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Annals of Oncology Advance Access first published online on January 20, 2007
This version published online on February 23, 2007
Annals of Oncology, doi:10.1093/annonc/mdl481
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© 2007 European Society for Medical Oncology

Gefitinib and irinotecan in patients with fluoropyrimidine-refractory, irinotecan-naive advanced colorectal cancer: a phase I–II study

I Chau1, D Cunningham1,*, T Hickish2, A Massey1, L Higgins1, R Osborne3, N Botwood4 and A Swaisland4

1 Department of Medicine, Royal Marsden Hospital, London and Surrey
2 Department of Oncology, Royal Bournemouth and Poole Hospital, Dorset
3 Department of Oncology, Poole Hospital, Dorset
4 AstraZeneca, Macclesfield, UK

* Correspondence to: Prof D. Cunningham, Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK. Tel: +44-208-661-3156; Fax: +44-208-643-9414; E-mail: david.cunningham{at}rmh.nhs.uk

Background: To establish the recommended dose level (RDL) and to evaluate the efficacy and safety of gefitinib plus irinotecan in patients with advanced fluoropyrimidine-refractory colorectal cancer (CRC).

Patients and methods: Patients with advanced CRC progressing on or within 12 weeks of fluoropyrimidine-based chemotherapy, irinotecan naive and performance status of two or less were recruited. During dose-finding phase, dose-limiting toxicity (DLT) was encountered at dose level 1, therefore subsequent dose de-escalation and pharmacokinetic (PK) studies were carried out. The RDL was then expanded in a multicentre setting to further evaluate safety and efficacy.

Results: From June 2002 to February 2005, 39 patients were treated in total with 27 at the RDL. The RDL was established at irinotecan 225 mg/m2 every 3 weeks and gefitinib 250 mg daily. The DLTs were neutropenia and diarrhoea. For the patients treated at RDL, the objective tumour response rate was 11.1% (95% confidence interval 2.4% to 29.2%) and median survival was 9.3 months. PK studies indicated that the addition of irinotecan to gefitinib resulted in an average of 50% increase in exposure to gefitinib (P < 0.05), but gefitinib did not alter the PK profiles of irinotecan or SN-38. Grade 3–4 toxic effects in all patients included diarrhoea (35.9%), lethargy (15.4%), neutropenia (15.4%), febrile neutropenia (10.3%) and skin rash (7.7%).

Conclusions: Irinotecan and gefitinib at this dose schedule was tolerable, but gefitinib did not appear to add substantial efficacy to irinotecan.

colorectal cancer, epidermal growth factor receptor, gefitinib, irinotecan

Received for publication September 6, 2006. Accepted for publication November 30, 2006.


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[Abstract] [Full Text] [PDF]


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