http://www.cancercompass.com/cancer-news/1,10493,00.htm
Cancer News
ET-743 Proposed As Novel Agent With Activity In Soft Tissue Sarcomas
March 2, 2006
Ecteinascidin-743 (ET-743) was proposed as a novel chemotherapy agent with activity in soft tissue sarcomas.
"ET-743 is a natural product derived from the marine tunicate Ectenascidia turbinate. ET-743 binds in the minor groove of DNA, blocks transcription factors activity, and traps protein from the nucleotide excision repair system, thus blocking cells in G2-M phase," investigators in France reported.
"ET-743 demonstrated cytotoxic activity at very low concentrations against sarcoma cell lines in preclinical studies. In several phase II clinical studies in patients with advanced sarcoma failing conventional doxorubicin- and ifosfamide-based chemotherapy, ET-743 delivered by continuous intravenous 24-hour infusion at a dose of 1,500 mcg/m2 every 21 days yielded 8% overall response and 30%-40% stabilization rates for a clinical benefit rate close to 40%," explained J. Fayette and colleagues, Hopital Edouard Herriot.
"Interestingly, long-term stabilizations over more than 3 years have been described. In vivo, ET-743 has a specific toxicity profile, the major toxicity of this product being hepatic, through biliary duct destruction, and hematologic. ET-743 has also been evaluated in first-line treatment for these patients. Finally, due to its original mode of action and the lack of cross-resistance with other chemotherapy agents, ET-743 was tested in a preclinical model in combination with other drugs."
The researchers concluded, "Synergy was reported in vitro with doxorubicin and cisplatin; phase I combination studies are in progress."
Fayette and colleagues published their study in Oncologist (ET-743: A novel agent with activity in soft tissue sarcomas. Oncologist, 2005;10(10):827-832).
For additional information, contact J.Y. Blay, Hopital Edouard Herriot, Med Oncology Service, Med Oncology Dept., Pavillon E, 5 Pl Arsonval, F-69003 Lyon, France.
The publisher of the journal Oncologist can be contacted at: Alphamed Press, 318 Blackwell St., Ste. 260, Durham, NC 27701-2884, USA.
Keywords: Lyon, France, Complementary & Alternative Medicine, Chemotherapy, Cisplatin, Clinical Studies, Cytotoxic, Cytotoxic Activity, Doxorubicin Hydrochloride, Cancer Drugs, First Line Treatment, Gastroenterology, Oncology, Pharmaceuticals, Sarcoma, Cancer Therapy, Ecteinascidin 743, Natural Product.
This article was prepared by Biotech Week editors from staff and other reports. Copyright 2006, Biotech Week via NewsRx.com
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New emerging drugs in soft tissue sarcoma.
Milano A, Apice G, Ferrari E, Fazioli F, de Rosa V, de Luna AS, Iaffaioli RV, Caponigro F.
Crit Rev Oncol Hematol. 2006 Mar 10 2006 Mar 10; [Epub ahead of print]
Istituto Nazionale Tumori, Fondazione G. Pascale, Via M. Semmola, 80131 Napoli, Italy.
Doxorubicin and ifosfamide are the two most active drugs in the treatment of patients with advanced, soft tissue sarcoma (STS) of most histologic subtypes, aside from gastrointestinal stromal tumor (GIST). However, after failure of these drugs, alone or in combination, patients with advanced STS have few therapeutic options and the search for new active drugs is well worth pursuing. ET-743, a DNA minor groove binder, which blocks cell cycle progression in G2/M phase through a p53-independent apoptotic process, represents the most promising among novel compounds in STS, since recently completed phase II trials have consistently shown high survival, in spite of the relatively low incidence of major objective responses. The potential for combination with other active compounds further increases the appeal of ET-743. Imatinib mesylate is being tested also in STS other than GIST, which can overexpress one or more of the tyrosine kinases inhibited by imatinib; however, negative data have recently been presented. Clinical studies with a number of other compounds are ongoing or planned. However, investigators involved in the management of patients with advanced STS are to be increasingly aware of the emergence of new molecular targets and genetic profiles in different histologic subtypes, according to which treatment strategies should be adapted.