A new study shows that chemotherapy with CSF1R tyrosine kinase inhibitors has anti-tumor activity in patients with inoperable villonodular synovitis. This discovery makes it possible to consider a treatment for patients in a therapeutic impasse.
Pigmented villonodular synovitis, more commonly known as a diffuse-type giant cell tumor, is a rare, locally aggressive tumor caused by overexpression of CSF1.
A team of international researchers has studied the safety and efficacy of a CSF1 R tyrosine kinase inhibitor, nilotinib, in patients with locally advanced, unresectable pigmented villonodular synovitis.
Their results are published The Lancet March 20, 2018.
Nilotinib, a solution for patients with a therapeutic impasse?
In this multicenter, non-comparative phase II trial, the patients came from 4 different countries: France, the Netherlands, Italy and Australia. All suffer from progressive pigmented villonodular synovitis, inoperable or resectable only by mutilating surgery. Their treatment is based on nilotinib, administered twice a day at a dose of 400 mg.
In practice, in 92.6% of 51 patients the disease stopped progressing, but 96% of them, or 54 people, experienced an adverse event related to the treatment. Six patients had at least one adverse event related to grade 3 treatment (headache, dizziness and liver problems, pruritus and drug eruption, diarrhea, increased γ-glutamyl transferase concentration, anorexia and increased headache); but no grade 4 or 5 adverse events were observed.
Only one patient had a serious treatment-related adverse event (drug eruption) and two patients had serious non-drug-related adverse events (borderline ovarian tumor and pilonidal cyst excision).
The need for a randomized trial
The researchers indicate that the disease could be controlled in more than 90% of patients after 12 weeks of treatment with nilotinib. They conclude that CSF1R tyrosine kinase inhibitors have antitumor activity with manageable toxicity in patients with inoperable progressive pigmented villonodular synovitis.
However, they consider it necessary to conduct randomized trials on the efficacy of nilotinib in patients with unresectable pigmented villonodular synovitis.
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