{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:07:59Z","timestamp":1765004879131},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Topotecan is a specific inhibitor of topoisomerase I. Preclinical data have indicated that topoisomerase I inhibitors demonstrate more efficacy and have a greater therapeutic index with prolonged continuous exposure. The feasibility of this concept in humans using a 21-day continuous infusion of topotecan has been reported. We conducted a phase II study of this 21-day continuous topotecan administration schedule in patients with locally advanced, unresectable or metastatic colorectal cancer. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Topotecan, initially applied at a dose of 0.6 mg\/m2\/d, was administered as a continuous infusion via an ambulatory pump for 21 days repeated every 4 weeks. The starting dose was reduced to 0.5 mg\/m2\/d, because in five of the first 11 patients, the second course had to be delayed due to prolonged myelosuppression. Forty-two patients entered the study; one patient was ineligible and was excluded from further analyses. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> The overall response rate was 10%, with one complete and three partial responses. The median response duration was 7 months (range, 4 to 11). With this schedule, the major toxicity was prolonged cumulative myelosuppression, including a marked inhibition of erythropoiesis. A total transfusion of 250 U of erythrocytes was needed to maintain a hemoglobin level greater than 6.0 mmol\/L. Other side effects were mild, and included alopecia (47%), periodic nausea (40%)\/vomiting (22%), and fatigue (16%). Pharmacokinetic evaluation showed a mean steady-state plasma concentration (Css) of topotecan of 0.62 ng\/mL (range, 0.33 to 1.1), with a significant relationship between the Css of topotecan and common cytotoxicity criteria (CTC) grade of leukocytopenia. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Topotecan administered as a 21-day continuous infusion exerts minor activity as single-agent therapy in patients with metastatic colorectal cancer. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.1996.14.9.2540","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T13:12:31Z","timestamp":1487855551000},"page":"2540-2545","source":"Crossref","is-referenced-by-count":50,"title":["Phase II and pharmacologic study of topotecan administered as a 21-day continuous infusion to patients with colorectal cancer."],"prefix":"10.1200","volume":"14","author":[{"given":"G J","family":"Creemers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C J","family":"Gerrits","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J H","family":"Schellens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A S","family":"Planting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M E","family":"van der Burg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V M","family":"van Beurden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"de Boer-Dennert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Harteveld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Loos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Stoter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Verweij","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.1996.14.9.2540","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.1996.14.9.2540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,9]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1996,9]]}},"alternative-id":["10.1200\/JCO.1996.14.9.2540"],"URL":"https:\/\/doi.org\/10.1200\/jco.1996.14.9.2540","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,9]]}}}