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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Multi-Targeted Kinase Inhibitor Therapy in Pediatric Bone and Soft Tissue Sarcoma Patients-A Single Centre Experience
Anna Mohás1, Klára Horváth1, Zsuzsanna Jakab2
1Pediatric Centre, Tűzoltó Street Department, Semmelweis University, Budapest, Hungary.
Background:
Patients with relapsed or refractory soft tissue and bone sarcomas have dismal outcomes. Multi-targeted kinase inhibitors (mTKI) have proven to be potent agents in several malignancies, both as primer therapy and as a salvage option. Our aim was to evaluate the clinical outcomes of mTKI treatment in a heterogeneous group of pediatric sarcoma patients retrospectively.
Procedures:
A total of 18 patients were treated with sorafenib, regorafenib, or pazopanib; 13 of them had osteosarcoma (OSC), 3 had synovial sarcoma (SySa), and 1-1 patient had chondrosarcoma and rhabdomyosarcoma. Indication for mTKI treatment was primarily progressive, inoperable, relapsed, or chemotherapy-resistant disease after completion of first- and second-line chemotherapy.
Results:
At the time of the beginning of mTKI treatment, the median age was 16.5 years, and the median time to progression from initiation of mTKI was 4 months. The overall response rate was 16%. We conducted a comparison of the survival outcomes of OSC patients receiving mTKIs against a retrospective, non-randomized control group. Overall survival was evaluated from the time of progression or relapse after second-line treatment to the time of death. The log-rank test revealed a significant difference in the survival distribution between patients receiving mTKIs and those who did not (chi2(1) = 8.13 p = 0.004). We observed benefits from mTKI treatment in 3 SySa patients, with pazopanib demonstrating effectiveness and no progression observed thus far.
Conclusions:
Our findings suggest that mTKIs are well-tolerated and can serve as a therapeutic option for refractory bone sarcomas as palliative treatment, aiming to slow disease progression and uphold a good quality of life.
Insights
Multi-targeted kinase inhibitors (mTKIs) show promise for pediatric refractory sarcomas, improving survival outcomes. These agents offer a palliative option, slowing progression and maintaining quality of life in patients with limited treatment choices.
Area of Science:
- Oncology
- Pediatric Hematology/Oncology
- Pharmacology
Background:
- Relapsed or refractory soft tissue and bone sarcomas in pediatric patients have poor prognoses.
- Multi-targeted kinase inhibitors (mTKIs) are effective in various malignancies as both initial and salvage therapies.
Purpose of the Study:
- To retrospectively evaluate the clinical outcomes of multi-targeted kinase inhibitor (mTKI) treatment in a diverse group of pediatric sarcoma patients.
- To assess the efficacy and safety of mTKIs in pediatric patients with relapsed or refractory sarcomas.
Main Methods:
- Eighteen pediatric patients with osteosarcoma, synovial sarcoma, chondrosarcoma, or rhabdomyosarcoma received sorafenib, regorafenib, or pazopanib.
- Treatment was indicated for progressive, inoperable, relapsed, or chemotherapy-resistant disease after first- and second-line chemotherapy.
- Survival outcomes were compared to a retrospective, non-randomized control group for osteosarcoma patients.
Main Results:
- The median age of patients at the start of mTKI treatment was 16.5 years, with a median time to progression of 4 months.
- The overall response rate was 16%.
- A significant difference in survival distribution was observed between osteosarcoma patients receiving mTKIs and controls (p=0.004), indicating improved survival with mTKIs.
Conclusions:
- Multi-targeted kinase inhibitors (mTKIs) are well-tolerated in pediatric sarcoma patients.
- mTKIs represent a viable therapeutic option for refractory bone sarcomas, serving as palliative treatment to slow disease progression.
- Treatment with mTKIs can help maintain a good quality of life for pediatric patients with advanced sarcomas.
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