In Vivo March 1, 2010 vol. 24 no. 2 239-241

Synchronization of Cortisol Circadian Rhythm by the Pineal Hormone Melatonin in Untreatable Metastatic Solid Tumor Patients and its Possibile Prognostic Significance
on Tumor Progression

Research Article (download PDF version – complete)

FERNANDO BRIVIO1, LUCA FUMAGALLI1, GABRIELE FUMAGALLI2, SIMONETTA PESCIA2, RINALDO BRIVIO2, GIUSEPPE DI FEDE3, FRANCO ROVELLI2 and PAOLO LISSONI3

1 Surgical Division, Bassini Hospital, Cinisello Balsamo, Milan, Italy
2 Department of Clinical Pathology, S.Gerardo Hospital, Monza, Italy
3 Institute of Biological Medicine, Milan, Italy

*Correspondence: Dr. Paolo Lissoni, Divisione di Radioterapia Oncologica, Ospedale S.Gerardo, 20052 Monza, Milano, Italy; Fax: +390392332284, e-mail: p.lissoni@hsgerardo.org

Abstract
The present study was carried out to evaluate the influence of a short-period IL-2 administration on the efficacy of chemotherapy in metastatic colorectal cancer patients with pretreatment lymphocytopenia, which was defined as a lymphocyte count of less than 1500/mm3.

The study included 144 consecutive metastatic colorectal cancer patients, who underwent chemotherapy with oxaliplatin plus 5-fluorouracil. Lymphocytopenia was seen in 41/144 (28%) patients, who were randomized to receive chemotherapy alone or chemotherapy after a prechemoimmunotherapy with IL-2 (3 MIU twice/day for 3 consecutive days), whereas patients with a normal pretreatment lymphocyte count received only chemotherapy.

A normalization of the lymphocyte number was achieved in 12/19 lymphocytopenic patients pretreated with IL-2. The objective tumor regression rate achieved in patients with a normal lymphocyte count prior to chemotherapy was significantly higher compared to that obtained in lymphocytopenic patients treated with chemotherapy alone (54/103 vs. 3/22, p<0.01), whereas no significant difference occurred between patients with normal lymphocyte count and lymphocytopenic patients pretreated with IL-2 (54/103 vs. 8/19).

This study confirms that pretreatment lymphocytopenia is associated with reduced efficacy of chemotherapy in metastatic colorectal cancer patients. Moreover, it suggests that pretreatment with IL-2 before the onset of chemotherapy may enhance the efficacy of chemotherapy in lymphocytopenic patients. Therefore, the administration of IL-2 before the onset of chemotherapy to improve the immune status of cancer patients may be considered as a new chemoimmunotherapeutic combination, which may be recommended in the treatment of advanced cancer patients, particularly in those with cancer-related immune alterations.

http://www.imbio.it/wp-content/uploads/2013/10/100430_synchronization_cortisol_circadian_rhythm.pdf(download PDF version – complete)