阶段我和药代动力学试验AP5346, DACH-platinum-polymer共轭,每4周每周进行三晚期实体瘤患者。

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Campone M, Rademaker-Lakhai JM, Bennouna J,豪厄尔某人,Nowotnik DP, Beijnen JH, Schellens JH

阶段我和药代动力学试验AP5346, DACH-platinum-polymer共轭,每4周每周进行三晚期实体瘤患者。

癌症Chemother杂志。2007年9月,60(4):523 - 33所示。Epub 2007年2月17日。

PubMed ID

17308894 (在PubMed

]

文摘

目的:确定最大耐受剂量(MTD)的安全性和药物动力学AP5346, copolymer-linked 1, 2-diaminocyclohexane(达奇)铂化合物,在晚期实体瘤患者。实验设计:AP5346还小时静脉输液1天,8 15 28天的周期。七个剂量水平(DL)进行了探讨:DL1: 40毫克铂(Pt) / m2(1例);DL2: 80 (1);DL3: 160 (3);DL4: 320 (3);DL5: 640 (6);DL6: 850 (6);DL7: 1280(6)毫克Pt / m2。Dose-limiting毒性(DLT)包括注入遗漏和周期延迟> 2周。 RESULTS: Twenty-six patients received 41 cycles (median 1/patient, range 1-4). No DLT occurred in DL 1-4; 1 DLT in DL5 (RD; renal insufficiency), two in DL6 (MTD; vomiting; fatigue) and 5 in DL7 (neutropenic infection with diarrhea; neutropenia with vomiting; vomiting with fatigue; renal insufficiency; and fatigue). Two deaths occurred due to renal insufficiency (DL5); in both cases patients had disease in or surrounding genitourinary tract whose contribution could not be accurately discerned. Grade 1-2 creatinine abnormalities occurred in seven patients. Nausea/emesis was frequent (92%), reaching grade 3-4 (23%), but controlled by antiemetics. Grade 2-4 allergic reactions occurred in 4 patients. Cmax and AUC increased linearly with dose for total plasma platinum and ultrafiltrate platinum. Antitumor activity included two partial responses in metastatic melanoma and ovarian cancer, and an additional CA-125 normalization (from 133 IU/l) in a suspected ovarian cancer. CONCLUSIONS: AP5346 administered weekly for 3 weeks out of every four is tolerated up to a dose of 640 mg Pt/m2 on the first cycle when given with antiemetic prophylaxis. The pharmacokinetics of AP5346 indicates a prolonged half-life, and evidence of antitumor activity was observed at this dose level.

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药物

AP5346