A single daily 400-mg dose of imatinib may be sufficient to induce a therapeutic response in gastrointestinal stromal tumors, and doubling the daily dose can slightly improve progression-free survival, according to an article in the September 25th issue of the Lancet.

Imatinib is approved worldwide for use with gastrointestinal stromal tumors, which do not respond to conventional chemotherapy. Dr. Jaap Verweij and his European and Australasian colleagues studied a total of 946 patients with metastatic disease who were randomized to either imatinib 400 mg once or twice a day.

The primary endpoint was progression-free duration: At roughly two years of follow-up, 50 percent of patients on the higher dose had evidence of disease progression compared with 56 percent of patients on the lower dose. There was no difference in the proportion of patients (99 percent) who reported treatment side effects; the optimum time for therapeutic effect after the start of treatment did not differ between the two groups (around four months).

Dr Verweij commented, “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 favor 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, Dr. Yoichi Kitamura concluded “Although only 4 years have passed since the start of imatinib treatment in gastrointestinal stromal tumors (GIST), worldwide cooperation, as in this EORTC study, has enabled us to share an enormous amount of well-organized information in a short period. This field is progressing phenomenally, and we have to look out for progress on a daily basis.”