Basal level and behaviour of cytokines in a randomized outpatient trial comparing chemotherapy and biochemotherapy in metastatic melanoma.
Cytokines play a crucial role in the host's immune response. In melanoma patients, cytokine profiles seems to be related to the clinical course and their imbalance could be associated to tumour progression. Thus, we studied a panel of baseline cytokines and their behaviour during treatment in order to verify their correlation with clinical outcomes. Interleukin-6, interleukin-8, interleukin-10, interleukin-12 and soluble receptor of interleukin-2 were evaluated in 90 out of 176 metastatic melanoma patients enrolled in a phase III study comparing chemotherapy and biochemotherapy. We divided patients into three different groups according to their own cytokine levels (low, intermediate and high) and then we correlated these groups with some clinical features. We also monitored the cytokines during the treatment in a subgroup of 37 patients. In univariate analysis, higher values of interleukin-6 (P = 0.005), soluble receptor of interleukin-2 (P = 0.001) and interleukin-12 (P = 0.010) were correlated with a worse survival. Conversely, interleukin-8 was unable to discriminate patients with different prognoses, and interleukin-10 was undetectable in the majority of patients. In multivariate analysis, only soluble receptor of interleukin-2 maintained its independent role in survival. The impact of baseline cytokines on response was insignificant. Regarding the behaviours of cytokines during treatment, the most remarkable aspect was a progressive increase of interleukin-12 and soluble receptor of interleukin-2 in patients with a better survival. In our metastatic melanoma patients, higher basal levels of interleukin-6, interleukin-12 and soluble receptor of interleukin-2 were associated with a worse survival. In contrast, a progressive increase of interleukin-12 and soluble receptor of interleukin-2 was observed during treatment in patients with a better survival.
Guida
Michele
M
Oncology Division, Immunology Laboratory, Istituto Oncologico, Bari bImmunotherapy Unit, Oncology Department, Pierantoni Hospital, Forlì, Italy. micguida@libero.it
Riccobon
Angela
A
Biasco
Guido
G
Ravaioli
Alessandra
A
Casamassima
Addolorata
A
Freschi
Andrea
A
Palma
Maurizio Dalla
MD
Galligioni
Enzo
E
Nortilli
Rolando
R
Chiarion-Sileni
Vanna
V
Picozzo
Jacopo
J
Romanini
Antonella
A
Nanni
Oriana
O
Ridolfi
Ruggero
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism*; D003606:Dacarbazine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage
D016207:Cytokines; D007155:Immunologic Factors; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D019947:Receptors, Interleukin-6; D016753:Interleukin-10; D018664:Interleukin-12; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin