| A phase I study of DHP107, a mucoadhesive lipid form of oral paclitaxel, in patients with advanced solid tumors: Crossover comparisons with intravenous paclitaxel. | |
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MedLine Citation:
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PMID: 22695940 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Purpose This study investigated the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic (PK) profiles of DHP107, a novel oral paclitaxel containing neither Cremophor EL nor P-glycoprotein (P-gp) inhibitor. Patients and methods Patients with advanced solid tumors refractory to all standard treatments were administered a single oral dose of DHP107 on a dose-escalating schedule (60-600 mg/m(2)) during the first chemotherapy cycle, and intravenous paclitaxel 175 mg/m(2) during subsequent cycles. Cohorts of 3 patients were treated at each dose level provided no DLTs were observed. The pharmacokinetics of paclitaxel and its metabolites were investigated for oral DHP107 and intravenous paclitaxel. Results Thirty-four patients were enrolled. Dose-limiting toxicities were not observed, even at the highest dose level (600 mg/m(2)). Further dose escalation was not performed because pharmacokinetics did not increase proportionally at doses above 250 mg/m(2). The coefficient of variance of AUC(last) DHP107 ranged from 11.8 % to 34.0 %, comparable to 24.4 % of intravenous paclitaxel 175 mg/m(2). There were no grade 4 toxicities, whereas grade 3 toxicities included diarrhea (12.1 %), neutropenia (6.1 %) and fatigue (3.0 %). While no objective responses were observed, 11 patients (33.3 %) showed stable disease. Conclusions DHP107 was safe and feasible in patients with advanced malignancies. As exposure of paclitaxel plateau among patients receiving more than 250 mg/m(2) of DHP107, the dose escalation of DHP107 may be limited to 250 mg/m(2) in further clinical trials. |
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Authors:
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Yong Sang Hong; Kyu-Pyo Kim; Hyeong-Seok Lim; Kyun-Seop Bae; Min-Hee Ryu; Jae-Lyun Lee; Heung Moon Chang; Yoon-Koo Kang; Hyeyoun Kim; Tae Won Kim |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-14 |
Journal Detail:
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Title: Investigational new drugs Volume: - ISSN: 1573-0646 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309330 Medline TA: Invest New Drugs Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Poongnap-dong, Songpa-gu, Seoul, 138-736, South Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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