Imatinib active against inoperable gastrointesinal stromal
tumours
Imatinib (Glivec) is active against gastrointesinal
stromal tumours (GISTs) and its toxic effects are manageable, results
of a phase I study show.
GISTs are characterised by cell-surface expression
of the tyrosine kinase KIT, which is involved in cell signalling. Imatinib
(approved earlier this year in the United States for treatment of patients
with chronic myeloid leukemia) has been shown to inhibit KIT.
Professor Allan van Oosterom, department of oncology,
Catholic University, Leuven, Belgium, and colleagues carried out a phase
I study to identify the dose-limiting toxic effects of imatinib in 40
patients with advanced soft tissue sarcomas, 36 of whom had GISTs. They
assigned eight patients to receive imatinib 400mg once daily, eight to
receive 300mg twice daily, 16 to receive 400mg twice daily and eight to
receive 500mg twice daily.
Dose-limiting toxic effects were seen at a dose
of 500mg twice daily and included nausea, vomiting, oedema and skin rash.
Doses of 400mg twice daily or less resulted in similar side effects, but
were manageable and only occasionally required dose reductions. Responses
to treatment were seen at all dose levels and objective tumour regression
was seen in 25 of the patients with GISTs. The researchers say that 29
patients were still on treatment after nine months.
The researchers comment that imatinib represents
a significant advance in the treatment of GIST and that the drug is now
being studied in two phase III trials, in which patients are being randomly
assigned to receive 400mg once or twice daily. Investigations are under
way to identify other tumour types in which KIT might be an important
growth factor. "On the grounds of safety data, a dose of up to 400mg twice
daily can be recommended for phase II studies in other solid tumour types;
the duration of treatment remains to be determined," they say (Lancet
2001;358:1421).
Novartis, manufacturer of imatinib, has submitted
an application to the US Food and Drug Administration for the use of imatinib
in patients with inoperable or metastatic malignant GISTs.
Back to Top
|
