Metronomic and metronomic-like therapies in neuroendocrine tumors - Rationale and clinical perspectives.
Metronomic therapy is characterized by the administration of regular low doses of certain drugs with very low toxicity. There have been numerous debates over the empirical approach of this regimen, but fewest side effects are always something to consider in order to improve patients' quality of life. Neuroendocrine tumors (NETs) are rare malignancies relatively slow-growing; therefore their treatment is often chronic, involving several different therapies for tumor growth control. Knowing that these tumors are highly vascularized, the anti-angiogenic aspect is highly regarded as something to be targeted in all patients harboring NETs. Additionally the metronomic schedule has proved to be effective on an immunological level, rendering this approach as a multi-targeted therapy. Rationalizing that advanced NETs are in many cases a chronic disease, with which patients can live for as long as possible, a systemic therapy with regular low doses and a very low toxicity is in many cases a judicious manner of pursuing stabilization. Metronomic schedule is usually correlated with chemotherapy in oncology, but other therapies, such as radiotherapy and biotherapy can be delivered in a metronomic like manner. This review describes clinical trials and case series involving metronomic therapies alone or in combination in patients with advanced NETs. Nowadays level of evidence about metronomic therapy in NETs is quite low, therefore future prospective clinical studies are needed to validate the metronomic approach in specific clinical settings.
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy; Carol Davila University of Medicine and Pharmacy, Endocrinology Department, Bucharest, Romania.
Ioana
I
Lambrescu
Elias University Hospital, Endocrinology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Simona
S
Fica
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy.
Diana
D
Martins
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy.
Francesca
F
Spada
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy.
Chiara
C
Cella
Division of Hepatobiliopancreatic Surgery, IEO, Milan, Italy.
Emilio
E
Bertani
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy.
Manila
M
Rubino
Division of Otolaringology-Head and Neck Surgery, IEO, Milan, Italy.
Bianca
B
Gibelli
Division of Nuclear Medicine, IEO, Milan, Italy.
Chiara
C
Grana
Division of Interventional Radiology, IEO, Milan, Italy.
Guido
G
Bonomo
Division of Radiology, IEO, Milan, Italy.
Luigi
L
Funicelli
Division of Endoscopy, IEO, Milan, Italy.
Davide
D
Ravizza
Division of Pathology, IEO, Milan, Italy.
Eleonora
E
Pisa
Division of Radiotherapy, IEO, Milan, Italy.
Dario
D
Zerini
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy.
Antonio
A
Ungaro
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy. Electronic address: nicola.fazio@ieo.it.
Nicola
N
Fazio
D059250:Administration, Metronomic; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007372:Interferons / Q000008:administration & dosage; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000532:radiotherapy
D000970:Antineoplastic Agents; D007372:Interferons
Anti-angiogenic; Low dose; Metronomic chemotherapy; Metronomic therapy; NET; Neuroendocrine tumors