{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:46:32Z","timestamp":1792233992050,"version":"4.4.0"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Older adults with advanced cancer are less likely to tolerate treatment with cytotoxic chemotherapy compared with younger patients due to their aging-related conditions. Hence, oncologists sometimes opt to employ primary treatment modifications (deviation from standard of care) during the first cycle of chemotherapy.<\/jats:p><\/jats:sec>Objective<\/jats:title>To examine the association between primary treatment modification and treatment tolerability in older adults with advanced cancer who were starting new palliative chemotherapy regimens.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cohort study was a secondary analysis of the GAP70+ (Geriatric Assessment Intervention for Reducing Toxicity in Older Patients with Advanced Cancer) trial, which was conducted between July 2014 and March 2019. The GAP70+ trial included patients aged 70 years or older who had advanced (ie, incurable) cancer, had 1 or more geriatric assessment domain impairments, and planned to start a new palliative chemotherapy regimen. Data analysis was conducted in November 2022.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Receipt of standard-of-care chemotherapy regimens vs primary treatment modification defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials (eg, primary dose reduction, schedule change).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Tolerability outcomes were assessed within 3 months of treatment. These outcomes included the following: (1) any grade 3 to 5 toxic effect, according to the National Cancer Institute Common Terminology Criteria for Adverse Events; (2) patient-reported functional decline, defined as the development of worse dependency in activities of daily living using scale scores; and (3) a composite adverse outcome (an end point that combined toxic effects, functional decline, and 6-month overall survival). Multivariable cluster-weighted generalized estimating equation models examined the association between primary treatment modification and outcomes adjusting for covariates.<\/jats:p><\/jats:sec>Results<\/jats:title>This study included 609 patients with a mean (SD) age of 77.2 (5.2) years; more than half (333 [54.7%]) were men. Race and ethnicity was available for 607 patients: 39 (6.4%) were Black, 539 (88.5%) were non-Hispanic White, and 29 (4.8%) were of other race or ethnicity. Nearly half (281 [46.1%]) received a primary modified treatment regimen. The most common cancer types were gastrointestinal cancer (228 [37.4%]) and lung cancer (174 [28.6%]). In multivariable analysis, primary treatment modification was associated with a reduced risk of grade 3 to 5 toxic effects (relative risk [RR],\u20090.85 [95% CI, 0.77-0.94]) and functional decline (RR,\u20090.80 [95% CI, 0.67-0.95]). Patients who received primary treatment modification had 32.0% lower odds of having a worse composite adverse outcome (odds ratio,\u20090.68 [95% CI, 0.48-0.97]).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cohort study, primary treatment modification was associated with improved tolerability of chemotherapeutic regimens among older adults with advanced cancer and aging-related conditions. These findings may help optimize cancer treatment dosing in older adults with advanced cancer and aging-related conditions.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.56106","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T16:00:59Z","timestamp":1708012859000},"page":"e2356106","source":"Crossref","is-referenced-by-count":34,"title":["Primary Treatment Modification and Treatment Tolerability Among Older Chemotherapy Recipients With Advanced Cancer"],"prefix":"10.1001","volume":"7","author":[{"given":"Mostafa R.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, James P. 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