Results of a randomised trial in this week's issue of THE LANCET suggest that a single daily 400 mg dose of imatinib--known to be a first-choice treatment for gastro-intestinal stromal tumours (GIST)--is sufficient to induce a therapeutic response; a doubling of a daily dose can slightly improve progression-free survival for patients.
Imatinib is approved worldwide for use in GIST, tumours which do not respond to conventional chemotherapy, which have a prevalence of around 20 per 100,000 population. Jaap Verweij (Erasmus University Medical Center, Netherlands) and colleagues from the European Organisation for Research and Treatment of Cancer (EORTC), the Italian Sarcoma Group (IRG), and the australasian Gastrointestinal Trials Group (AGITG) studied 946 patients with metastatic GIST who were randomly allocated either imatinib 400 mg once or twice a day.
50% of patients receiving two doses of imatinib a day, compared with 56% of patients given a single dose, were alive and free of disease progression at around 2 years follow-up. There was no difference in the proportion of patients (99%) who reported treatment side-effects; the optimum time for therapeutic effect after the start of treatment did not differ between the two groups (around 4 months).
Dr Verweij comments: "If the aim of treatment is response induction, a daily dose of 400 mg given for 4–6 months seems to be sufficient. However, in patients with widespread metastatic disease, the prolonged progression-free survival achieved with 400 mg twice daily might lead one to favour this regimen. Whether a similar outcome could be achieved with fewer side-effects by making use of the reduction in drug clearance over time--eg, with a starting dose of 400 mg daily followed by stepwise dose escalation to 400 mg twice a day--is still a matter for further clinical investigations."
In an accompanying commentary (p 1101), Yoichi Kitamura (Tokyo Women's Medical University, Japan) concludes: "Although only 4 years have passed since the start of imatinib treatment in GIST, worldwide cooperation, as in this EORTC study, has enabled us to share an enormous amount of well-organised information in a short period. This field is progressing phenomenally, and we have to look out for progress on a daily basis."
Contact: Dr Jaap Verweij, Department Of Medical Oncology, Erasmus University Medical Center, Groene Hilledijk 301 3075 EA Rotterdam, Netherlands; T) 31-10-439-1338; j.verweij@erasmusmc.nl
Dr Yoichi Kitamura, Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan; T)81-3-3353-8111 ext25217; kitamura@ige.twmu.ac.jp
Journal
The Lancet