title: [Alternative prescription schedules of sunitinib in metastatic kidney cancer: from the underground to the light?].
abstract: Sunitinib was the first targeted therapy improving progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) in the first line of treatment. Classically, sunitinib is administered at a dose of 50 mg/day during four weeks followed by two weeks off (schedule 4/6). This schedule has two pitfalls: intermittent exposure with two weeks "off" and the increase in toxicity during the fourth week. Several alternative prescription schedules were studied with the aim of limiting the intensity of toxicity while maintaining efficacy. This review summarizes the published data on alternative schedules of sunitinib in terms of safety and efficacy. All articles and abstracts on alternative schedule of sunitinib in the mRCC were reviewed. Clinical trials were also searched. Studies evaluating the continuous schedule have not provided evidence of its superiority compared to the 4/6 schedules in terms of activity, tolerance or dose-intensity. Retrospective data of patients treated in a schedule two weeks of treatment "on" one week "off" (schedule 2/3) with sunitinib 50 mg/day show PFS that seem superior to those obtained with a schedule 4/ 6, while having a better safety profile. The alternating schedule of sunitinib 2/3 (50 mg/day) may be a better alternative to schedule 4/6 in terms of tolerance. If toxicity occurs with 50 mg/day on a schedule 4/6, it would probably offer a better alternative in terms of efficiency than dose reduction. The results of ongoing and future studies are expected to prospectively validate the concept.
authors.affiliation: Département d'oncologie, CHU Jean-Minjoz, boulevard Flemming, 25030 Besançon cedex, France, Inserm, UMR1098, 25020 Besançon cedex, France, UMR1098, SFR IBCT, Université de Franche-Comté, 25020 Besançon, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Thiery-Vuillemin
authors.affiliation: Département d'oncologie, CHU Jean-Minjoz, boulevard Flemming, 25030 Besançon cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mouillet
authors.affiliation: Département d'oncologie, CHU Saint-Louis, 75010 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Pouessel
authors.affiliation: Pôle d'oncologie et d'hématologie, Hôpitaux universitaires de Strasbourg, 67091 Strasbourg, France, Inserm U1113, 67037 Strasbourg, France, Fédération de médecine translationnelle, 67085 Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthelemy
authors.affiliation: Oncologie médicale, Centre Galilée, 59045 Lille, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Caty
authors.affiliation: Oncologie médicale, Hôpital Beaujon, 92110 Clichy, France.
authors.forename: Sihem
authors.initials: S
authors.lastname: Sebbagh
authors.affiliation: Oncologie médicale, Hôpital Georges-Pompidou, 75015 Paris, France.
authors.forename: Yann-Alexandre
authors.initials: YA
authors.lastname: Vanno
authors.affiliation: Oncologie médicale polyclinique, 41260 Blois, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Laplaige
authors.affiliation: Oncologie médicale Institut Claudius-Regaud, 31052 Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Cheverau
authors.affiliation: Oncologie médicale, Hôpital Saint-André, 33000 Bordeaux, France, Early Drug Development Certified Unit (Inserm-CIC/INCa), 33075 Bordeaux, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: activity; dose; renal cell carcinoma; schedule; sunitinib; toxicity