title: How clinical practice is changing the rules: the sunitinib 2/1 schedule in metastatic renal cell carcinoma.
abstract: Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carcinoma (mRCC). However, with the standard 4/2 schedule (sunitinib 50 mg/day; 4 consecutive weeks on treatment; 2 weeks' rest), 50% of patients require dose reductions to mitigate toxicity, highlighting the need to investigate alternative dosing schedules that improve tolerability without compromising efficacy. Areas covered: We present a concise critical review of published studies comparing the efficacy and safety of the 4/2 and 2/1 schedule (2 weeks on treatment; 1 week rest) for sunitinib. While all studies evaluating the 2/1 schedule have a low level of evidence, the results indicate that the 2/1 schedule improves tolerability compared with the 4/2 schedule, including significant reductions in the incidence of specific adverse events. It was not possible to make any definitive conclusions regarding efficacy due to methodologic limitations of these studies. Expert commentary: In the absence of strong evidence supporting the safety and efficacy of the 2/1 schedule, we recommend that patients should be initiated on sunitinib therapy with the standard 4/2 schedule and only be switched to the 2/1 schedule after the development of dose-limiting toxicities from weeks 3-4 (cycle 1) of the 4/2 schedule cycle.
authors.affiliation: a Ospedale San Donato , USL Toscana Sud-Est , Arezzo , Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bracarda
authors.affiliation: b Leon Berard Cancer Center , Lyon , France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Negrier
authors.affiliation: c Klinikum Oldenburg , Oldenburg , Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Casper
authors.affiliation: d IRCCS San Matteo University Hospital Foundation , Pavia , Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: e Clinical Division of Oncology, Department of Medicine I , Medical University of Vienna , Vienna , Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidinger
authors.affiliation: f Melanoma Unit , The Royal Marsden NHS Foundation Trust , London , UK.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.affiliation: g Department of Medical Oncology , Bergonié Cancer Institute , Bordeaux , France.
authors.forename: Marine
authors.initials: M
authors.lastname: Gross Goupil
authors.affiliation: h Institut Gustave Roussy , Villejuif , France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Angiogenesis inhibitors; dose schedule; renal cell carcinoma; standard of care; sunitinib