title: Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: the RAINBOW analysis.
abstract: BACKGROUND
  First-line sunitinib is recommended in metastatic renal cell carcinoma (mRCC), but it is frequently associated with relevant toxicities and subsequent dose reductions. Alternative schedules, such as 2-week-on treatment and 1-week-off (2/1 schedule), might improve tolerability. We evaluated the safety and outcomes of this schedule in a large multicenter analysis.
  
  
  METHODS
  Retrospective, multicenter analysis of mRCC patients treated with first-line sunitinib on a 2/1 schedule. Data of 249 patients were reviewed: 208 cases who started sunitinib on the 4/2 schedule (full dosage: 188/208, 90.4%) and thereafter switched to the 2/1 schedule for toxicity (group 4/2 → 2/1) and 41 patients who started first-line sunitinib with the 2/1 schedule because of suboptimal clinical conditions (group 2/1). A total of 211 consecutive patients treated with the 4/2 schedule in another institution served as external controls. Safety was the primary end point. Treatment duration (TD), progression-free survival (PFS) and overall survival (OS) were also analyzed.
  
  
  RESULTS
  In group 4/2 → 2/1, the overall incidence of grade ≥ 3 toxicities was significantly reduced (from 45.7% to 8.2%, P < 0.001) after the switch to 2/1 schedule. This advantage was maintained also in the 106/188 cases (56.4%) who maintained the full dosage. Fatigue, hypertension, hand-foot syndrome and thrombocytopenia were less frequent. The incidence of grade ≥ 3 adverse events in the negatively selected group 2/1 (only 73.2% starting at full dose) was 26.8%, similar to what observed in the external control group (29.4%). Median TD was 28.2 months in the 4/2 → 2/1 group (total time spent with both schedules), 7.8 months in the 2/1 group and 9.7 months in external controls. Median PFS was 30.2, 10.4 and 9.7 months, respectively. Median OS was not reached, 23.2 and 27.8 months, respectively.
  
  
  CONCLUSIONS
  mRCC patients who moved to a modified 2/1 schedule of sunitinib experience an improved safety profile compared with that observed during the initial 4/2 schedule.
authors.affiliation: Ospedale San Donato USL8, Istituto Toscano Tumori (ITT), Arezzo sergio.bracarda@usl8.toscana.it.
authors.forename: S
authors.initials: S
authors.lastname: Bracarda
authors.affiliation: Istituto Nazionale Tumori, Milan.
authors.forename: R
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Clinical Trials Coordinating Center, AOU Careggi, Istituto Toscano Tumori, Florence.
authors.forename: L
authors.initials: L
authors.lastname: Boni
authors.affiliation: Medical Oncology; AORN Cardarelli, Napoli, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Institut Gustave Roussy/Medical Oncology Department, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Derosa
authors.affiliation: Medical Oncology, Ospedale Santa Maria della Misericordia, Perugia.
authors.forename: M
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Polo Oncologico AOU Pisana, Pisa.
authors.forename: L
authors.initials: L
authors.lastname: Galli
authors.affiliation: Istituto Nazionale Tumori, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Procopio
authors.affiliation: Ospedale San Donato USL8, Istituto Toscano Tumori (ITT), Arezzo.
authors.forename: M
authors.initials: M
authors.lastname: Sisani
authors.affiliation: Medical Oncology A, Policlinico Umberto I°, Roma.
authors.forename: F
authors.initials: F
authors.lastname: Longo
authors.affiliation: Medical Oncology, Polytechnic University of the Marche Region, Ancona.
authors.forename: M
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Medical Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo.
authors.forename: F
authors.initials: F
authors.lastname: Morelli
authors.affiliation: Genitourinary Cancers Section, AOU Federico II, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Medical Oncology B, Policlinico Umberto I°, Roma.
authors.forename: A
authors.initials: A
authors.lastname: Altavilla
authors.affiliation: IRCCS San Matteo, Pavia.
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.affiliation: U.O. Oncologia Medica, Ospedale Versilia, Az. USL12, Lido Di Camaiore, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Camerini
authors.affiliation: Institut Gustave Roussy/Medical Oncology Department, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: mRCC; sunitinib; toxicity; treatment schedule