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Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma.

Attia S, Okuno SH, Robinson SI, Webber NP, Indelicato DJ, Jones RL, Bagaria SP, Jones RL, Sherman C, Kozak KR, Cortese CM, McFarland T, Trent JC, Maki RG - Rare Tumors (2015)

Bottom Line: We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor.To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma.This national multi-institutional study is ongoing.

View Article: PubMed Central - PubMed

Affiliation: Mayo Clinic , Jacksonville, FL, USA.

ABSTRACT
We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

No MeSH data available.


Related in: MedlinePlus

Computed tomography of the chest showing three separate lung nodules (Column A: nodule 1; Column B: nodule 2; Column C: nodule 3) at 15 weeks prior to starting pazopanib (first line), receiving temozolomide and CPT-11 (irinotecan); 7 weeks prior to starting pazopanib (second line), on no treatment; one day prior to starting pazopanib (third line); and 21 days after starting pazopanib (fourth line). Nodule 1: 7 weeks pre pazopanib, 5 mm; one day pre pazopanib, 11 mm; 21 days after starting pazopanib, 7.5 mm. Nodule 2: 7 weeks pre pazopanib, 9&6 mm; one day pre pazopanib, 20&19 mm; 21 days after starting pazopanib, 15&10 mm. Nodule 3: 7 weeks pre pazopanib, 14 mm; one day pre pazopanib, 27 mm; 21 days after starting pazopanib, 25 mm.
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fig002: Computed tomography of the chest showing three separate lung nodules (Column A: nodule 1; Column B: nodule 2; Column C: nodule 3) at 15 weeks prior to starting pazopanib (first line), receiving temozolomide and CPT-11 (irinotecan); 7 weeks prior to starting pazopanib (second line), on no treatment; one day prior to starting pazopanib (third line); and 21 days after starting pazopanib (fourth line). Nodule 1: 7 weeks pre pazopanib, 5 mm; one day pre pazopanib, 11 mm; 21 days after starting pazopanib, 7.5 mm. Nodule 2: 7 weeks pre pazopanib, 9&6 mm; one day pre pazopanib, 20&19 mm; 21 days after starting pazopanib, 15&10 mm. Nodule 3: 7 weeks pre pazopanib, 14 mm; one day pre pazopanib, 27 mm; 21 days after starting pazopanib, 25 mm.

Mentions: In early 2011, several months after finishing radiation, new, innumerable bilateral pulmonary nodules were noted on CT. Transbronchial biopsy was histologically consistent with metastasis from Ewing sarcoma (Figure 1D,E). FISH indicated rearrangement involving the EWSR1 gene region. He received cyclophosphamide and topotecan with disease stability noted after two cycles. After six cycles, enlarging lung, new liver and new diffuse sclerotic bony lesions were noted. He then received irinotecan with temozolomide. After two cycles, a dramatic response at all disease sites was noted. Over 10 four-week cycles, spanning a year with treatment breaks, he developed a near complete response with only several subcentimeter bilateral lung nodules remaining. Platelet counts on temozolomide ranged between 50,000 and 75,000. After 10 cycles, the lung nodules began to enlarge minimally (Figure 2). He received another three cycles during which time the lung nodules progressed. This regimen was stopped. He had exhausted all standard treatment lines for Ewing sarcoma, and was not eligible for a clinical study due to thrombocytopenia. Molecular testing on tissue retrieved prior to treatment with temozolomide and irinotecan (Caris, Table 1) was ordered at the patient’s request. The test suggested that only temozolomide and dacarbazine had possible clinical benefit by virtue of loss of O-6-methylguanine DNA methyltransferase expression (Table 1).


Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma.

Attia S, Okuno SH, Robinson SI, Webber NP, Indelicato DJ, Jones RL, Bagaria SP, Jones RL, Sherman C, Kozak KR, Cortese CM, McFarland T, Trent JC, Maki RG - Rare Tumors (2015)

Computed tomography of the chest showing three separate lung nodules (Column A: nodule 1; Column B: nodule 2; Column C: nodule 3) at 15 weeks prior to starting pazopanib (first line), receiving temozolomide and CPT-11 (irinotecan); 7 weeks prior to starting pazopanib (second line), on no treatment; one day prior to starting pazopanib (third line); and 21 days after starting pazopanib (fourth line). Nodule 1: 7 weeks pre pazopanib, 5 mm; one day pre pazopanib, 11 mm; 21 days after starting pazopanib, 7.5 mm. Nodule 2: 7 weeks pre pazopanib, 9&6 mm; one day pre pazopanib, 20&19 mm; 21 days after starting pazopanib, 15&10 mm. Nodule 3: 7 weeks pre pazopanib, 14 mm; one day pre pazopanib, 27 mm; 21 days after starting pazopanib, 25 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508650&req=5

fig002: Computed tomography of the chest showing three separate lung nodules (Column A: nodule 1; Column B: nodule 2; Column C: nodule 3) at 15 weeks prior to starting pazopanib (first line), receiving temozolomide and CPT-11 (irinotecan); 7 weeks prior to starting pazopanib (second line), on no treatment; one day prior to starting pazopanib (third line); and 21 days after starting pazopanib (fourth line). Nodule 1: 7 weeks pre pazopanib, 5 mm; one day pre pazopanib, 11 mm; 21 days after starting pazopanib, 7.5 mm. Nodule 2: 7 weeks pre pazopanib, 9&6 mm; one day pre pazopanib, 20&19 mm; 21 days after starting pazopanib, 15&10 mm. Nodule 3: 7 weeks pre pazopanib, 14 mm; one day pre pazopanib, 27 mm; 21 days after starting pazopanib, 25 mm.
Mentions: In early 2011, several months after finishing radiation, new, innumerable bilateral pulmonary nodules were noted on CT. Transbronchial biopsy was histologically consistent with metastasis from Ewing sarcoma (Figure 1D,E). FISH indicated rearrangement involving the EWSR1 gene region. He received cyclophosphamide and topotecan with disease stability noted after two cycles. After six cycles, enlarging lung, new liver and new diffuse sclerotic bony lesions were noted. He then received irinotecan with temozolomide. After two cycles, a dramatic response at all disease sites was noted. Over 10 four-week cycles, spanning a year with treatment breaks, he developed a near complete response with only several subcentimeter bilateral lung nodules remaining. Platelet counts on temozolomide ranged between 50,000 and 75,000. After 10 cycles, the lung nodules began to enlarge minimally (Figure 2). He received another three cycles during which time the lung nodules progressed. This regimen was stopped. He had exhausted all standard treatment lines for Ewing sarcoma, and was not eligible for a clinical study due to thrombocytopenia. Molecular testing on tissue retrieved prior to treatment with temozolomide and irinotecan (Caris, Table 1) was ordered at the patient’s request. The test suggested that only temozolomide and dacarbazine had possible clinical benefit by virtue of loss of O-6-methylguanine DNA methyltransferase expression (Table 1).

Bottom Line: We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor.To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma.This national multi-institutional study is ongoing.

View Article: PubMed Central - PubMed

Affiliation: Mayo Clinic , Jacksonville, FL, USA.

ABSTRACT
We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

No MeSH data available.


Related in: MedlinePlus