Trabectedin用于对铂金类药物有反应之卵巢癌病患有效

　　November 10, 2006（纽约讯）—一项第二期临床试验结果确认了之前的研究，显示一个研究中药物trabectedin（Yondelis, PharmaMar与Johnson & Johnson药厂制造）是有效、耐受性良好的，且其所引发的不良反应是能够处理的；这项发表于化学治疗基金会第24次研讨会的研究结果，对铂金类药物有反应之再发性卵巢癌病患具有重要意义；座谈会共同主席，来自纽约大学医学院的Franco Muggia医师向Medscape表示，这是个令人兴奋的药物，该药物是个重要的替代药物，且其所引起的不良反应与其他药物不同。
　　
　　Trabectedin是一种来自海洋的生物碱，会与DNA结合，摺叠DNA螺旋、并诱发细胞凋亡以及细胞周期停止；这项最新的随机分派、开放标记、多中心研究目的在评估该药物以两种不同投予剂量的客观反应率，该试验次要目标在评估反应维持时间、CA-125反应、以及恶化时间及安全性。
　　
　　总共有23个中心加入，共收纳107位病患，罹患再发性卵巢恶性肿瘤妇女接受1.3 mg/㎡的trabectedin持续输注3小时，或1.5 mg/㎡的trabectedin持续输注24小时，这两种剂量疗程皆每3个星期投予一次，且所有病患事先接受dexamethasone治疗。
　　
　　来自西班牙巴塞隆纳Vall d'Hebron综合医院的主要作者Jose del Campo医师在会议中发表这项研究结果，这两种治疗疗程显然是有效的、1.3-mg/㎡持续输注3小时的客观反应率为28.3%、1.5-mg/㎡持续输注24小时的反应率为29.6%。
　　
　　座谈会共同主席、来自伊色列Tel Aviv Sourasky医学中心的Tamar Safra医师在讨论中表示，我对于使用最具有毒性的剂量但不一定是最有效的感到高兴，就像在这个研究中所见到的一样；del Campo博士的研究团队同样也证实CA-125是整体反应的一个良好指标。
　　
　　CA-125反应
　　

组别	输注 3 小时 1.3 m g/ ㎡ , n = 54 (%)	输注 24 小时 1.5 m g/ ㎡ , n = 52 (%)
CA-125 50% 无反应者	38 (73.1)	38 (70.4)
CA-125 50% 具反应者	14 (26.9)	16 (29.6)

　　
　　研究者发现，达到客观反应时间中位数为5.4个月；持续输注3小时组恶化所需时间为5.6个月，相较于持续输注24个月组则是5.7个月。
　　
　　del Campo博士表示，最常见与药物相关的不良反应为恶心、疲劳、呕吐与便秘；与之前的经验相符，他表示，秃头、胃炎与神经毒性是非常少见的，就算发生通常也是轻至中度的。
　　
　　在与Medsacpe的访谈中，Muggia博士称赞这项研究结果证实了对于治疗反应不佳的病患仍有进步的空间，许多使用于治疗卵巢癌的药物都因为神经毒性而受限，因此，当疾病再发时，能够进行的治疗相当有限；例如trabectedin这样显然较不会造成神经毒性的药物，会是个有希望的应用；下一步将是研究结合trabectedin与其他药物的疗效。

Trabectedin Effective in Platinum-Sensitive Ovarian Cancer Patients

By Allison Gandey
Medscape Medical News

November 10, 2006 (New York) –- A new phase 2 trial has confirmed the findings of previous trials showing that the investigational drug trabectedin (Yondelis, PharmaMar and Johnson & Johnson) is active and well tolerated, with manageable toxicity. The results, presented here at the Chemotherapy Foundation Symposium XXIV, could have important implications for platinum-sensitive patients with relapsed ovarian cancer. "It is an exciting agent," session cochair Franco Muggia, MD, from the New York University School of Medicine, told Medscape. "It represents an important alternative, and the toxicity spectrum is quite different."

Trabectedin is a marine alkaloid that binds to the minor groove of DNA, bending the helix and inducing apoptosis and cell cycle arrest. The purpose of this latest randomized, open-label, multicenter study was to assess the objective response rate of the drug administered in 2 dosing schedules. The secondary goals of the trial were to evaluate response duration, CA-125 response, time to progression, and safety.

A total of 107 patients were enrolled in 23 centers. The women with recurrent ovarian carcinoma received either 1.3 mg/m² of trabectedin over a 3-hour infusion or 1.5 mg/m² over a 24-hour infusion. Both doses were administered every 3 weeks, and all patients received dexamethasone beforehand.

Presenting the group's findings at the meeting, lead investigator Jose del Campo, MD, from the Hospital General Vall d'Hebron, in Barcelona, Spain, said, "Both schedules appear active, with 28.3% and 29.6% objective response rates in the 3-hour, 1.3-mg/m² and the 24-hour, 1.5-mg/m² regimens."

"I'm happy to see that the most toxic dose is not always the most effective, as was the case in this trial," session cochair Tamar Safra, MD, from the Tel Aviv Sourasky Medical Center, in Israel, commented during the discussion period about the study. Dr. del Campo's team also showed that CA-125 was a good indicator of overall response.

CA-125 Responders

Group	3-hour 1.3 mg/m2, n = 54 (%)	24-hour 1.5 mg/m2, n = 52 (%)
CA-125 50% nonresponder	38 (73.1)	38 (70.4)
CA-125 50% responder	14 (26.9)	16 (29.6)

The researchers found that median duration of objective response was 5.4 months. The time to progression was 5.6 months in the 3-hour-infusion group and 5.7 months in the 24-hour-infusion group.

Dr. del Campo reported that the most common drug-related adverse events were nausea, fatigue, vomiting, and constipation. Consistent with previous experience, he showed that alopecia, stomatitis, and neurotoxicity were uncommon and mild or moderate when they did occur.

During an interview with Medscape, Dr. Muggia praised the findings for confirming "substantial activity" in a difficult subset of patients. "Many of the drugs in ovarian cancer are limited by neuropathy, so it's difficult to re-treat patients when their disease recurs. Drugs such as trabectedin, which are active yet don't appear to cause neuropathy, could have interesting applications," he said. "The hope moving forward is that we will be able to combine trabectedin with other agents."

Chemotherapy Foundation Symposium XXIV. Presented November 9, 2006.