dc.contributor.author | van Meekeren, M | |
dc.contributor.author | Bovee, JVMG | |
dc.contributor.author | van Coevorden, F | |
dc.contributor.author | van Houdt, W | |
dc.contributor.author | Schrage, Y | |
dc.contributor.author | Koenen, AM | |
dc.contributor.author | Miah, AB | |
dc.contributor.author | Zaidi, S | |
dc.contributor.author | Hayes, AJ | |
dc.contributor.author | Thway, K | |
dc.contributor.author | Krol, S | |
dc.contributor.author | Fiocco, M | |
dc.contributor.author | Gelderblom, H | |
dc.contributor.author | Steeghs, N | |
dc.contributor.author | Haas, RL | |
dc.date.accessioned | 2021-12-16T10:40:42Z | |
dc.date.available | 2021-12-16T10:40:42Z | |
dc.date.issued | 2021-09-23 | |
dc.identifier.citation | Acta oncologica (Stockholm, Sweden), 2021, pp. 1 - 8 | |
dc.identifier.issn | 0284-186X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4930 | |
dc.identifier.eissn | 1651-226X | |
dc.identifier.doi | 10.1080/0284186x.2021.1971294 | |
dc.description.abstract | <h4>Purpose</h4>A prior phase I study showed that the neo-adjuvant combination of pazopanib and radiotherapy was well tolerated, and induced promising pathological responses in soft-tissue sarcoma patients. Results of the subsequent prospective, multicenter phase II, PASART-2 trial are presented here, further investigating the efficacy and safety of this combination.<h4>Patients and methods</h4>Patients with high-risk, localized soft-tissue sarcoma received neo-adjuvant radiotherapy, 50 Gy in 25 fractions (PASART-2A) or with a subsequent dose de-escalation to 36 Gy in 18 fractions (PASART-2B). This was combined with 800 mg once daily pazopanib, which started one week before radiotherapy and finished simultaneously. After an interval of 4-8 weeks, surgical resection was performed. The primary endpoint was the rate of pathological complete responses (pCR), defined as ≤5% viable cells.<h4>Results</h4>25 patients were registered in the study, 21 in PASART-2A and 4 in PASART-2B. After central pathology review, the combination treatment led to a pCR in 5 patients (20%). 17 patients (68%) experienced grade 3+ toxicities during neo-adjuvant treatment, of which the most common were alanine aminotransferase (ALT) elevation, aspartate aminotransferase (AST) elevation, and hypertension, all asymptomatic. Grade 3+ acute post-operative toxicities occurred in 5 patients (20%), of which the most common was wound infection. All patients completed the full radiotherapy regimen and underwent surgery. Pazopanib was discontinued before completion in 9 patients (36%), due to elevated ALT and/or AST, and shortly interrupted in 2 patients (8%), due to hypertension.<h4>Conclusion</h4>Apart from asymptomatic hepatotoxicity, the study regimen was well tolerated. Although the pre-specified efficacy endpoint (30% pCR) was not met, a more than doubling of historical pCR rates after neo-adjuvant radiotherapy alone was observed, which warrants further investigation. | en_US |
dc.format | Print-Electronic | |
dc.format.extent | 1 - 8 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | A phase II study on the neo-adjuvant combination of pazopanib and radiotherapy in patients with high-risk, localized soft tissue sarcoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-09-23 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1080/0284186x.2021.1971294 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-09-23 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Acta oncologica (Stockholm, Sweden) | en_US |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Sarcoma and Melanoma Surgery | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Sarcoma and Melanoma Surgery | |
dc.contributor.icrauthor | Hayes, Andrew | |