{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:17:37Z","timestamp":1788985057307,"version":"build-2803163510"},"reference-count":18,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Glob Oncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      The frequent global shortage of leucovorin has raised several concerns. A guided approach is lacking in the guidelines. Data comparing standard-dose (400 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) and reduced-dose (200 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) leucovorin, both administered once on day 1 of each cycle, are unavailable. We plan to assess the efficacy and safety of leucovorin-containing regimens for standard and reduced doses in metastatic colorectal cancer (mCRC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      This retrospective\/prospective observational study was conducted at a tertiary hospital in Saudi Arabia and included data from 2020 to 2025. Adults with mCRC treated with a leucovorin-containing regimen were included. Because of frequent leucovorin shortages, the dose was reduced to 200 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      intravenously given once on day 1 of each cycle. Patients were divided into two groups: leucovorin-400 and leucovorin-200. The study end points were progression-free survival (PFS), response rate, overall survival (OS), and safety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 99 patients were included (50 in the leucovorin-200 group and 49 in the leucovorin-400 group). The FOLFOX6 protocol was given to 67.3% of the overall population. The median PFS was 8 months for the leucovorin-200 group (95% CI, 5.8 to 12.6) and 8.1 months for the leucovorin-400 group (95% CI, 3.9 to 16.3;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .943). Regarding response, 69.3% progressed with leucovorin-400 and 64% with leucovorin-200. The median OS was 71 months in the leucovorin-200 group and was not reached in the leucovorin-400 group (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .336). The incidence of adverse events was similar between the two groups except for grade 1 diarrhea, which occurred in 51% with leucovorin-400 and 18.4% with leucovorin-200 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .001). A total of 1,180 vials were spared after changing the protocol, which correlates with 62,699 Saudi Riyal spared.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The choice between standard-dose and reduced-dose leucovorin may not affect outcomes in the metastatic setting. The reduced dose is a reasonable alternative in cases of drug shortage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/go-26-00140","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:59:16Z","timestamp":1788983956000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Leucovorin Shortage: A Comparison of Standard-Dose Versus Reduced-Dose Leucovorin in Metastatic Colorectal Cancer"],"prefix":"10.1200","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-5561","authenticated-orcid":true,"given":"Jude","family":"Howaidi","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Department, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1817-1046","authenticated-orcid":true,"given":"Fouad","family":"Alnajjar","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Abu Alnasr","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7784-3848","authenticated-orcid":true,"given":"Ahmed S.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhned","family":"Alhumaid","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Salman Bashir","sequence":"additional","affiliation":[{"name":"Research Center, Research Services &amp; Clinical Trial Administration, Scientific Writing &amp; Biostatistics Department, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M.","family":"AlRajhi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, OncoClinicas, Riyadh, Saudi Arabia"},{"name":"Department of Pharmacy Practice, AlFaisal University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_4_2_2","volume-title":"Leucovorin","author":"Hegde VS","year":"2020","unstructured":"Hegde VS, Nagalli S. Leucovorin. Treasure Island, FL: StatPearls Publishing, 2020"},{"key":"e_1_3_4_3_2","volume-title":"Fluorouracil","author":"Casale J","year":"2021","unstructured":"Casale J, Crane JS. Fluorouracil. Treasure Island, FL: StatPearls Publishing, 2021"},{"key":"e_1_3_4_4_2","unstructured":"National Comprehensive Cancer Network: Colon Cancer (Version 2026). NCCN Guidelines 2026"},{"key":"e_1_3_4_5_2","volume-title":"Urgent: Leucovorin Update","author":"US Food and Drug Administration","unstructured":"US Food and Drug Administration: Urgent: Leucovorin Update. FDA. https:\/\/www.fda.gov\/media\/80549\/download"},{"key":"e_1_3_4_6_2","volume-title":"Shortage Drugs List","author":"Saudi Food and Drug Authority","unstructured":"Saudi Food and Drug Authority: Shortage Drugs List. SFDA. https:\/\/www.sfda.gov.sa\/en\/node\/77862"},{"key":"e_1_3_4_7_2","volume-title":"Consultations on the Draft Critical and Vulnerable Drug List. Health Canada Critical and Vulnerable Drug List","author":"Health Canada","unstructured":"Health Canada: Consultations on the Draft Critical and Vulnerable Drug List. Health Canada Critical and Vulnerable Drug List. https:\/\/www.canada.ca\/en\/health-canada\/services\/drugs-health-products\/drug-products\/drug-shortages\/regulations-guidance\/critical-vulnerable-list.html?utm_source=chatgpt.com"},{"key":"e_1_3_4_8_2","first-page":"264","article-title":"Lessons from the leucovorin shortages between 2009 and 2012 in a Medicare advantage population: Where do we go from here?","volume":"7","author":"Hayes MS","year":"2014","unstructured":"Hayes MS, Ward MA, Slabaugh SL, et al: Lessons from the leucovorin shortages between 2009 and 2012 in a Medicare advantage population: Where do we go from here? Am Health Drug Benefits 7:264-270, 2014","journal-title":"Am Health Drug Benefits"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.31.15_suppl.e17566"},{"key":"e_1_3_4_10_2","volume-title":"Prescribing Information. [HIKMA FARMAC\u00caUTICA]","author":"Levoleucovorin","year":"2016","unstructured":"Levoleucovorin: Prescribing Information. [HIKMA FARMAC\u00caUTICA]. 2016. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/206263Orig1s000lbl.pdf"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1Q677"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2005.37.4.212"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02214-5"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.8.2274"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890315)63:6 <1026::AID-CNCR2820631307>3.0.CO;2-R"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.7029"},{"key":"e_1_3_4_17_2","first-page":"e44267","article-title":"The incidence of hematological toxicities in colorectal cancer patients treated with fluoropyrimidine-based regimens at Princess Noorah Oncology Center","volume":"15","author":"Khan M","year":"2023","unstructured":"Khan M, Alharbi S, Aljuhani S, et al: The incidence of hematological toxicities in colorectal cancer patients treated with fluoropyrimidine-based regimens at Princess Noorah Oncology Center. 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