A phase II study of chemoneuroimmunotherapy with platinum, subcutaneous low-dose interleukin-2 and the pineal neurohormone mela

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In Vivo. 2002 Mar-Apr;16(2):93-6.
A
phase II study of chemoneuroimmunotherapy with platinum, subcutaneous
low-dose interleukin-2 and the pineal neurohormone melatonin (P.I.M.)
as a second-line therapy in metastatic melanoma patients progressing on
dacarbazine plus interferon-alpha.

Lissoni P, Vaghi M, Ardizzoia A, Malugani F, Fumagalli E, Bordin V, Fumagalli L, Bordoni A, Mengo S, Gardani GS, Tancini G.
Division of Radiation Oncology, San Gerardo Hospital, 20052 Monza, Milani, Italy.
Immunochemotherapeutic
combinations containing IL-2 theoretically represent the most effective
therapies for metastatic melanoma, particularly in association with
cisplatin (CDDP); however, both IL-2 and CDDP have been generally
utilized at high doses, with the consequence of considerable toxicity.
According to psychoneuroimmunological knowledge, the antitumor activity
of IL-2 has been proven to be enhanced by the immunomodulating pineal
neurohormone melatonin (MLT), which has also been shown to increase the
cytotoxicity of cancer chemotherapy and reduce its toxicity.
 
On this
basis, a study was planned with low-dose IL-2 and CDDP in association
with MLT as a second-line therapy for metastatic melanoma patients
progressing on dacarbazine plus interferon-alpha. The study included 13
evaluable patients. CDDP was injected i.v. at 30 mg/m2/day for 3 days
every 21 days. IL-2 was administered s.c. at 3 million IU/day from days
4 to 9 and from days 11 to 16 of the cycle. Finally, MLT was given
orally at 20 mg/day in the evening, every day without interruption.
 
One
patient obtained a complete response (CR), while partial response (PR)
was achieved in 3 other patients. Therefore, the objective tumor
response-rate (CR + PR) was 4 out of 13 (31%). A stable disease
occurred in 5 patients, whereas the remaining 4 patients had a
progressive disease. The treatment was extremely well-tolerated in all
patients and, in particular, no CDDP-related neurotoxicity was
observed.
 
The results of this preliminary study would suggest that
low-dose CDDP and IL-2 in association with the pineal hormone MLT
(P.I.M. schedule), given as a second line therapy, is an effective and
well-tolerated treatment for metastatic melanoma, with a clinical
efficacy at least comparable to that obtained with a first-line therapy
of dacarbazine plus interferon-alpha.