A phase I study of sunitinib in combination with FOLFIRI in patients with untreated metastatic colorectal cancer

N. Starling, F. Vázquez-mazón, D. Cunningham, I. Chau, J. Tabernero, F. J. Ramos, T. J. Iveson, M. P. Saunders, E. Aranda, A. M. Countouriotis, A. Ruiz-garcia, G. Wei, J. M. Tursi, C. Guillen-ponce, A. Carrato

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Background: This study evaluated the maximum tolerated dose (MTD) of sunitinib, a multitargeted tyrosine kinase inhibitor, combined with FOLFIRI (irinotecan 180 mg/m 2 given over 90 min i.v. and l-leucovorin 200 mg/m 2 given over 120 min on day 1, followed by 5-FU 400 mg/m 2 bolus and then 2400 mg/m 2 infused over 46 h) in untreated metastatic colorectal cancer (mCRC).Patients and methods: In this multicentre, phase I, open-label, dose-finding trial, FOLFIRI was administered every 2 weeks. Two sunitinib regimens were explored: Schedule 4/2 (4 weeks on, 2 weeks off; 37.5 and 50 mg/day) and continuous daily dosing (CDD; 37.5 and 25 mg/day). Dose-limiting toxic toxicities (DLTs) were evaluated during weeks 1-6. Efficacy was a secondary objective.Results: Thirty-seven patients were enrolled. The 37.5 mg/day Schedule 4/2 cohort had zero of six DLTs, was expanded by 15 patients and declared the MTD. The MTD was exceeded at all other sunitinib doses and schedules; DLTs included febrile neutropenia (n = 1), grade 4 neutropenia (n = 4) and grade 3 deep vein thrombosis with grade 4 neutropenia (n = 1). At the MTD, non-haematologic grade 3/4 adverse events with a frequency of >10% were diarrhoea, vomiting and lethargy, and the objective response rate was 57.9% (95% confidence interval 33.5-79.7).Conclusions: The MTD of sunitinib combined with FOLFIRI in chemotherapy-naive mCRC was 37.5 mg/day on Schedule 4/2. CDD of sunitinib at 37.5 or 25 mg/day plus FOLFIRI was not feasible. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Original languageEnglish
Article numbermdr046
Pages (from-to)119-127
JournalAnnals of Oncology
Issue number1
Publication statusPublished - 1 Jan 2012


  • Colorectal cancer
  • Pharmacokinetics
  • Sunitinib


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