Yovine A, Riofrio M, Blay J Y, Brain E, Alexandre J, Kahatt C, Taamma A, Jimeno J, Martin C, Salhi Y, Cvitkovic E, Misset J L
Hôpital St Louis, Unité d'Oncologie Médicale, 1 av. Claude Vellefaux, 75010 Paris, France.
J Clin Oncol. 2004 Mar 1;22(5):890-9. doi: 10.1200/JCO.2004.05.210.
A multicenter phase II study evaluating efficacy, safety, and pharmacokinetics of ecteinascidin-743 (ET-743) in pretreated advanced soft tissue sarcoma patients.
Patients received ET-743 1,500 microg/m(2) (24-hour intravenous infusion) every 3 weeks (group 1, 26 patients with one to two prior single agents or one previous combination chemotherapy; group 2, 28 patients with three or more prior single agents or two or more previous combination chemotherapies). Results Patients (30 women, 24 men) had a median age of 48 years (range, 22 to 71 years); 41% had leiomyosarcoma (eight of 22 of uterine origin), a median of two involved organs (range, one to four), and 93% had documented progressive disease at study entry. Patients received a median of three cycles (range, one to 20); 28% received six or more cycles. Fifty-two patients were assessable for response (WHO criteria): two partial responses, four minor responses, and nine with stable disease (> or = 6 months). Three patients were rendered tumor free after surgery. Median progression-free survival was 1.9 months (range, 0.69 to 17.90 months); 24% of patients were progression free at 6 months. Median survival was 12.8 months, with 30% of patients alive at 2 years. Four patients withdrew because of treatment-related toxicity. Two treatment-related deaths occurred (renal failure and febrile neutropenia, and rhabdomyolysis and decompensated cirrhosis, respectively) that were probably related to protocol eligibility violations. Reversible grade 3 to 4 AST or ALT occurred in 50% of patients and grade 3 to 4 neutropenia occurred in 61% of patients, with six episodes of febrile neutropenia. Nausea, vomiting, and asthenia were prevalent but mild and manageable.
With a 4% overall response rate (95% CI, 0.5 to 12.8) and an 11% rate of third-party-verified tumor regression (overall response rate + minor response), ET-743 has a 24% 6-month disease progression control rate, confirming evidence of antitumoral activity and a manageable safety profile in patients experiencing disease progression with pretreated soft tissue sarcoma.
一项多中心II期研究，评估埃博霉素-743（ET-743）在经预处理的晚期软组织肉瘤患者中的疗效、安全性和药代动力学。
患者每3周接受1500微克/平方米的ET-743（24小时静脉输注）（第1组，26例曾接受过一至两种单药或一种联合化疗的患者；第2组，28例曾接受过三种或更多单药或两种或更多联合化疗的患者）。结果患者（30名女性，24名男性）的中位年龄为48岁（范围22至71岁）；41%患有平滑肌肉瘤（22例中有8例起源于子宫），中位累及器官数为2个（范围1至4个），93%在研究入组时记录有疾病进展。患者接受的中位周期数为3个（范围1至20个）；28%接受了6个或更多周期。52例患者可评估疗效（按照世界卫生组织标准）：2例部分缓解，4例轻度缓解，9例病情稳定（≥6个月）。3例患者术后肿瘤消失。中位无进展生存期为1.9个月（范围0.69至17.90个月）；24%的患者在6个月时无疾病进展。中位生存期为12.8个月，30%的患者在2年时存活。4例患者因治疗相关毒性退出。发生了2例与治疗相关的死亡（分别为肾衰竭和发热性中性粒细胞减少症，以及横纹肌溶解和失代偿性肝硬化），可能与违反方案入选标准有关。50%的患者出现可逆性3至4级谷草转氨酶或谷丙转氨酶升高，61%的患者出现3至4级中性粒细胞减少症，有6次发热性中性粒细胞减少症发作。恶心、呕吐和乏力很常见，但程度较轻且可控制。
ET-743的总缓解率为4%（95%置信区间，0.5至12.8），经第三方验证的肿瘤退缩率为11%（总缓解率+轻度缓解），6个月疾病进展控制率为24%，证实了其在疾病进展的经预处理软组织肉瘤患者中的抗肿瘤活性及可控的安全性。
