title: Practical management of sunitinib toxicities in the treatment of pancreatic neuroendocrine tumors.
abstract: Pancreatic neuroendocrine tumors (pNETs) are infrequent malignancies which manifest in both functional (hormone-secreting) and more commonly non-functional (non-secreting) forms. The oral multitargeted tyrosine kinase inhibitor sunitinib and mammalian target of rapamycin (mTOR) inhibitor everolimus are approved as targeted therapies for patients with well-differentiated, non-resectable disease and evidence of disease progression. The recent approval of sunitinib for the management of advanced pNET is based on a continuous daily dosing (CDD) schedule that differs from the intermittent 4weeks on/2weeks off (4/2) schedule approved for sunitinib in advanced renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). Therefore, although clinicians may be familiar with therapy management approaches for sunitinib in advanced RCC and GIST, there is less available experience for the management of patients with a CDD schedule. Here, we discuss the similarities and differences in the treatment of pNET with sunitinib compared with advanced RCC and GIST. In particular, we focus on the occurrence and management of sunitinib-related toxicity in patients with pNET by drawing on experience in these other malignancies. We aim to provide a relevant and useful guide for clinicians treating patients with pNET covering the management of events such as fatigue, mucositis, hand-foot syndrome, and hypertension.
authors.affiliation: University of Manchester, Manchester Health Sciences Centre and Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK. Electronic address: Juan.Valle@christie.nhs.uk.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Medical Oncology, Beaujon University Hospital (AP-HP) Paris 7 Diderot, Clichy, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hubner
authors.affiliation: Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Grande
authors.affiliation: Medical Oncology, Beaujon University Hospital (AP-HP) Paris 7 Diderot, Clichy, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000628:therapy; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced / Q000628:therapy; D060831:Hand-Foot Syndrome / Q000628:therapy; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D013280:Stomatitis / Q000139:chemically induced / Q000628:therapy; D000077210:Sunitinib; D013959:Thyroid Diseases / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Asthenia; Hand–foot syndrome; Hypertension; Mucositis; Side effects; Skin toxicity