Oxaliplatin may induce cytokine-release syndrome in colorectal cancer patients.
BACKGROUND
Oxaliplatin, a third-generation platinum analogue, is a novel compound with proven anti-tumor activity in colorectal cancer. Moreover, oxaliplatin appears to be relatively well tolerated and easy to handle, even on an outpatient basis.


METHODS
Five advanced colorectal cancer patients treated with oxaliplatin-based chemotherapy developed, after the end of oxaliplatin infusion, similar idiosyncratic reactions characterized by chills, high fever, hypotension, abdominal pain, nausea and often diarrhoea. Venous blood for IL-6 and TNF-alpha assessment was drawn just after the beginning of the reaction and 15 and 30 minutes later. After drawing the third venous sample, intravenous dexamethasone (8 mg) was administered and the drawing of other two venous samples was performed (180 and 360 minutes after the beginning of the reaction).


RESULTS
TNF-alpha and IL-6 serum concentrations significantly decreased after steroid therapy administration. The decrease of TNF-alpha and IL-6 levels went along with the clinical complete regression of symptoms and signs in all the 5 patients. No statistically significant correlation was found between other laboratory parameters and basal cytokine levels or cytokine decrease after steroid therapy.


CONCLUSIONS
Our results clearly show that that idiosyncratic reaction observed in colorectal cancer patients after oxaliplatin infusion may be due to a massive release of cytokines such as TNF-alpha and IL-6. Symptom regression following steroid therapy administration went along with significant decrease of cytokines levels, confirming that TNF-alpha and IL-6 play a role in the pathogenesis of this reaction.
Tonini
G
G
University of Campus Bio-Medico, Rome, Italy.
Santini
D
D
Vincenzi
B
B
Borzomati
D
D
Dicuonzo
G
G
La Cesa
A
A
Onori
N
N
Coppola
R
R
D015746:Abdominal Pain / Q000139:chemically induced / Q000188:drug therapy; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D003907:Dexamethasone / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy; D015850:Interleukin-6 / Q000097:blood; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D016207:Cytokines; D015850:Interleukin-6; D009944:Organoplatinum Compounds; D014409:Tumor Necrosis Factor-alpha; D000077150:Oxaliplatin; D003907:Dexamethasone