title: Hypoxic antiblastic stop-flow limb perfusion: clinical outcome and pharmacokinetic findings of a novel treatment for in transit melanoma metastases.
abstract: Hypoxic antiblastic stop-flow perfusion (SFP) has recently been proposed as a therapeutic option for patients with locally advanced tumors. We report on the clinical and pharmacological results of our prospective study of limb SFP for the treatment of in transit melanoma metastases. Twenty-three patients with limb-sited melanoma metastases were treated with melphalan (10 mg/l) based pelvic (n=11, group A) or femoral (n=12, group B) SFP under hypoxic conditions. Systemic and locoregional toxicity, tumor response rate, and local progression-free survival were analyzed. Melphalan concentrations were measured in the perfusate and systemic circulation during SFP, and after 30-min hemofiltration. Perfusate-to-plasma leakage was assessed using a scintigraphic method. No postoperative deaths occurred. Mild locoregional toxicity was observed in 5 patients (18%), and systemic toxicity was mild to severe in 8 patients (30%), the incidence being higher in group A. Tumor response rate (complete + partial response) and time to local disease progression were significantly different in group A and B (9% vs 58% and 7 vs 13 months, respectively). The pharmacokinetic study showed that pelvic SFP was associated with a higher leakage rate and a lower area under the curve ratio than femoral SFP (44% vs 31% and 5.6 vs 9.8, respectively). Limb SFP is a feasible and relatively simple procedure. Toxicity and tumor response rates strictly depend upon drug leakage control. Further efforts should be made to exploit the potential anti-tumor activity of this novel locoregional drug delivery system.
authors.affiliation: Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Pilati
authors.forename: Simone
authors.initials: S
authors.lastname: Mocellin
authors.forename: Diego
authors.initials: D
authors.lastname: Miotto
authors.forename: Claudio
authors.initials: C
authors.lastname: Fittà
authors.forename: Dario
authors.initials: D
authors.lastname: Casara
authors.forename: Carlo
authors.initials: C
authors.lastname: Ori
authors.forename: Romano
authors.initials: R
authors.lastname: Scalerta
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Mario
authors.initials: M
authors.lastname: Lise
authors.forename: Carlo Riccardo
authors.initials: CR
authors.lastname: Rossi
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D010478:Chemotherapy, Cancer, Regional Perfusion; D018572:Disease-Free Survival; D005121:Extremities / Q000473:pathology; D005260:Female; D006801:Humans; D000860:Hypoxia; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008558:Melphalan / Q000493:pharmacokinetics*; D008875:Middle Aged; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008558:Melphalan