{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:34:18Z","timestamp":1787567658771,"version":"build-2736575974"},"reference-count":18,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Sunitinib and pazopanib are administered at fixed doses in patients with metastatic renal cell carcinoma (mRCC), without adjustment for body composition. This study aimed to investigate the association between body mass index (BMI) and treatment-related toxicity and treatment discontinuation in patients with mRCC receiving first-line sunitinib or pazopanib. Methods: A total of 136 patients with mRCC treated with sunitinib (n = 90) or pazopanib (n = 46) were retrospectively evaluated. BMI was compared according to toxicity grade (1\u20132 and 3\u20134) and treatment discontinuation using Student\u2019s t-tests and chi-square\/Fisher\u2019s exact tests. Given the limited number of grade 3\u20134 toxicity events, Firth\u2019s penalized logistic regression was used for multivariable analysis, with adjustment for age, sex, and treatment type. BMI was evaluated as a continuous variable in the primary model and categorically in a supportive analysis. p &lt; 0.05 was considered statistically significant. Results: Higher BMI was significantly associated with grade 1\u20132 (p &lt; 0.001) and grade 3\u20134 toxicity (p &lt; 0.001). In the Firth penalized multivariable analysis, higher BMI remained independently associated with grade 3\u20134 toxicity (OR per 1 kg\/m2 increase, 1.160; 95% CI, 1.057\u20131.283; p = 0.0015). Increasing age (OR per 1-year increase, 1.061; 95% CI, 1.021\u20131.106; p = 0.0022) and sunitinib treatment (OR, 2.629; 95% CI, 1.104\u20136.785; p = 0.028) were also independently associated with grade 3\u20134 toxicity. In the supportive categorical analysis, obesity (BMI \u2265 30 kg\/m2) was associated with higher odds of grade 3\u20134 toxicity compared with BMI &lt; 25 kg\/m2 (OR, 4.173; 95% CI, 1.533\u201311.982; p = 0.005). Conclusions: A higher BMI was associated with a greater likelihood of grade 3\u20134 TKI-related toxicity in patients with mRCC receiving fixed-dose sunitinib or pazopanib. BMI may represent a practical clinical marker for identifying patients who warrant closer toxicity monitoring.<\/jats:p>","DOI":"10.3390\/cancers18172730","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Body Mass Index and Treatment Toxicity in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib or Pazopanib"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-4140","authenticated-orcid":false,"given":"Ahmet K\u00fcr\u015fad","family":"Di\u015fli","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, K\u0131r\u015fehir Education and Research Hospital, K\u0131r\u015fehir 40100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe","family":"Nuransoy Cengiz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammet","family":"Cengiz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kayseri City Hospital, Kayseri 38080, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-4656","authenticated-orcid":false,"given":"\u0130rfan","family":"Bu\u011fday","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kayseri City Hospital, Kayseri 38080, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u0131dvan","family":"G\u00f6n\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3551-5234","authenticated-orcid":false,"given":"Oktay","family":"Bozkurt","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mevl\u00fcde","family":"\u0130nan\u00e7","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metin","family":"\u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.eururo.2018.08.036","article-title":"Epidemiology of Renal Cell Carcinoma","volume":"75","author":"Capitanio","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17009","DOI":"10.1038\/nrdp.2017.9","article-title":"Renal cell carcinoma","volume":"3","author":"Hsieh","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.eururo.2022.06.016","article-title":"The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs\u2014Part A: Renal, Penile, and Testicular Tumours","volume":"82","author":"Moch","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1158\/2159-8290.CD-18-1354","article-title":"The Metabolic Basis of Kidney Cancer","volume":"9","author":"Linehan","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1056\/NEJMra1601333","article-title":"Systemic Therapy for Metastatic Renal-Cell Carcinoma","volume":"376","author":"Choueiri","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"g4797","DOI":"10.1136\/bmj.g4797","article-title":"Renal cell carcinoma","volume":"349","author":"Jonasch","year":"2014","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.annonc.2024.07.727","article-title":"Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial","volume":"35","author":"Tannir","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102994","DOI":"10.1016\/j.esmoop.2024.102994","article-title":"Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended follow-up from the phase III randomised CheckMate 9ER trial","volume":"9","author":"Powles","year":"2024","journal-title":"ESMO Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJMoa065044","article-title":"Sunitinib versus interferon alfa in metastatic renal-cell carcinoma","volume":"356","author":"Motzer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1200\/JCO.22.02622","article-title":"Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial","volume":"41","author":"Sternberg","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1056\/NEJMoa1303989","article-title":"Pazopanib versus sunitinib in metastatic renal-cell carcinoma","volume":"369","author":"Motzer","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Park, J.S., Koo, K.C., Chung, D.Y., Kim, S.I., Kim, J., Oh, C.K., Kim, T.N., Kang, S.K., Park, J.W., and Yoon, Y.E. (2020). Visceral Adiposity as a Significant Predictor of Sunitinib-Induced Dose-Limiting Toxicities and Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12123602"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/bjc.2013.58","article-title":"Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients","volume":"108","author":"Huillard","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00280-009-1170-y","article-title":"Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: Results of a pharmacokinetic\/pharmacodynamic meta-analysis","volume":"66","author":"Houk","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/sj.bjc.6604456","article-title":"Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer","volume":"99","author":"Boven","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1038\/bjc.2014.503","article-title":"Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma","volume":"111","author":"Suttle","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1200\/JCO.2013.50.8267","article-title":"Randomized, Controlled, Double-Blind, Cross-Over Trial Assessing Treatment Preference for Pazopanib Versus Sunitinib in Patients With Metastatic Renal Cell Carcinoma: PISCES Study","volume":"32","author":"Escudier","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115281","DOI":"10.1016\/j.biopha.2023.115281","article-title":"Pharmacokinetics of obese adults: Not only an increase in weight","volume":"166","author":"Gouju","year":"2023","journal-title":"Biomed. Pharmacother."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2730\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:31:44Z","timestamp":1787563904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,23]]},"references-count":18,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172730"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172730","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,23]]}}}