Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: The RAINBOW analysis

Sergio Bracarda, R. Iacovelli, L. Boni, M. Rizzo, L. Derosa, M. Rossi, L. Galli, G. Procopio, M. Sisani, F. Longo, M. Santoni, F. Morelli, G. Di Lorenzo, A. Altavilla, C. Porta, A. Camerini, B. Escudier, Angelo Martignetti, Riccardo Ricotta, Donatello GasparroRoberto Sabbatini, Giovanni Luca Ceresoli, Alessandra Mosca, Daniele Santini, Claudia Caserta, Luigi Cavanna, Francesco Massari, Teodoro Sava, Corrado Boni, Elena Verzoni, Giacomo Cartenì, Alketa Hamzaj

Research output: Contribution to journalArticlepeer-review

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. Patients and 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.

Original languageEnglish
Article numbermdv315
Pages (from-to)2107-2113
Number of pages7
JournalAnnals of Oncology
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • mRCC
  • Sunitinib
  • Toxicity
  • Treatment schedule

ASJC Scopus subject areas

  • Oncology
  • Hematology

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