Phase 2: a dose-escalation study of OncoGel (ReGel/paclitaxel), a controlled-release formulation of paclitaxel, as adjunctive local therapy to external-beam radiation in patients with inoperable esophageal cancer
Phase 2: a dose-escalation study of OncoGel (ReGel/paclitaxel), a controlled-release formulation of paclitaxel, as adjunctive local therapy to external-beam radiation in patients with inoperable esophageal cancer
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DOI：
10.1097/cad.0b013e3283222c12
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发表时间：
2009-02-01
影响因子：
2.3
通讯作者：
Fowers, Kirk D.
中科院分区：
文献类型：
--
作者：
DuValla, G. Aaron;Tarabar, Dino;Fowers, Kirk D.
OncoGel是一种生物相容性生物可降解凝胶（ReGel）中紫杉醇的新型注射制剂，可在注射部位控制紫杉醇的释放，导致高病灶内紫杉醇浓度和持续的放射增敏作用，而不会伴随全身毒性。这项剂量递增研究评价了在无法手术的食管癌患者中病灶内注射OncoGel的毒性、药代动力学和初步抗肿瘤活性，这些患者是姑息性外束放疗（RT）的候选人。11例无法手术的晚期食管癌患者接受了使用传统内镜技术对原发性肿瘤进行单次OncoGel给药。三个队列接受约三分之一的肿瘤体积，增加紫杉醇浓度，以达到0.48、1.0和2.0 mg紫杉醇/cm（3）肿瘤体积。注射后，开始RT（50.4戈伊，分1.8戈伊）。进行药代动力学采样。所有患者均完成研究。未报告剂量限制性毒性。大多数患者吞咽困难改善，肿瘤尺寸缩小。11例患者中有4例活检为阴性。紫杉醇血浆峰浓度较低（0.53-2.73 ng/ml），与紫杉醇给药的绝对量直接相关。所有患者血浆中的紫杉醇可检测24小时，6例患者可检测3周。OncoGel作为RT的辅助治疗在不能手术的食管癌患者中耐受性良好，并在全身暴露最小的情况下延长紫杉醇释放。OncoGel + RT似乎可降低肿瘤负荷，如吞咽困难改善、肿瘤大小减小和食管活检阴性所证明。将OncoGel添加到联合治疗中值得继续进行临床开发。抗癌药物20：89-95（C）2009年沃尔特斯Kluwer健康垂直酒吧Lippincott威廉姆斯&威尔金斯。
OncoGel, a novel injectable formulation of paclitaxel in a biocompatible biodegradable gel (ReGel), provides controlled release of paclitaxel at the Injection site, resulting in high intralesional paclitaxel concentrations and continuous radiosensitization without attendant systemic toxicities. This dose-escalation study evaluated the toxicity, pharmacokinetics, and preliminary antitumor activity of OncoGel injected intralesionally in patients with inoperable esophageal cancer who were candidates for palliative external-beam radiotherapy (RT). Eleven patients with inoperable advanced esophageal cancer received a single administration of OncoGel into the primary tumor using conventional endoscopic techniques. Three cohorts received approximately one-third of the tumor volume with increasing paclitaxel concentrations to achieve 0.48, 1.0, and 2.0 mg paclitaxel/cm(3) tumor volume. Subsequent to injection, RT was initiated (50.4 Gy in 1.8 Gy fractions). Pharmacokinetic sampling was performed. All patients completed the study. No dose-limiting toxicities were reported. Dysphagia Improved and tumor size decreased in most patients. Biopsies were negative for carcinoma in 4 of 11 patients. Peak paclitaxel plasma concentrations were low (0.53-2.73 ng/ml) and directly related to the absolute amount of paclitaxel administered. Paclitaxel was detectable in plasma for 24 h in all patients and for 3 weeks in six patients. OncoGel given as an adjunct to RT was well tolerated in patients with inoperable esophageal cancer and provided prolonged paclitaxel release with minimal systemic exposure. OncoGel plus RT seemed to reduce tumor burden as evidenced by dysphagia improvement tumor size reduction, and negative esophageal biopsies. The addition of OncoGel to combined modality therapy merits continued clinical development. Anti-Cancer Drugs 20:89-95 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.