title: Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group) trial.
abstract: PURPOSE: To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM) in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT) vs bioCT. METHODS: A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine) or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular alpha-IFN-2b). Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP), lactate dehydrogenase (LDH), erytrosedimentation rate (ESR), and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site) were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2%) and OS (11 Mo vs 9.5 Mo), all analyses are stratified by treatment arm. RESULTS: In univariate analysis, higher value of lymphocytes percentage (P <.0001), lower value of total leucocytes (P=.005), CRP (P=.003), LHD (P <.0001), ESR (P <.027), fibrinogen (P <.0001), and no liver disease were strongly related to a better survival. In a multivariate analysis, using the Cox proportional hazards model, only fibrinogen (P=.004), LDH (P=.009) and liver disease (P=.04) were found to have an independent role on clinical outcome in metastatic melanoma patients. CONCLUSION: Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used.
authors.affiliation: Department of Medical Oncology, Oncology Institute, Bari, Italy. micguida@libero.it
authors.forename: Michele
authors.initials: M
authors.lastname: Guida
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ravaioli
authors.forename: Vanna Chiarion
authors.initials: VC
authors.lastname: Sileni
authors.forename: Antonella
authors.initials: A
authors.lastname: Romanini
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Antonio
authors.initials: A
authors.lastname: Freschi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Brugnara
authors.forename: Addolorata
authors.initials: A
authors.lastname: Casamassima
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Oriana
authors.initials: O
authors.lastname: Nanni
authors.forename: Ruggero
authors.initials: R
authors.lastname: Ridolfi