Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic significance on tumor progression.
BACKGROUND
Cancer progression has been associated with neuroendocrine alterations involved in the control of the circadian rhythms, particularly those of cortisol. Moreover, the evidence of an altered cortisol rhythm may predict a poor prognosis in cancer patients. Finally, cancer progression has been proven to be associated with alterations in the pineal gland, which plays a fundamental role in the control of circadian biological rhythms. On this basis, a study was planned to evaluate the effects of a chronic treatment with the pineal hormone melatonin (MLT) in advanced cancer patients with altered cortisol circadian rhythm.


METHODS
The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mg/day orally, in the evening, for 3 consecutive months.


RESULTS
a normalization of cortisol rhythm was achieved in 4/14 (29%) patients. Moreover, stable disease (SD) was obtained in 6/14 (43%) patients under MLT therapy, whereas the other 8 patients had progressive disease (PD). Finally, the percentage of cortisol rhythm normalization achieved in patients with SD was significantly higher than that observed in patients with PD.


CONCLUSIONS
These results show that MLT may normalize cortisol rhythm in advanced cancer patients and this effect appears to be associated with SD, thus confirming the negative prognostic significance of cortisol rhythm alterations in cancer.
Brivio
Fernando
F
Surgical Division, Bassini Hospital, Cinisello Balsamo, Milan, Italy.
Fumagalli
Luca
L
Fumagalli
Gabriele
G
Pescia
Simonetta
S
Brivio
Rinaldo
R
Di Fede
Giuseppe
G
Rovelli
Franco
F
Lissoni
Paolo
P
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage; D001007:Anxiety / Q000188:drug therapy; D001247:Asthenia / Q000188:drug therapy; D002940:Circadian Rhythm / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis
D000975:Antioxidants; D008550:Melatonin; D006854:Hydrocortisone