Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors.
Recent evidence has shown that endocrine tumors are under an endocrine and an immune regulation, and that biotherapies with interferon or the long-acting somatostatin analog octreotide may be effective in the control of tumor growth and clinical symptomatology. Within the biotherapies of tumors, interleukin-2(IL-2) has appeared to play an essential role in the antitumor immune response. Despite its important antitumor role, very few studies have been carried out to investigate the possible use of IL-2 in the treatment of advanced endocrine tumors. Its potential toxicity would represent the main limiting factor for the clinical experiments with IL-2. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify the antitumor activity of IL-2, either through immunomodulating mechanisms or through a direct cytostatic activity by inhibiting tumor growth factor production. On this basis, we have performed a phase II pilot study with low-dose IL-2 plus MLT in 14 patients with untreatable endocrine tumors because of disseminated disease, lack of response to previous standard biotherapies or chemotherapies, or tumors for whom no effective therapy is available. Thyroid cancers, carcinoid and endodrine pancreatic tumors were the most frequent neoplasms. IL-2 was given at 3 million IU/day s.c. at 8 p.m. for 6 days/week for 4 weeks, corresponding to one cycle. MLT was given orally at 40 mg/day at 8 p.m. every day. In nonprogressed patients, a second cycle was given after a 21-day rest period. Patients were considered as evaluable when they received at least one complete cycle, and 12 patients were fully evaluable. According to WHO criteria, a partial response was achieved in 3/12 (25%) patients (carcinoid tumor: 1; neuroendocrine lung tumor: 1; pancreatic islet cell tumor: 1). Another patient with gastrinoma had a more than 50% reduction of tumor markers. Toxicity was low in all patients. This preliminary study suggests that low-dose IL-2 immunotherapy in association with the pineal hormone MLT may constitute a new well-tolerated and potentially active therapy of untreatable advanced endocrine tumors.
Division of Radiation Oncology, S. Gerardo Hospital, Monza, Italy.
P
P
Lissoni
S
S
Barni
G
G
Tancini
E
E
Mainini
F
F
Piglia
G J
GJ
Maestroni
A
A
Lewinski
D000008:Abdominal Neoplasms / Q000628:therapy; D000310:Adrenal Gland Neoplasms / Q000628:therapy*; D000328:Adult; D000368:Aged; D002276:Carcinoid Tumor / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D015408:Gastrinoma / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000628:therapy*; D010673:Pheochromocytoma / Q000628:therapy*; D012074:Remission Induction; D013964:Thyroid Neoplasms / Q000628:therapy*
D007376:Interleukin-2; D008550:Melatonin