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

Autor:	Starling N; Department of Medicine, Royal Marsden Hospital, NHS Foundation Trust, London and Sutton, UK., Vázquez-Mazón F; Medical Oncology Department, Elche University Hospital, Elche., Cunningham D; Department of Medicine, Royal Marsden Hospital, NHS Foundation Trust, London and Sutton, UK. Electronic address: david.cunningham@rmh.nhs.uk., Chau I; Department of Medicine, Royal Marsden Hospital, NHS Foundation Trust, London and Sutton, UK., Tabernero J; Department of Medical Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Ramos FJ; Department of Medical Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Iveson TJ; Department of Medical Oncology, Southampton Oncology Centre, Southampton General Hospital, Southampton., Saunders MP; Department of Radiotherapy and Clinical Oncology, Christie Hospital, Manchester, UK., Aranda E; Department of Medical Oncology, Hospital Universitario Reina Sofia, Cordoba, Spain., Countouriotis AM; Pfizer Oncology, Clinical Development., Ruiz-Garcia A; Pfizer Oncology, Clinical Pharmacology., Wei G; Pfizer Oncology, Oncology Statistics, La Jolla, USA., Tursi JM; Pfizer Italia Srl, Clinical Development Oncology, Milan, Italy., Guillen-Ponce C; Medical Oncology Department, Ramon y Cajal University Hospital, Madrid, Spain., Carrato A; Medical Oncology Department, Ramon y Cajal University Hospital, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2012 Jan; Vol. 23 (1), pp. 119-127. Date of Electronic Publication: 2011 Mar 29.
DOI:	10.1093/annonc/mdr046
Abstrakt:	Background: This study evaluated the maximum tolerated dose (MTD) of sunitinib, a multitargeted tyrosine kinase inhibitor, combined with FOLFIRI (irinotecan 180 mg/m2 given over 90 min i.v. and l-leucovorin 200 mg/m2 given over 120 min on day 1, followed by 5-FU 400 mg/m2 bolus and then 2400 mg/m2 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.
Databáze:	MEDLINE
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