A phase I study of rebeccamycin analog in combination with oxaliplatin in patients with refractory solid tumors.
A phase I study of rebeccamycin analog in combination with oxaliplatin in patients with refractory solid tumors.
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DOI：
10.1007/s10637-009-9322-9
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发表时间：
2011-02
影响因子：
3.4
通讯作者：
Dowlati, Afshin
中科院分区：
文献类型：
--
作者：
Nock, Charles J.;Brell, Joanna M.;Bokar, Joseph A.;Cooney, Matthew M.;Cooper, Brenda;Gibbons, Joseph;Krishnamurthi, Smitha;Manda, Sudhir;Savvides, Panayiotis;Remick, Scot C.;Ivy, Percy;Dowlati, Afshin
红霉素类似物（RA）是一种具有拓扑异构酶I和拓扑异构酶II抑制活性的抗肿瘤抗生素。拓扑异构酶抑制剂已证明与铂剂的协同作用。我们在难治性实体瘤患者中进行了RA联合奥沙利铂的I期试验。在第1-5天，每天1小时输注RA，第5天给予奥沙利铂。每21天重复一个周期。共入组17例患者。RA的MTD为80 mg/m2/d，持续5天沿着奥沙利铂为130 mg/m2，第5天。骨髓抑制是常见事件，但除1例外均为轻度。剂量限制性毒性包括房颤和低磷血症。有抗肿瘤活性的证据，包括3例食管癌、胆囊癌和肝细胞癌患者的部分缓解;另外5例患者病情稳定。因此，RA和奥沙利铂的联合治疗是可耐受的，并且具有临床活性的证据，但鉴于RA单药在各种疾病部位缺乏显著活性，因此不太可能进行II期开发。
Rebeccamycin analog (RA) is an antitumor antibiotic with both topoisomerase I and II inhibiting activity. Topoisomerase inhibitors have demonstrated synergy with platinum agents. We performed a phase I trial of combination RA with oxaliplatin in patients with refractory solid tumors. RA was administered as a 1-hour infusion daily on days 1–5 with oxaliplatin administered on day 5. Cycles were repeated every 21 days. A total of 17 patients were enrolled. The MTD for RA was 80 mg/m2/d for five days along with oxaliplatin 130 mg/m2 on day 5. Myelosuppression was a common occurrence but was mild except in one instance. Dose limiting toxicities included atrial fibrillation and hypophosphatemia. There was evidence of antitumor activity including 3 partial responses in patients with esophageal, gallbladder and hepato-cellular carcinoma; 5 additional patients had stable disease. Thus, the combination of RA and oxaliplatin is both tolerable and has evidence of clinical activity, but given the lack of significant activity for single agent RA across a variety of disease sites, it is unlikely to proceed to phase II development.
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影响因子：
8.4
作者：
Gross-Goupil, M;Lokiec, F;Goldwasser, F
通讯作者：
Goldwasser, F
影响因子：
6.2
作者：
McGregor, Lisa M.;Spunt, Sheri L.;Fouladi, Maryam
通讯作者：
Fouladi, Maryam
影响因子：
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作者：
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影响因子：
3.3
作者：
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影响因子：
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作者：
Ricart, AD;Hammond, LA;Rowinsky, EK
通讯作者：
Rowinsky, EK