상위피인용논문
- 조회1,918
Abstract
Tae-You Kim1, Dong-Wan Kim1, Jae-Yong Chung2, Sang Goo Shin2, Sung-Chul Kim3, Dae Seog Heo1, Noe Kyeong Kim1 and Yung-Jue Bang1
1Department of Internal Medicine, and 2 Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine, Seoul, Korea, and 3 Samyang Research Corporation, Salt Lake City, Utah
Abstract
Purpose: The rationale for developing an alternative paclitaxel formulation concerns Cremophor EL-related side effects, and a novel paclitaxel delivery system might augment its therapeutic efficacy. Genexol-PM is a polymeric micelle formulated paclitaxel free of Cremophor EL. A phase I study was performed to determine the maximum tolerated dosage, dose-limiting toxicities, and the pharmacokinetic profile of Genexol-PM in patients with advanced, refractory malignancies.
Experimental Design: Twenty-one patients were entered into the study. Genexol-PM was i.v. administered over 3 h every 3 weeks without premedication. The Genexol-PM dose was escalated from 135 mg/m2 to 390 mg/m2.
Results: All of the patients were evaluable for toxicity and response. Acute hypersensitivity reactions were not observed. Neuropathy and myalgia were the most common toxicities. During cycle 1, grade 3 myalgia occurred in 1 patient at 230 and 300 mg/m2, respectively. At 390 mg/m2, 2 of 3 patients developed grade 4 neutropenia or grade 3 polyneuropathy. Therefore, the maximum tolerated dosage was determined to be 390 mg/m2. There were 3 partial responses (14%) among the 21 patients. Of the 3 responders, 2 were refractory to prior taxane therapy. The paclitaxel area under the curve from time 0 to infinity and peak or maximum paclitaxel concentration seemed to increase with escalating dose, except at 230 mg/m2, which suggests that Genexol-PM has linear pharmacokinetics.
Conclusion: The main dose-limiting toxicities were neuropathy, myalgia, and neutropenia, and the recommended dosage for a phase II study is 300 mg/m2. Genexol-PM is believed to be superior to conventional paclitaxel in terms of the obviation of premedication and the delivery of higher paclitaxel doses without additional toxicity.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Note: This paper was first presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31, 2003.
Requests for reprints: Tae-You Kim, Department of Internal Medicine, Seoul National University College of Medicine, 28, Yongon-dong, Chongno-gu, Seoul, 110-744, Korea. Phone: 82-2-760-2390; Fax: 82-2-762-9662.
Accepted February 25, 1904.
Received November 28, 1903.
Revision received February 17, 1904.
논문정보
- Research article
- 2004년 06월 (BRIC 등록일 )
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
- 120회 이상 인용된 논문
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