{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T04:45:02Z","timestamp":1769575502237,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The single\u2010agent pediatric maximum tolerated dose (MTD) of nab\u2010paclitaxel is significantly higher than adult dosing. We conducted a Phase I trial to establish the MTD\/recommended Phase 2 dose (RP2D) of nab\u2010paclitaxel with gemcitabine in children with relapsed\/refractory solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Nab\u2010paclitaxel was administered intravenously with fixed\u2010dose gemcitabine on days 1, 8, and 15 of 28\u2010day cycles. Three dose levels (DL) of nab\u2010paclitaxel, 180, 210, and 240\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , were evaluated using a rolling six design. Toxicity, nab\u2010paclitaxel pharmacokinetics (PK), and radiologic responses were evaluated. Pretreatment tumor tissue was assessed for SPARC and CAV\u20101.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010four patients enrolled, 22 received therapy, and 20 were evaluable for dose\u2010limiting toxicity (DLT): 17 during dose escalation and 3 in dose expansion at the MTD. Median age was 12.5 years. Diagnoses included osteosarcoma (\n                      <jats:italic>n<\/jats:italic>\n                      = 11), neuroblastoma (\n                      <jats:italic>n<\/jats:italic>\n                      = 4), and rhabdomyosarcoma (\n                      <jats:italic>n<\/jats:italic>\n                      = 4). At the starting dose level (gemcitabine 1000\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , nab\u2010paclitaxel 180\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ), two of five patients experienced DLT, prompting an amendment lowering gemcitabine to 675\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose. Post\u2010amendment, nab\u2010paclitaxel 240\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose with gemcitabine 675\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose was identified as the MTD. Grade \u22653 hematologic toxicities were common. Two patients experienced a partial response (Wilms tumor and osteosarcoma), and PK exhibited linearity across DL. SPARC immunoreactivity was present in most tumors, while CAV\u20101 immunoreactivity was infrequent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The MTD\/RP2D of nab\u2010paclitaxel with gemcitabine in patients with relapsed\/refractory pediatric solid tumors is nab\u2010paclitaxel 240\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose and gemcitabine 675\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose on days 1, 8, and 15 of 28\u2010day cycles; responses were limited in this patient population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.32102","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T06:44:29Z","timestamp":1760510669000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Phase I Trial of Nab\u2010Paclitaxel in Combination With Gemcitabine for Relapsed\/Refractory Pediatric Solid Tumors"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1068-7857","authenticated-orcid":false,"given":"Jonathan","family":"Metts","sequence":"first","affiliation":[{"name":"Cancer and Blood Disorders Institute Johns Hopkins All Children's Hospital  St Petersburg Florida USA"},{"name":"Sarcoma Department H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Ginn","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhulin","family":"He","sequence":"additional","affiliation":[{"name":"Pediatric Biostatistics Core Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohali","family":"Keesari","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane C.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins All Children's Hospital  St Petersburg Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacy","family":"Senn","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Schink","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8372-7149","authenticated-orcid":false,"given":"Samer","family":"Sansil","sequence":"additional","affiliation":[{"name":"Cancer Pharmacokinetics and Pharmacodynamic Core H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pathology Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1128-784X","authenticated-orcid":false,"given":"Thomas","family":"Cash","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta  Atlanta Georgia USA"},{"name":"Department of Pediatrics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.10.4117"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010\u20100265"},{"issue":"12","key":"e_1_2_8_4_1","first-page":"13","article-title":"Gemcitabine and Docetaxel in Metastatic Breast Cancer","volume":"18","author":"Seidman A. 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