melphalan distribution in melanoma nodules and within the tissues of the tumourbearing limb during ILP (Scott et al, 1990;Klaase et al, 1994a).…”

mentioning

confidence: 99%

“…Although ILP has been in use for many years to treat recurrent melanoma restricted to the limbs (Krementz et al, 1987;Scott et al, 1992a;Thompson et al, 1994a) and sarcomas of the extremities (Englund et al, 1971;Lejeune et al, 1988;Kettelhack et al, 1990), the optimal perfusion conditions have been ill defined. Currently, different perfusate compositions are used in the different centres undertaking ILP: Ringer's lactate solution with packed red cells or whole blood (Krementz et al, 1987;Scott et al, 1992a); electrolyte solution with whole blood (Kroon, 1988;Klasse et al, 1994a); or Hartmann's solution (high chloride content) with packed red cells (Thompson et al, 1994a) and the inclusion of dextran to maintain oncotic pressure (Egerton, 1982).…”

mentioning

confidence: 99%

“…Currently, different perfusate compositions are used in the different centres undertaking ILP: Ringer's lactate solution with packed red cells or whole blood (Krementz et al, 1987;Scott et al, 1992a); electrolyte solution with whole blood (Kroon, 1988;Klasse et al, 1994a); or Hartmann's solution (high chloride content) with packed red cells (Thompson et al, 1994a) and the inclusion of dextran to maintain oncotic pressure (Egerton, 1982). We are not aware of any study that has compared the effects of variations in perfusate composition on melphalan distribution within tumour nodules and normal tissues during ILP.…”

mentioning

confidence: 99%

See 3 more Smart Citations

The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft

Smithers²,

Parsons³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary An isolated rat hindlimb perfusion model carrying xenografts of the human melanoma cell line MM96 was used to study the effects of perfusion conditions on melphalan distribution. Krebs-Henseleit buffer and Hartmann's solution containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 were used as perfusates. Melphalan concentrations in perfusate, tumour nodules and normal tissues were measured using high-performance liquid chromatography (HPLC). Increasing the perfusion flow rates (from 4 to 8 ml min-') resulted in higher tissue blood flow (determined with 5'Cr-labelled microspheres) and melphalan uptake by tumour and normal tissues. The distribution of melphalan within tumour nodules and normal tissues was similar for both Krebs-Henseleit buffer and Hartmann's solution; however, tissue concentrations of melphalan were significantly higher for a perfusate containing 2.8% dextran 40 than for one containing 4.7% BSA. The melphalan concentration in the tumour was one-third of that found in the skin if the perfusate contained 4.7% BSA. In conclusion, this study has shown that a high perfusion flow enhances the delivery of melphalan into implanted tumour nodules and normal tissues, and a perfusate with low melphalan binding (no albumin) is preferred for maximum uptake of drug by the tumour.

show abstract

Section: Discussionmentioning

confidence: 62%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft

Smithers²,

Parsons³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…77 Besides antiproliferative and cytotoxic activity, 78 rhTNF-␣ induces morphologic changes, increased expression of cellsurface receptors and adhesion molecules, and procoagulant activity, 79,80 but it has also been reported to cause increased drug concentrations. 39, 81,82 In conclusion, this is the first study to provide data about expression modulation of MDR genes determined sequentially before, during, and after hyperthermic ILP by using rhTNF-␣ and cytostatic drugs. Although induction of MVP was found in the majority of the tumors, there was no correlation with histologic or clinical response to therapy.…”

Section: Discussionmentioning

confidence: 93%

Expression of Multidrug Resistance GenesMVP,MDR1, andMRP1Determined Sequentially Before, During, and After Hyperthermic Isolated Limb Perfusion of Soft Tissue Sarcoma and Melanoma Patients

Stein

Jürchott

Schläfke

et al. 2002

JCO

View full text Add to dashboard Cite

show abstract

Isolated limb perfusion for malignant melanoma

Alexander¹,

Fraker²,

Bartlett³

1996

Semin. Surg. Oncol.

View full text Add to dashboard Cite

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.

show abstract

Melphalan concentration and distribution in the tissues of tumour-bearing limbs treated by isolated limb perfusion

Cited by 20 publications

References 4 publications

The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft

The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft

Expression of Multidrug Resistance GenesMVP,MDR1, andMRP1Determined Sequentially Before, During, and After Hyperthermic Isolated Limb Perfusion of Soft Tissue Sarcoma and Melanoma Patients

Isolated limb perfusion for malignant melanoma

Contact Info

Product

Resources

About