Pharmaco-immunological Study of Interferon-alpha and Metronomic Cyclophosphamide Association in Neuroendocrine Tumors

Inclusion Criteria: * performance status ECOG-WHO ≤ 1 * histologically proved neuroendocrine tumor with Ki67 \< or = 10%, metastatic or locally advanced without surgery possibility * at least one measurable lesion based on RECIST criteria version 1.1 * signed written informed consent Exclusion Criteria: * previous treatment with interferon or cyclophosphamide * treatment by immunosuppressive drugs * diabetes complicated by coronary artery disease or vasculopathy * severe respiratory failure, chronic respiratory failure, COPD * history of severe heart failure * severe renal or hepatic impairment * diabetes complicated with coronary artery disease or vasculopathy * alcoholism unweaned * uncontrolled epilepsy and/or achievement of the central nervous system functions * history of severe depressive syndrome * presence or history of severe psychiatric condition, particularly severe depression, suicidal thoughts or attempted suicide * decompensated liver cirrhosis * severe myelosuppression * psoriasis and sarcoidosis * active disease condition or uncontrolled infection * association with the yellow fever vaccine * association with phenytoin in prophylaxis * hypersensitivity against interferon or cyclophosphamide * prior history of other malignancy except for: basal cell carcinoma of the skin, cervical intra-epithelial neoplasia and other cancer curatively treated with no evidence of disease for at least 3 years * pregnancy, breast-feeding or absence of adequate contraception for fertile patients * patients under guardianship, curatorship or under the protection of justice