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Published on: October 27, 2014
Two-stage phase II study of imatinib mesylate in subjects with refractory or relapsing neuroblastoma
L Calafiore1, L Amoroso, O Della Casa Alberighi
1Department of Hematology-Oncology, Istituto Giannina Gaslini, Genoa.
Background:
Cure rate for subjects with refractory or relapsing metastatic neuroblastoma is <5%. In the search for a novel therapy, continuous daily oral administration of imatinib mesylate was evaluated.
Patients And Methods:
Twenty-four subjects were enrolled in a two-stage study. Imatinib was administered for the first 4 weeks (cycle) at 170 mg/sqm b.i.d. If no major toxicity occurred, the dose was escalated to 300 mg/sqm b.i.d. for a maximum of 12 cycles. Clinical response and toxicity were evaluated according to international criteria. Pharmacokinetics (PK) profiles and tyrosine hydroxylase (TH) mRNA expression were also determined in a subset of subjects.
Results:
Five (21%) complete responses, with one subject still alive at 68 months, and 2 (8%) partial responses lasting up to 29 months were obtained. No grade 4 toxicity was observed. At steady-state, PK exposure (69.7 µg h/ml) was similar to that of adults receiving 1000 mg/die. Responses appear to correlate with the absence or presence of metastasis in the bone marrow (BM) alone, with low TH expression levels at study entry and low imatinib exposure.
Conclusions:
Imatinib mesylate was well-tolerated and effective in the subset of subjects with low BM infiltration as only site of metastasis. Study identifier EudraCT: 2005-005778-63.
Insights
Imatinib mesylate showed effectiveness and good tolerability in treating refractory metastatic neuroblastoma, particularly in patients with limited bone marrow infiltration and low tyrosine hydroxylase expression.
Area of Science:
- Pediatric Oncology
- Pharmacology
- Cancer Therapeutics
Background:
- Refractory or relapsing metastatic neuroblastoma has a poor prognosis with cure rates below 5%.
- Novel therapeutic strategies are urgently needed for this aggressive pediatric cancer.
- Continuous daily oral administration of imatinib mesylate was explored as a potential treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of imatinib mesylate in pediatric patients with refractory or relapsing metastatic neuroblastoma.
- To determine the optimal dosing and toxicity profile of imatinib mesylate in this population.
- To investigate the correlation between pharmacokinetic profiles, gene expression, and clinical response.
Main Methods:
- A two-stage study enrolled 24 subjects with metastatic neuroblastoma.
- Imatinib mesylate was administered orally, starting at 170 mg/sqm b.i.d. and escalating to 300 mg/sqm b.i.d. if tolerated.
- Clinical response, toxicity, pharmacokinetics (PK), and tyrosine hydroxylase (TH) mRNA expression were assessed.
Main Results:
- A 21% complete response rate (CR) and 8% partial response rate (PR) were observed.
- No grade 4 toxicity was reported, indicating good tolerability.
- Responses correlated with minimal bone marrow (BM) infiltration, low TH expression, and lower imatinib exposure.
Conclusions:
- Imatinib mesylate is a well-tolerated and effective treatment option for a subset of metastatic neuroblastoma patients.
- The drug demonstrated particular efficacy in patients with low bone marrow infiltration as the sole metastatic site.
- Further research may refine imatinib use in neuroblastoma based on biomarker expression and disease burden.
