Long-term Morbidity After Regional Isolated Perfusion With Melphalan for Melanoma of the Limbs

Vrouenraets, B. C.; Klaase, Joost M.; Kroon, Bin B. R.; Geel, Bert N. van; Eggermont, Alexander M.M.; Franklin, H. R.

doi:10.1001/archsurg.1995.01430010045009

Cited by 79 publications

(37 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4,5,23 The incidence of long-term neuropathy in melanoma patients treated with ILP with melphalan alone has been 20% after axillary ILP and 2% after iliac ILP in our institution, with other institutions reporting a wide range of long-term neuropathy in 1-48% of patients. 26 Finally, 31% of our patients who still were alive 1 year after ILP reported extremity malfunction to some extent, and 18% reported extremity malfunction after 2 years.…”

Section: Discussionmentioning

confidence: 61%

“…Severe regional toxicity can cause long-term impaired extremity function, and the risk of a shock-like syndrome is considerable if Ͼ 10% leakage of TNF␣ to the systemic circulation during ILP occurs. 10,11 Moreover, the risk of local recurrence after limb-sparing surgery is considerable, 8,12 and response and limb salvage rates after TNF␣-ILP are promising but vary and tend to get lower over time. 4 -7 In view of these observations, we studied the results of limb salvage surgery with TNF␣-ILP regarding toxicity, limb salvage rates, local recurrence rates, functional outcomes, and survival in patients with locally unresectable sarcoma of the extremities who were treated in our institution.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Isolated limb perfusion with tumor necrosis factor‐α and melphalan for patients with unresectable soft tissue sarcoma of the extremities

Noorda

Vrouenraets

Nieweg

et al. 2003

Cancer

Self Cite

View full text Add to dashboard Cite

BACKGROUNDSince 1992, isolated limb perfusion (ILP) with tumor necrosis factor‐α (TNFα) and melphalan has been used for the treatment of patients with unresectable soft tissue sarcomas of the extremities. The authors retrospectively studied the results of limb salvage surgery using TNFα‐ILP at their institution.METHODSFrom 1992 to 2001, 49 patients (mean age, 51 years; range, 14–85 years) underwent ILP for unresectable soft tissue sarcomas of the extremities. All patients received melphalan and TNFα (four patients also received interferon‐γ). The median follow‐up was 26 months (range, from 2 days to 103 months).RESULTSIn 1 patient (2%) who died 2 days after undergoing ILP, response and acute limb toxicity could not be assessed. One patient (2%) attained a clinical complete response (2%), 23 patients (47%) attained a clinical partial response, 17 patients (35%) demonstrated no change, and 7 patients (14%) had tumor progression. Thirty‐one patients (63%) underwent tumor resection. Histologic material also was available from eight amputations and three punctures/biopsies. Pathologic response was complete in 4 patients (8%), partial in 14 patients (29%), and no change was observed in 24 patients (49%). Final response, based on both clinical and pathologic assessment in which pathology was decisive, was complete in 4 patients (8%) and partial in 27 patients (55%), resulting in a final overall response rate of 63%. Local control with preservation of the limb was attained in 28 patients (57%). Four of 32 patients (13%) who had been rendered tumor free by ILP with or without undergoing resection and radiation therapy, developed a local recurrence. The 5‐year disease specific survival rate was 48% for the 49 patients. Acute limb toxicity after ILP was a mild Grade 1–2 reaction in 35 patients (71%) patients, a Grade 3 reaction in 12 patients (25%), and a Grade 4 reaction in 1 patient (2%). Three major ILP‐related complications were encountered, including arterial thrombosis in two patients and a fulminant Clostridial infection leading to death in one patient. There were no severe cardiovascular reactions after ILP.CONCLUSIONSIn patients with unresectable soft tissue sarcomas of the limbs who underwent ILP with TNFα and melphalan followed by resection of the tumor remnant when possible, a 63% overall tumor response rate and a 57% local control rate with limb preservation was achieved. Cancer 2003;98:1483–90. © 2003 American Cancer Society.DOI 10.1002/cncr.11648

show abstract

Section: Discussionmentioning

confidence: 61%

mentioning

confidence: 99%

Isolated limb perfusion with tumor necrosis factor‐α and melphalan for patients with unresectable soft tissue sarcoma of the extremities

Noorda

Vrouenraets

Nieweg

et al. 2003

Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…An argument against the use of high perfusion flow rates in ILP is the potential increased incidence of oedema, localized toxicity and leakage of melphalan to the systemic circulation with higher morbidity (Kroon, 1988;Omlor et al, 1990;Klaase et al, 1994b;Vrouenraets et al, 1995). However, flow rates higher than the physiological flow have been advocated to provide higher oxygenation (Fontijne et al, 1984(Fontijne et al, , 1985 or enable optimal tissue temperatures to be achieved more rapidly (Thompson et al, 1994a).…”

mentioning

confidence: 99%

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

“…This is critical, since the severity of acute regional toxicity is related to long-term morbidity and functionality of the limb. In patients experiencing grade III acute regional toxicity the rate of permanent long-term regional morbidity reaches 50% (muscle atrophy, tissue fibrosis, limb malfunction) (30,31). Moreover grade III reactions are not well accepted by patients and may prolong significantly hospital stay.…”

Section: Discussionmentioning

confidence: 99%

Hyperthermic isolated limb perfusion for recurrent melanomas and soft tissue sarcomas: Feasibility and reproducibility in a multi-institutional Hellenic collaborative study

Lasithiotakis

Economou²,

Gogas³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

Abstract. Hyperthermic isolated limb perfusion with TNF-· and melphalan (TM-HILP) is a complicated surgical procedure. Herein, we present the experience of the Hellenic collaborating centers with TM-HILP for inoperable in-transit melanoma and soft tissue sarcoma (STS) of the extremities to examine safety and feasibility of collaborating as a multiinstitutional group for future research studies. From 2001 to 2009, twenty patients (median age 63.5 years) underwent TM-HILP for locally advanced in-transit melanoma (n=14) or unresectable STS (n=6). All patients underwent a 90-min isolated limb perfusion with melphalan (10 mg/l limb volume) and TNF-· (1-2 mg) under mild hyperthermia (39-40˚C). No major intra-operative complications occurred and all patients completed the procedure successfully. One patient developed postoperative ischemic necrosis of the limb necessitating amputation. All melanoma patients showed a response to TM-HILP with 7 (62%) of them experiencing complete response. All STS patients attained complete response after excision of residual tumor. The median disease specific and limb-relapse-free survival was 15 and 12 months, respectively. TM-HILP can be safely applied even in low volume tertiary hospitals provided that technology to minimize intraoperative systemic leakage is available. Future prospective studies can be performed reproducibly by this multi-institutional collaborative group.

show abstract

Long-term Morbidity After Regional Isolated Perfusion With Melphalan for Melanoma of the Limbs

Abstract: Improvement of the perfusion technique should be pursued in an effort to reduce acute regional toxic reactions, and thereby long-term morbidity, without compromising the therapeutic effect.

Cited by 79 publications

References 18 publications

Isolated limb perfusion with tumor necrosis factor‐α and melphalan for patients with unresectable soft tissue sarcoma of the extremities

Isolated limb perfusion with tumor necrosis factor‐α and melphalan for patients with unresectable soft tissue sarcoma of the extremities

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

Hyperthermic isolated limb perfusion for recurrent melanomas and soft tissue sarcomas: Feasibility and reproducibility in a multi-institutional Hellenic collaborative study

Contact Info

Product

Resources

About