{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T20:23:43Z","timestamp":1748377423967,"version":"3.40.4"},"reference-count":0,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"published-print":{"date-parts":[[2002]]},"abstract":"<jats:p>Irinotecan and raltitrexed are active against advanced colorectal cancer, act through different mechanisms, and have non-overlapping toxicity profiles. In vitro studies have shown a schedule-dependent synergism between both drugs. The aim of this multicenter study was to determine the maximum tolerated dose (MTD) of this combination. Patients with 5-fluorouracil-refractory, advanced colorectal cancer were eligible. Dose escalation consisted of irinotecan (250\u2013350 mg\/m&lt;sup&gt;2&lt;\/sup&gt; as a 60-min infusion) in combination with a fixed dose of raltitrexed (3\u00a0mg\/m&lt;sup&gt;2&lt;\/sup&gt; as a 15-min infusion, 1 h after irinotecan). Courses were repeated every 21 days. Three to 6 patients were to be included at each dose level. Dose limiting (NCI-CTC grade 3\u20134) toxicities (DLT) were assessed during the first 2 cycles. Thirteen patients were recruited (4, 3 and 6 in levels I, II and III, respectively). Main toxicity was diarrhea and asthenia, whereas myelotoxicity was mild. At level III, 2\/6 patients experienced DLT (grade 4 diarrhea and neutropenia). The MTD was not reached, but further dose escalation was not attempted. Among 12 patients with measurable disease, 2 partial responses were observed for an overall response rate of 17%. The combination of single-agent full doses of irinotecan (350\u00a0mg\/m&lt;sup&gt;2&lt;\/sup&gt;) and raltitrexed (3 mg\/m&lt;sup&gt;2&lt;\/sup&gt;) in a 3-weekly schedule is feasible, with mild toxicity and a promising clinical activity. Diarrhea is the DLT, but it is not more common or severe than that described with irinotecan alone.<\/jats:p>","DOI":"10.1159\/000065719","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T21:05:17Z","timestamp":1050440717000},"page":"42-47","source":"Crossref","is-referenced-by-count":5,"title":["Multicenter Phase I Study of Irinotecan plus Raltitrexed in Patients with 5-Fluorouracil-Refractory Advanced Colorectal Cancer"],"prefix":"10.1159","volume":"63","author":[{"given":"Jorge","family":"Aparicio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram\u00f3n","family":"de las Pe\u00f1as","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Vicent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"Garcer\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Llorca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Maestu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana L.","family":"Yuste","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Farr\u00e9s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2002,8,16]]},"container-title":["Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/65719","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/65719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:08:25Z","timestamp":1745464105000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000065719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2002,8,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000065719","archive":["Portico"],"relation":{},"ISSN":["0030-2414","1423-0232"],"issn-type":[{"type":"print","value":"0030-2414"},{"type":"electronic","value":"1423-0232"}],"subject":[],"published":{"date-parts":[[2002]]}}}