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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorVoss, Martin H.
dc.contributor.authorGordon, Michael S.
dc.contributor.authorMita, Monica
dc.contributor.authorRini, Brian
dc.contributor.authorMakker, Vicky
dc.contributor.authorMacarulla Mercadé, Teresa
dc.date.accessioned2021-11-05T06:58:39Z
dc.date.available2021-11-05T06:58:39Z
dc.date.issued2020-11
dc.identifier.citationVoss MH, Gordon MS, Mita M, Rini B, Makker V, Macarulla T, et al. Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer. Br J Cancer. 2020 Nov;123:1590–8.
dc.identifier.issn1532-1827
dc.identifier.urihttp://hdl.handle.net/11351/6503
dc.descriptionCancer therapy; Gynaecological cancer; Urological cancer
dc.description.abstractBackground This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTORC2, in advanced solid tumours. Methods Eligible patients received increasing sapanisertib doses once daily (QD; 31 patients), once weekly (QW; 30 patients), QD for 3 days on/4 days off QW (QD × 3dQW; 33 patients) or QD for 5 days on/2 days off QW (QD × 5dQW; 22 patients). In expansion cohorts, 82 patients with renal cell carcinoma (RCC), endometrial or bladder cancer received sapanisertib 5 mg QD (39 patients), 40 mg QW (26 patients) or 30 mg QW (17 patients). Results Maximum tolerated doses of sapanisertib were 6 mg QD, 40 mg QW, 9 mg QD × 3dQW and 7 mg QD × 5dQW. Frequent dose-limiting toxicities (DLTs) included hyperglycaemia, maculo-papular rash (QD), asthenia and stomatitis (QD × 3dQW/QD × 5dQW); expansion phase doses of 5 mg QD and 30 mg QW were selected based on tolerability beyond the DLT evaluation period. One patient with RCC achieved complete response; nine experienced partial responses (RCC: seven patients; carcinoid tumour/endometrial cancer: one patient each). Sapanisertib pharmacokinetics were time-linear and supported multiple dosing. Pharmacodynamic findings demonstrated treatment-related reductions in TORC1/2 biomarkers. Conclusions Sapanisertib demonstrated a manageable safety profile, with preliminary antitumour activity observed in RCC and endometrial cancer.
dc.language.isoeng
dc.publisherSpringer Nature
dc.relation.ispartofseriesBritish Journal of Cancer;123
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectCàncer - Tractament
dc.subjectMedicaments - Administració
dc.subject.meshNeoplasms
dc.subject.mesh/drug therapy
dc.subject.meshMaximum Tolerated Dose
dc.titlePhase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41416-020-01041-x
dc.subject.decsneoplasias
dc.subject.decs/farmacoterapia
dc.subject.decsdosis máxima tolerada
dc.relation.publishversionhttps://doi.org/10.1038/s41416-020-01041-x
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Voss MH, Makker V] Department of Medicine, 300 East 66th Street, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. [Gordon MS] Oncology Research, HonorHealth Research Institute, 10510 N 92nd St Suite 200, Scottsdale, AZ 85258, USA. [Mita M] Department of Hematology and Oncology, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd North Tower, Los Angeles, CA 90048, USA. [Rini B] Cleveland Clinic Foundation, Department of Solid Tumor Oncology, 9500 Euclid Avenue, Cleveland, OH 44195, USA. [Macarulla T] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.identifier.pmid32913286
dc.identifier.wos000568843200001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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