Artesunate in the treatment of metastatic uveal melanoma - first experiences

被引:25
作者
Berger, TG
Dieckmann, D
Efferth, T
Schultz, ES
Funk, JO
Baur, A
Schuler, G
机构
[1] Heidelberg Univ, Ctr Mol Biol, Heidelberg, Germany
[2] Univ Hosp Erlangen, Dept Dermatol, Erlangen, Germany
[3] Global Preclin R&D Merck KgaA, Darmstadt, Germany
[4] Univ Miami, Dept Microbiol & Immunol, Coral Gables, FL 33124 USA
关键词
artesunate; artemisinin; melanoma; uvea; Dacarbazine; Fotemustine; chemotherapy;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile. It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma. We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months. Despite the small number of treated patients, ART might be a promising adjuvant drug for the treatment of melanoma and possibly other tumors in combination with standard chemotherapy. Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future.
引用
收藏
页码:1599 / 1603
页数:5
相关论文
共 26 条
[1]   Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma [J].
Balch, CM ;
Buzaid, AC ;
Soong, SJ ;
Atkins, MB ;
Cascinelli, N ;
Coit, DG ;
Fleming, ID ;
Gershenwald, JE ;
Houghton, A ;
Kirkwood, JM ;
McMasters, KM ;
Mihm, MF ;
Morton, DL ;
Reintgen, DS ;
Ross, MI ;
Sober, A ;
Thompson, JA ;
Thompson, JF .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (16) :3635-3648
[2]   Treatment of disseminated ocular melanoma with sequential fotemustine, interferon α, and interleukin 2 [J].
Becker, JC ;
Terheyden, P ;
Kämpgen, E ;
Wagner, S ;
Neumann, C ;
Schadendorf, D ;
Steinmann, A ;
Wittenberg, G ;
Lieb, W ;
Bröcker, EB .
BRITISH JOURNAL OF CANCER, 2002, 87 (08) :840-845
[3]   Phase III multicenter randomized trial of the dartmouth regimen versus dacarbazine in patients with metastatic melanoma [J].
Chapman, PB ;
Einhorn, LH ;
Meyers, ML ;
Saxman, S ;
Destro, AN ;
Panageas, KS ;
Begg, CB ;
Agarwala, SS ;
Schuchter, LM ;
Ernstoff, MS ;
Houghton, AN ;
Kirkwood, JM .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (09) :2745-2751
[4]   Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro [J].
Chen, HH ;
Zhou, HJ ;
Fan, X .
PHARMACOLOGICAL RESEARCH, 2003, 48 (03) :231-236
[5]   Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron [J].
Efferth, T ;
Benakis, A ;
Romero, MR ;
Tomicic, M ;
Rauh, R ;
Steinbach, D ;
Häfer, R ;
Stamminger, T ;
Oesch, F ;
Kaina, B ;
Marschall, M .
FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (07) :998-1009
[6]   Oxidative stress response of tumor cells: microarray-based comparison between artemisinins and anthracyclines [J].
Efferth, T ;
Oesch, F .
BIOCHEMICAL PHARMACOLOGY, 2004, 68 (01) :3-10
[7]   Molecular modes of action of artesunate in tumor cell lines [J].
Efferth, T ;
Sauerbrey, A ;
Olbrich, A ;
Gebhart, E ;
Rauch, P ;
Weber, HO ;
Hengstler, JG ;
Halatsch, ME ;
Volm, M ;
Tew, KD ;
Ross, DD ;
Funk, JO .
MOLECULAR PHARMACOLOGY, 2003, 64 (02) :382-394
[8]   Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses [J].
Efferth, T ;
Marschall, M ;
Wang, X ;
Huong, SM ;
Hauber, I ;
Olbrich, A ;
Kronschnabl, M ;
Stamminger, T ;
Huang, ES .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2002, 80 (04) :233-242
[9]  
Efferth T, 1996, ARZNEIMITTEL-FORSCH, V46, P196
[10]  
Efferth T, 2001, INT J ONCOL, V18, P767