title: Phase I-II study on isolation antiblastic fotemustine perfusion after dacarbazine chemosensitization for advanced melanoma of the extremities.
abstract: Isolation limb perfusion (ILP) is the treatment of choice for locally advanced limb melanoma. With melphalan, the referral drug, complete response (CR) is achieved in about 50% of patients, but significant local toxicity occurs in up to 30%. The aim of the present phase I-II study was to challenge fotemustine (F) in ILP after systemic chemosensitization with dacarbazine (DTIC), given its lower toxicity and greater efficacy, as reported in a previous pilot study. Eleven patients with locally advanced limb melanoma were subdivided into triplets, and given F ILP at escalating doses (starting from 25 mg/l) after intravenous administration of 500 mg/m2 DTIC. Acute and chronic locoregional and systemic toxicity, tumour response and clinical outcome were evaluated. Two patients in the first triplet had G3-G4 local toxicity, so that the scheduled F dosage was halved. At drug levels of 12.5, 15.6 and 18.2 mg/l, local toxicity decreased, but only one of eight patients showed CR. The trial was then interrupted due to the low tolerability and poor efficacy of this perfusion regimen. At present, F ILP after DTIC chemosensitization should not be recommended for the treatment of locally advanced limb melanoma.
authors.affiliation: Clinica Chirurgica II, University of Padova, Padova, Italy. carlor.rossi@unipd.it
authors.forename: C R
authors.initials: CR
authors.lastname: Rossi
authors.forename: F J
authors.initials: FJ
authors.lastname: Lejeune
authors.forename: L
authors.initials: L
authors.lastname: Pontes
authors.forename: M
authors.initials: M
authors.lastname: Foletto
authors.forename: G L
authors.initials: GL
authors.lastname: De Salvo
authors.forename: P L
authors.initials: PL
authors.lastname: Pilati
authors.forename: S
authors.initials: S
authors.lastname: Mocellin
authors.forename: M
authors.initials: M
authors.lastname: Ribeiro
authors.forename: M
authors.initials: M
authors.lastname: Lopes
authors.forename: M
authors.initials: M
authors.lastname: Lise
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D003606:Dacarbazine / Q000008:administration & dosage; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine