Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial.

Abstract

BACKGROUND:

Mastocytosis is characterized by the abnormal proliferation of mast cells in 1 or more organs. In most patients, a mutation is present in the gene for C-KIT, resulting in deregulation of the c-kit receptor. Imatinib mesylate is a potent inhibitor of c-kit receptor tyrosine kinase activity. Therefore, the authors evaluated the efficacy and safety of imatinib mesylate as treatment for patients with systemic mastocytosis.

METHODS:

Patients with systemic mastocytosis received imatinib mesylate orally at a dose of 400 mg once daily for 3 to 6 months. Low doses of prednisone were added during the first 2 weeks. Endpoints were reductions in serum tryptase, urinary N-methylhistamine excretion, skin lesions, the number of mast cells in bone marrow sections, hepatomegaly and/or splenomegaly, and symptoms.

RESULTS:

Of 14 patients who were included in the study, 11 patients had the D816V mutation. One patient expressed the FIP1L1-PDGFR-alpha rearrangement gene. In 2 patients, no mutation was found. In 10 patients, serum tryptase levels decreased >20%. In all patients, urinary N-methylhistamine excretion was reduced. In 8 of 13 evaluable patients, the number of mast cells in the bone marrow decreased. Skin symptoms diminished in 5 of 9 patients. Hepatosplenomegaly improved in 3 of 6 patients. Symptoms decreased in 8 of 13 patients. In all patients who had the D816V mutation, reductions in > or =2 endpoints were achieved. In the patient who expressed the FIP1L1-PDGFR-alpha rearrangement gene, a complete response was attained. In general, imatinib mesylate was tolerated well.

CONCLUSIONS:

Imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation.

• Authors: Helga J Droogendijk, Hanneke J C Kluin-Nelemans, Jaap J van Doormaal, Arnold P Oranje, Arjan A van de Loosdrecht, Paul L A van Daele
• Journal: Cancer (Cancer) Vol. 107 Issue 2 Pg. 345-51 (Jul 15 2006) ISSN: 0008-543X [Print] United States
• PMID: 16779792 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents
• Benzamides
• Methylhistamines
• Oncogene Proteins, Fusion
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• mRNA Cleavage and Polyadenylation Factors
• Imatinib Mesylate
• FIP1L1-PDGFRA fusion protein, human
• Proto-Oncogene Proteins c-kit
• Receptor, Platelet-Derived Growth Factor alpha
• N-methylhistamine

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Benzamides
• Bone Marrow Cells (pathology)
• Female
• Humans
• Imatinib Mesylate
• Male
• Mast Cells (pathology)
• Mastocytosis, Systemic (drug therapy, enzymology, genetics)
• Methylhistamines (urine)
• Middle Aged
• Oncogene Proteins, Fusion (genetics)
• Piperazines (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins c-kit (genetics)
• Pyrimidines (therapeutic use)
• Receptor, Platelet-Derived Growth Factor alpha (genetics)
• Recombination, Genetic
• Treatment Outcome
• mRNA Cleavage and Polyadenylation Factors (genetics)