{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:32:31Z","timestamp":1760189551532},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1994,3]]},"abstract":"PURPOSE<\/jats:title> To determine the toxicities and potential for dose escalation of intravenous (IV) bolus fluorouracil (5-FU) given with 500 mg\/m2\/d leucovorin (LCV) and granulocyte-macrophage colony-stimulating factor (GM-CSF). <\/jats:p><\/jats:sec>PATIENTS AND METHODS<\/jats:title> Thirty-seven patients received escalating doses of 5-FU\/LCV on days 1 to 5 with subcutaneous GM-CSF either 5 or 10 micrograms\/kg\/d starting on day 6 or 3 micrograms\/kg\/d starting on day 1. 5-FU was escalated from 370 mg\/m2\/d by 15% increments between patient cohorts and within patients according to tolerance. <\/jats:p><\/jats:sec>RESULTS<\/jats:title> With GM-CSF starting on day 6, dose-limiting toxicity occurred during cycle no. 1 in all three patients entered at 5-FU 490 mg\/m2\/d. However, individual patients tolerated 5-FU doses up to 644 mg\/m2\/d. When all cycles were analyzed, grade 3 to 4 mucositis and grade 4 granulocytopenia complicated < or = 15% and < or = 6% of cycles with 5-FU doses < or = 560 mg\/m2\/d (115 cycles). With GM-CSF starting on day 1, dose-limiting granulocytopenia occurred during cycle no. 1 in five of 10 patients entered at 5-FU 490 mg\/m2\/d. Although the granulocyte nadirs were significantly lower at each 5-FU dose level with the concurrent GM-CSF schedule (eg, 490 mg\/m2\/d: median, 879\/microL v3,286\/microL; two-tailed P [P2] < .001), dose-limiting granulocytopenia complicated < or = 16% of cycles with 5-FU < or = 560 mg\/m2\/d (99 cycles); > or = grade 3 mucositis occurred in < or = 20% of cycles. Grade 3 to 4 diarrhea was unusual with either GM-CSF schedule. Most patients treated with GM-CSF > or = 5 micrograms\/kg\/d required dose reductions for constitutional toxicity; 3.0 to 3.8 micrograms\/kg\/d was better tolerated. Venous thrombosis occurred in 17% of patients (concurrent v sequential GM-CSF, 29% v 5%; P2 = .08). The median delivered 5-FU dose-intensity for GM-CSF starting either on day 6 or on day 1 was 615 and 647 mg\/m2\/wk (P2 = .41), respectively. Pharmacologic exposure to 5-FU increased with higher doses of 5-FU, and concurrent GM-CSF administration did not affect 5-FU clearance. <\/jats:p><\/jats:sec>CONCLUSION<\/jats:title> A starting dose of 425 mg\/m2\/d of 5-FU with LCV on days 1 to 5 could be safely combined with GM-CSF starting either on day 1 or day 6, with further 5-FU dose escalation according to individual tolerance. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.1994.12.3.560","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T13:09:04Z","timestamp":1487855344000},"page":"560-568","source":"Crossref","is-referenced-by-count":32,"title":["Phase I and pharmacokinetic study of recombinant human granulocyte-macrophage colony-stimulating factor given in combination with fluorouracil plus calcium leucovorin in metastatic gastrointestinal adenocarcinoma."],"prefix":"10.1200","volume":"12","author":[{"given":"J L","family":"Grem","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"McAtee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R F","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Balis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S G","family":"Arbuck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Setser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1994.12.3.560","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T19:56:06Z","timestamp":1653508566000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1994.12.3.560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1994,3]]}},"alternative-id":["10.1200\/JCO.1994.12.3.560"],"URL":"https:\/\/doi.org\/10.1200\/jco.1994.12.3.560","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,3]]}}}