{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T13:09:17Z","timestamp":1700226557310},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1989,6]]},"abstract":"<jats:p> A phase I study of mitoxantrone given as a continuous infusion for 21 days using a venous access port and a portable pump was performed. The first dose step was 0.3 mg\/m2\/d for 21 days. Courses were repeated every 6 weeks. Dose increment per step was 0.1 mg\/m2\/d in the first three dose steps and 0.2 mg\/m2\/d in the latter dose steps. Twenty-five patients entered the study and received a total of 50 courses, with a median of two courses (range, one to five). Up to 0.5 mg\/m2\/d, no toxicity (according to the World Health Organization [WHO] criteria) occurred. At 0.7 mg\/m2\/d, one patient experienced grade 2 leukocytopenia and at the 0.9 mg\/m2\/d dose step, one patient experienced grade 2 leukocytopenia, grade 1 thrombocytopenia, and grade 1 hair loss. At 1.1 mg\/m2\/d, two of six patients had grade 3 leukocytopenia, and in one patient treatment was discontinued after two days because of myocardial infarction. In both patients receiving 1.3 mg\/m2\/d, treatment was discontinued after 2 weeks because of grade 3 leukocytopenia. Three patients at the 1.1 mg\/m2\/d, dose step and two patients at the 1.3 mg\/m2\/d dose step experienced some nausea in the last week of the infusion period. One patient developed subclavian vein thrombosis. No infectious complications occurred. Pharmacokinetic studies were performed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Plasma steady-state was reached after 35 hours. During steady-state there was a linear relationship between the mitoxantrone dose administered and the level of mitoxantrone in plasma (r = .93, P less than .005). The mitoxantrone level in leukocytes increased significantly during the infusion period at the 0.9 mg\/m2, the 1.1 mg\/m2, and the 1.3 mg\/m2 dose steps. The area under the curve (AUC) in leukocytes was higher with continuous infusion of 1.1 mg\/m2\/d for 21 days compared with bolus injection of 12 mg\/m2. Mitoxantrone could be detected in plasma for at least five days after the end of the 21-day infusion period and in leukocytes for at least 14 days. Continuous infusion mitoxantrone may increase intracellular drug uptake as expressed by intracellular AUC. We recommend a dose of 1.1 mg\/m2\/d for 3 weeks for evaluation of antitumor efficacy in phase II studies. <\/jats:p>","DOI":"10.1200\/jco.1989.7.6.790","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T18:13:44Z","timestamp":1487873624000},"page":"790-797","source":"Crossref","is-referenced-by-count":27,"title":["A phase I pharmacokinetic study of 21-day continuous infusion mitoxantrone."],"prefix":"10.1200","volume":"7","author":[{"given":"J","family":"Greidanus","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E G","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N H","family":"Mulder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D T","family":"Sleijfer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D R","family":"Uges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Oosterhuis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P H","family":"Willemse","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.1989.7.6.790","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T23:32:42Z","timestamp":1653521562000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1989.7.6.790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,6]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1989,6]]}},"alternative-id":["10.1200\/JCO.1989.7.6.790"],"URL":"https:\/\/doi.org\/10.1200\/jco.1989.7.6.790","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,6]]}}}