Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma.
On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil.
Barni
S
S
Divisione di Radioterapia Oncologica, Ospedale S. Gerardo, Monza, Milano, Italy.
Lissoni
P
P
Cazzaniga
M
M
Ardizzoia
A
A
Paolorossi
F
F
Brivio
F
F
Perego
M
M
Tancini
G
G
Conti
A
A
Maestroni
G
G
D000328:Adult; D000368:Aged; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004804:Eosinophils; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007958:Leukocyte Count; D008214:Lymphocytes; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008875:Middle Aged; D019798:Neopterin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin; D008550:Melatonin