Pazopanib may be a good option because it appears to target the same proteins that cedaranib targets.
"Pazopanib (GW-786034) is a second-generation multitargeted tyrosine kinase inhibitor against VEGFR-1, 2 and 3, platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-beta and c-kit." -- Expert Opin Investig Drugs. 2008 Feb;17(2):253-61. Sonpavde G, Hutson TE, Sternberg CN. Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. (http://www.ncbi.nlm.nih.gov/pubmed/18230058)
"Cediranib (AZD2171; Recentin, AstraZeneca, Wilmington, Delaware) is a once-daily oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1, 2, and 3, c-KIT, and platelet-derived growth factor receptors." -- J Thorac Oncol. 2008 Jun;3(6 Suppl 2):S131-4. Nikolinakos P, Heymach JV. The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies. (http://www.ncbi.nlm.nih.gov/pubmed/18520296)
Pazopanib
Re: Pazopanib
I looked on the ASCO web-site and found this abstract from the 2007 ASCO Annual Meeting:
Phase II study of pazopanib (GW786034) in patients (pts) with relapsed or refractory soft tissue sarcoma (STS): EORTC 62043.
http://www.asco.org/ASCO/Abstracts+%26+ ... ctID=30612
I also found the Power point presentation of the same study with more information on the CTOS web-site:
http://www.ctos.org/meeting/2007/presentations/875.ppt
there are patients from the other sarcomas group that are not specified by their type of sarcoma, I wonder if any of them where ASPS. If consider all sarcomas pooled, the response rate is lower then in cediranib in ASPS specific study but we do not know what result would cediranib show in non-ASPS group of sarcomas so we can not do any assumption about the expected pazopanib activity in ASPS based on its medium activity in sarcomas. Also it is very important to keep in mind that activity of any drug very often will not translate into the efficacy, the ability to cure or to the increase the life time for the patient. The tumor can shrink and then regrow as the resistance develops and combination trials have more chances to became the cure for ASPS, not only be able to influence its growth for a limited time. Only completed clinical trial with the sufficient follow up time can give an idea if the drug is not only active in ASPS but also prolongs our people life.
Phase II study of pazopanib (GW786034) in patients (pts) with relapsed or refractory soft tissue sarcoma (STS): EORTC 62043.
http://www.asco.org/ASCO/Abstracts+%26+ ... ctID=30612
I also found the Power point presentation of the same study with more information on the CTOS web-site:
http://www.ctos.org/meeting/2007/presentations/875.ppt
there are patients from the other sarcomas group that are not specified by their type of sarcoma, I wonder if any of them where ASPS. If consider all sarcomas pooled, the response rate is lower then in cediranib in ASPS specific study but we do not know what result would cediranib show in non-ASPS group of sarcomas so we can not do any assumption about the expected pazopanib activity in ASPS based on its medium activity in sarcomas. Also it is very important to keep in mind that activity of any drug very often will not translate into the efficacy, the ability to cure or to the increase the life time for the patient. The tumor can shrink and then regrow as the resistance develops and combination trials have more chances to became the cure for ASPS, not only be able to influence its growth for a limited time. Only completed clinical trial with the sufficient follow up time can give an idea if the drug is not only active in ASPS but also prolongs our people life.
Olga
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Fictional
Re: Pazopanib
Hi there- this may be so non-specific as not to be helpful, but we were talking to our oncologist today he said that GSK is planning to open up a phase I of Pazopanib in pediatric sarcomas. He said they were particularly interested in alveolar soft part sarcoma because they have had a partial response in one. If that is true, that is good news.
I did see this reference to Pazopanib in synovial sarcoma from Judson's group: http://www.esmo.org/fileadmin/media/pre ... 02.ppt.pdf
Pazopanib seems to have a reasonable side effect profile and its safety has been study in many other vascular cancers like renal or ovarian CA. Another especially promising thing seems to be its fairly fast onset of action (1/3 partial responses by 12 weeks, 45% stability by 12 weeks) and good durability of response (68 weeks) especially for an anti-angiogenesis agent.
It is made by Glaxo Smith Kline.
I did see this reference to Pazopanib in synovial sarcoma from Judson's group: http://www.esmo.org/fileadmin/media/pre ... 02.ppt.pdf
Pazopanib seems to have a reasonable side effect profile and its safety has been study in many other vascular cancers like renal or ovarian CA. Another especially promising thing seems to be its fairly fast onset of action (1/3 partial responses by 12 weeks, 45% stability by 12 weeks) and good durability of response (68 weeks) especially for an anti-angiogenesis agent.
It is made by Glaxo Smith Kline.
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Fictional
Re: Pazopanib
Just wanted to add that I spoke with our oncologist today about the Pazopanib trial. He heard specifically about a response to pazopanib in Europe. Don't know more details than this. There is a large CTOG phase I trial opening in a week or so....multiple centers including Seattle Childrens. He thought the age went up to 22 years. He thought that enrollment would last 6-9 months.
But for slightly older adults, apparently there is a phase II trial to open almost immediately after - and they lobbied for and won a wider age range for enrollment (he thought up to age 30) because some of the sarcomas (ASPS and synovial sarcoma) were relatively rare.
I haven't looked into this more - because we would like to see how the metronomic is going...(so far so good!) but thought I would post because it is unusual to have trials specifically mentioning ASPS. ASPS' inclusion in pazopanib was because of this responsive case.
But for slightly older adults, apparently there is a phase II trial to open almost immediately after - and they lobbied for and won a wider age range for enrollment (he thought up to age 30) because some of the sarcomas (ASPS and synovial sarcoma) were relatively rare.
I haven't looked into this more - because we would like to see how the metronomic is going...(so far so good!) but thought I would post because it is unusual to have trials specifically mentioning ASPS. ASPS' inclusion in pazopanib was because of this responsive case.