Francesca Spada1, Patrick Maisonneuve2, Caterina Fumagalli3, Riccardo Marconcini4, Fabio Gelsomino5, Lorenzo Antonuzzo6, Davide Campana7, Ivana Puliafito8, Giulio Rossi9, Pinuccia Faviana10, Luca Messerini11, Massimo Barberis3, Nicola Fazio12. 1. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. 2. Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. 3. Histopathology and Molecular Diagnostics Unit, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. 4. Department of Oncology 2, Santa Chiara Hospital, Via Roma 67, 56100, Pisa, Italy. 5. Division of Oncology, Department of Oncology and Hematology, University Hospital, Via del Pozzo 70, 41100, Modena, Italy. 6. Medical Oncology 1, AOU Careggi Hospital, Viale Pieraccini 17, 50139, Firenze, Italy. 7. Scienze Mediche e Chirurgiche, Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy. 8. Oncologia Medica, Istituto Oncologico del Mediterraneo (IOM), Via Penninazzo 7, 95029, Viagrande, Italy. 9. Anatomia Patologica, Azienda USL Romagna, Ospedale S. Maria delle Croci, Viale Randi 5, 48121, Ravenna, Italy. 10. Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Paradisa 2, 56126, Pisa, Italy. 11. Division of Human Pathology, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Firenze, Italy. 12. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. nicola.fazio@ieo.it.
Abstract
PURPOSE: Temozolomide (TEM) has been reported to be active alone or in combination with capecitabine (CAP) in patients with neuroendocrine neoplasms (NENs). We retrospectively evaluated activity and toxicity of TEM-based chemotherapy in patients with advanced NENs and explored the potential correlation with clinical/biological factors. METHODS: Patients received oral TEM alone or in combination with CAP. Objective response rate (ORR) [complete response + partial response (PR)], median progression-free survival (mPFS), and toxicity were calculated. The O6-methylguanine-DNA-methyltransferase (MGMT) gene inactivation status in tumor tissue was evaluated by pyrosequencing. RESULTS: From September 2008 to April 2020, 170 patients (84% progressive on different therapies) were consecutively treated, 114 (67%) patients received TEM-CAP and 56 (33%) TEM alone. Primary tumor sites were: pancreas 98 (58%), gastrointestinal tract 21 (12%), lung 35 (21%), and unknown 16 (9%). The ORR was 28% for the whole population (33% for TEM-CAP and 18% for TEM as single agent). The median OS (mOS) and mPFS of the whole population were 35.6 months (32.6-48.7) and 14.7 months (10.1-18.3), respectively. There were 48% PR in the MGMT hypermethylated, mainly in pancreatic NENs. Vomiting and leukopenia were the most frequent grade 3/4 toxicity. CONCLUSIONS: This large retrospective analysis suggested that a TEM-based chemotherapy is active in advanced, pretreated NEN patients. It generated solid hypotheses that warrant a future prospective study in a biological homogeneous NEN population and clinical setting.
PURPOSE:Temozolomide (TEM) has been reported to be active alone or in combination with capecitabine (CAP) in patients with neuroendocrine neoplasms (NENs). We retrospectively evaluated activity and toxicity of TEM-based chemotherapy in patients with advanced NENs and explored the potential correlation with clinical/biological factors. METHODS:Patients received oral TEM alone or in combination with CAP. Objective response rate (ORR) [complete response + partial response (PR)], median progression-free survival (mPFS), and toxicity were calculated. The O6-methylguanine-DNA-methyltransferase (MGMT) gene inactivation status in tumor tissue was evaluated by pyrosequencing. RESULTS: From September 2008 to April 2020, 170 patients (84% progressive on different therapies) were consecutively treated, 114 (67%) patients received TEM-CAP and 56 (33%) TEM alone. Primary tumor sites were: pancreas 98 (58%), gastrointestinal tract 21 (12%), lung 35 (21%), and unknown 16 (9%). The ORR was 28% for the whole population (33% for TEM-CAP and 18% for TEM as single agent). The median OS (mOS) and mPFS of the whole population were 35.6 months (32.6-48.7) and 14.7 months (10.1-18.3), respectively. There were 48% PR in the MGMT hypermethylated, mainly in pancreatic NENs. Vomiting and leukopenia were the most frequent grade 3/4 toxicity. CONCLUSIONS: This large retrospective analysis suggested that a TEM-based chemotherapy is active in advanced, pretreated NEN patients. It generated solid hypotheses that warrant a future prospective study in a biological homogeneous NEN population and clinical setting.
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