{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T01:19:42Z","timestamp":1772932782829,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T00:00:00Z","timestamp":1683331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA023108"],"award-info":[{"award-number":["P30CA023108"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sunitinib is a multi\u2010target tyrosine kinase inhibitor (TKI) that inhibits VEGF receptor 1, 2, 3 (VEGFRs), platelet\u2010derived growth factor receptor (PDGFR), colony\u2010stimulating factor receptor (CSFR), and the stem cell factor receptor c\u2010KIT. Temsirolimus inhibits mammalian target of rapamycin (mTOR) through binding to intracellular protein FKBP\u201012. Both agents are approved for the treatment of metastatic renal cell carcinoma (mRCC), have different anticancer mechanisms, and non\u2010overlapping toxicities. These attributes form the scientific rationale for sequential combination of these agents. The primary objective of the study was to investigate the efficacy of alternating sunitinib and temsirolimus therapy on progression\u2010free survival (PFS) in mRCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We undertook a phase II, multi\u2010center, single cohort, open\u2010label study in patients with mRCC. Patients were treated with alternating dosing of 4\u2009weeks of sunitinib 50\u2009mg PO daily, followed by 2\u2009weeks rest, then 4\u2009weeks of temsirolimus 25\u2009mg IV weekly, followed by 2\u2009weeks rest (12\u2009weeks total per cycle). The primary endpoint was PFS. Secondary endpoints included clinical response rate and characterization of the toxicity profile of this combination therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nineteen patients were enrolled into the study. The median observed PFS (<jats:italic>n<\/jats:italic>\u2009=\u200913 evaluable for PFS) was 8.8\u2009months (95% CI 6.8\u201325.2\u2009months). Best responses achieved were five partial response, nine stable disease, and three disease progression according to RECIST 1.1 guidelines (two non\u2010evaluable). The most commonly observed toxicities were fatigue, platelet count decrease, creatinine increased, diarrhea, oral mucositis, edema, anemia, rash, hypophosphatemia, dysgeusia, and palmar\u2010plantar erythrodysesthesia syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Alternating sunitinib and temsirolimus did not improve the PFS in patients with mRCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5990","type":"journal-article","created":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T19:34:07Z","timestamp":1683401647000},"page":"13100-13110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A phase <scp>II<\/scp> study of alternating sunitinib and temsirolimus therapy in patients with metastatic renal cell carcinoma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2941-5050","authenticated-orcid":false,"given":"Dylan B.","family":"Ness","sequence":"first","affiliation":[{"name":"Department of Medicine and the Dartmouth Cancer Center at Dartmouth\u2010Hitchcock Medical Center Section of Clinical Pharmacology  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9762-9013","authenticated-orcid":false,"given":"Darcy B.","family":"Pooler","sequence":"additional","affiliation":[{"name":"Department of Medicine and the Dartmouth Cancer Center at Dartmouth\u2010Hitchcock Medical Center Section of Clinical Pharmacology  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-1842","authenticated-orcid":false,"given":"Steven","family":"Ades","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology University of Vermont Cancer Center  Burlington Vermont USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian J.","family":"Highhouse","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology and the Dartmouth Cancer Center at Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bridget M.","family":"Labrie","sequence":"additional","affiliation":[{"name":"Department of Medicine and the Dartmouth Cancer Center at Dartmouth\u2010Hitchcock Medical Center Section of Clinical Pharmacology  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0617-0196","authenticated-orcid":false,"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science and the Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-8914","authenticated-orcid":false,"given":"Jiang","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science and the Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1164-5157","authenticated-orcid":false,"given":"Lionel D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Medicine and the Dartmouth Cancer Center at Dartmouth\u2010Hitchcock Medical Center Section of Clinical Pharmacology  Lebanon New Hampshire USA"},{"name":"Section of Hematology\/Oncology and the Dartmouth Cancer Center at Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-7069","authenticated-orcid":false,"given":"Marc S.","family":"Ernstoff","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology and the Dartmouth Cancer Center at Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis at National Cancer Institute ImmunoOncology Branch  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,6]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"American Cancer Society.Key Statistics About Kidney Cancer. 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