title: Metronomic temozolomide as second line treatment for metastatic poorly differentiated pancreatic neuroendocrine carcinoma.
abstract: Neuroendocrine Neoplasms (NEN) are a group of heterogeneous malignancies derived from neuroendocrine cell compartment, with different roles in both endocrine and nervous system. Most NETs have gastroentero-pancreatic (GEP) origin, arising in the foregut, midgut, or hindgut. The 2010 WHO classification divides GEP-NETs into two main subgroups, neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), according with Ki-67 levels. NET are tumors with low (<20 %) Ki-67 value, and NECs, including small cell lung carcinomas and Merkel Cell carcinomas, are all NETs with high Ki-67 levels (>20 %-G3). Poorly differentiated neuroendocrine carcinomas (NEC) are usually treated with cisplatin-based chemotherapy regimens. Here we present a case of a patient with pancreatic NEC progressing after cisplatin and etoposide, treated with temozolomide as palliative, second line treatment. According with the poor Performance Status (PS = 2) and to reduce the toxicity of the treatment was chosen an intermittent dosing regimen of metronomic temozolomide (75 mg/m(2)/day-one-week-on/on-week-off). MGMT resulted methylated. On July 2014 the patient started the treatment. On August 2014 the patient obtained a significant clinical benefit (PS = 0) and the total body CT scan performed on October 2014 showed a RECIST partial response on all the sites of disease. No drug-related side effects were reported by the patient. After 18 months of therapy the treatment continues without significant toxicity, and with further remission of the metastases. Treatment with metronomic "one-week-on/on-week-off" Temozolomide can be considered a good treatment option in patients with poor performance status, affected by pNEC with MGMT methylation.
authors.affiliation: Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: De Divitiis
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: von Arx
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Grimaldi
authors.affiliation: Unit of Interventional Neuroradiology, Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cicala
authors.affiliation: Department of Diagnostic Pathology and Laboratory, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tatangelo
authors.affiliation: IRCCS Neuromed, Località Camerelle, Pozzilli-Isernia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Arcella
authors.affiliation: Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Romano
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Simeone
authors.affiliation: Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy.
authors.forename: R V
authors.initials: RV
authors.lastname: Iaffaioli
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy.
authors.forename: P A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", Naples, Italy. salvatore.tafuto@libero.it.
authors.forename: S
authors.initials: S
authors.lastname: Tafuto
mesh_terms: D059250:Administration, Metronomic; D000818:Animals; D018278:Carcinoma, Neuroendocrine / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D000077204:Temozolomide; D014057:Tomography, X-Ray Computed
chemical_list: D003606:Dacarbazine; D000077204:Temozolomide
keywords: Immunotherapy; Metronomic treatment; Neuroendocrine tumors; Pancreatic neuroendocrine carcinoma; Second line therapy; Temozolomide