Activity of temozolomide and bevacizumab in the treatment of locally advanced, recurrent, and metastatic hemangiopericytoma and malignant solitary fibrous tumor

Abstract

Background Hemangiopericytomas and malignant solitary fibrous tumors (HPC/SFT) are rare, closely related sarcomas with unpredictable behavior that respond infrequently to chemotherapy. An optimal systemic treatment strategy for advanced HPC/SFT has not yet been identified. Methods We retrospectively analyzed the records of 14 patients with histopathologically confirmed HPC/SFT who were treated at The University of Texas MD Anderson Cancer Center from May 2005 to June 2007. All patients were treated with temozolomide 150 mg/m2 orally on days 1-7 and days 15-21 and bevacizumab 5 mg/kg intravenously on days 8 and 22, repeated at 28-day intervals. Computer tomographic assessment of tumor size and density (Choi criteria) was used to determine the best response to therapy. The Kaplan-Meier method was used to estimate progression-free survival. Results The median follow-up period was 34 months. Eleven patients (79%) achieved a Choi partial response, with a median time to response of 2.5 months. Two patients (14%) had stable disease as the best response, and one patient (7%) had Choi progressive disease as the best response. The estimated median progression-free survival was 9.7 months with a 6-month progression-free rate of 78.6%. The most frequently observed toxic effect was myelosuppression. Conclusion Combination therapy with temozolomide and bevacizumab is a generally well-tolerated and clinically beneficial regimen for HPC/SFT patients. Additional investigation in a controlled, prospective trial is warranted.

Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

“…Of note, the patient with a Choi response had the best PFS (15 months). Our results seem to suggest a lower level of activity of pazopanib in SFT compared to sunitinib and bevacizumab plus temozolomide [5,6]. Median PFS of patients treated with pazopanib was 3 months, while a retrospective study on sunitinib in 31 SFT patients showed a Choi RR of about 50% with a 6-month median PFS [5].…”

“…Median PFS of patients treated with pazopanib was 3 months, while a retrospective study on sunitinib in 31 SFT patients showed a Choi RR of about 50% with a 6-month median PFS [5]. Again, a Choi RR of 79% with a median PFS of 9.7 months was reported in SFT patients treated with bevacizumab and temozolomide [6]. Interestingly, patients who progressed under pazopanib had dedifferentiated-SFT, while the responsive case carried a malignant-SFT.…”

“…No RECIST responses could be observed but in one patient the effect of pazopanib was marked by a minor (<30%) decrease in tumour size and by a decrease in tumour density, thus classifying for a PR by Choi criteria [11]. As already described for SFT treated with bevacizumab, sunitinib and sorafenib, Choi criteria [4][5][6][7][8][9], originally conceived for GIST receiving imatinib [11], differed from RECIST in assessing response to therapy. Of note, the patient with a Choi response had the best PFS (15 months).…”

“…Very few data are available on the activity of pazopanib in solitary fibrous tumour (SFT), a rare STS subtype [3], the sensitivity of which to antiangiogenics like sorafenib, sunitinib and bevacizumab is reported [4][5][6][7][8][9]. Antiangiogenics were shown to produce durable disease stabilisation in a proportion of patients by means of tumour responses that were mostly non-dimensional [5,6].…”

“…Antiangiogenics were shown to produce durable disease stabilisation in a proportion of patients by means of tumour responses that were mostly non-dimensional [5,6]. We already reported on the activity of pazopanib in a human high-grade dedifferentiated-SFT xenotransplanted into severe combined immunodeficiency (SCID) mice [10].…”