Management of recurrent melanoma of the extremity

Shingleton, William W.; Seigler, Hilliard F.; Stocks, Lewis H.; Downs, Robert W.

doi:10.1002/1097-0142(197503)35:3<574::aid-cncr2820350303>3.0.co;2-5

Cited by 17 publications

(2 citation statements)

References 12 publications

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“…In advanced, regionally confined disease, there does not seem to be any disagreement about the benefits obtained from perfusion. Results reported by others similar to those reported in this paper are listed in Table 14 [21,26,[28][29][30][35][36][37]. Perhaps one of the most important achievements of regional chemotherapy and other adjunctive regional modalities is that amputation, a procedure that was widely used in the treatment of this disease 20 years ago, is now seldom, if ever, needed to control limb melanoma.…”

Section: Number Ofsupporting

confidence: 76%

The use of regional chemotherapy in the management of malignant melanoma

et al. 1979

World j. surg.

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From 1957 through 1977, a total of 714 patients with malignant melanoma were treated by chemotherapy administered by isolated regional perfusion of the limbs, and 56 patients were treated by intra-arterial infusion.Excisionai surgery and adjunctive perfusion in 286 patients with stage I disease resulted in cumulative survival rates of 87% at 5 years and 75% at 10 and 15 years. With recurrent or metastatic regional disease treated by perfusion alone or in combination with surgical excision, the survival rates were 36%, 34%, and 31% at 5, 10, and 15 years, respectively. Even in the least favorable group, those with nodal and soft tissue involvement, the survival rates were 27% at 5 years and 22.5% at 10 and 15 years. Analysis of 121 patients with stage I melanoma according to level of dermal invasion showed recurrence in 2 of 42 (4%) patients with level III lesions, 11 of 75 (15%) with level IV tumors, and 2 of 4 (50%) with level V lesions. Recurrence rates by pathologic type were 2 of 49 (4%) patients with superficial spreading melanoma, 6 of 30 (20%) with nodular melanoma, and 5 of 14 (36%) with acral lentiginous melanoma, the latter including subungual, plantar, or palmar lesions.Chemotherapy by intra-arterial infusion is a technique useful in treating regional disease not amenable to isolationperfusion. Of 36 patients having measurable lesions, there were 4 complete responses. Objective responses occurred in 50-80% of patients treated, depending on the agent used.As an adjunct to surgical treatment, Chemotherapy by isolation-perfusion offers improved survival rates without prolonged treatment or the risks associated with systemic chemotherapy. As primary therapy for advanced regional disease, chemotherapy by perfusion produces survival rates superior to those obtained by surgery alone or systemic chemotherapy.

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Section: Number Ofsupporting

confidence: 76%

The use of regional chemotherapy in the management of malignant melanoma

et al. 1979

World j. surg.

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“…The dose of melphalan used in isolated limb varies from centre to centre. In most series the dose is calculated on the basis of body weight, and the most commonly recommended dose for an iliac perfusion is 1-1.5 mg per kilogram of body weight (Krementz, 1986;Shingleton et al, 1975;Bulman & Jamieson, 1980;Storm & Morton, 1985;Ghussen et al, 1984;Schraffordt Koops et al, 1981). In a few studies it has been suggested that doses as high as 2 mg per kilogram of body weight can be given (Rosin & Westbury, 1980;Fontaine & Jamieson, 1974).…”

Section: Pharmacokinetics Of Bolus Administrationmentioning

confidence: 99%

The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma

Scott

Kerr²,

Blackie³

et al. 1992

Br J Cancer

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Summary We describe melphalan pharmacokinetics in 26 patients treated by isolated limb perfusion (ILP). Group A (n = 11) were treated with a bolus of melphalan (1.5 mg kg-'), and in a phase I study the dose was increased to 1.75 mg kg-'. The higher dose was given as a bolus to Group B (n = 9), and by divided dose to Group C (n = 6).Using high performance liquid chromatography (HPLC) the concentrations of melphalan in the arterial and venous perfusate (during ILP) and in the systemic circulation (during and after ILP) were measured. Areas under the concentration time curves for perfusate (AUCa, AUCV) and systemic (AUCS) data were calculated. In all three groups the peak concentrations of melphalan were much higher in the perfusate than in the systemic circulation. The pharmacokinetic advantages of ILP can be quantified by the ratio of AUCa/AUCS, median value 37.8 (2.1-131).AUCG and AUC, were both significantly greater in Group B than in Group A (P values <0.01, Mann-Whitney). In Groups B and C acceptable 'toxic' reactions occurred but were not simply related to melphalan levels.Our phase I study has allowed us to increase the dose of melphalan to 1.75 mg kg-', but we found no pharmacokinetic advantage from divided dose administration.The rationale for isolated limb perfusion (ILP) in the management of cancer depends on the generation of high levels of effective anticancer agent confined to the tumourbearing limb, thereby avoiding unacceptable systemic toxicity.It is clearly important to establish whether the complex and expensive technique of ILP genuinely achieves its major aim i.e. maximum levels of melphalan in the tumour-bearing limb and minimum systemic exposure.ILP is effective in the management of locally advanced malignant melanoma, and may be an effective adjuvant to surgery for thick, high risk primary lesions. Having reviewed our early experience of patients treated by ILP, it was confirmed that, because of the absence of melphalan-induced toxicity, there was scope for a phase I (dose escalating) clinical study.The study of pharmacokinetics is concerned with the absorption, distribution, biotransformation and excretion of drugs (Goodman et al., 1985). For a given dose these factors govern the concentration of drug at the site of action and they determine how the concentration varies with time.We have studied melphalan pharmacokinetics in the context of a phase I study of ILP.The aims of our studies were:(1) to measure melphalan concentrations in perfusate during ILP, and compare these with the levels in the systemic circulation during and after perfusion, (2) to study the pharmacokinetics of melphalan in ILP, as the dose was increased in a phase I study, (3) to compare the pharmacokinetics of bolus dose with divided dose administration.Patients, materials and methods Patient groupsOnly patients having external iliac perfusion for malignant melanoma were included in the study. The starting dose of melphalan was 1.5 mg kg' body weight, which is the maximum dose recommended in the protocols on which our t...

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