Forster Martin, Kaye Stan, Oza Amit, Sklenar Ivo, Johri Anandhi, Cheung Wing, Zaknoen Sara, Gore Martin
Royal Marsden Hospital Gynecology Unit, London, United Kingdom.
Clin Cancer Res. 2007 Jul 15;13(14):4178-84. doi: 10.1158/1078-0432.CCR-06-1653.
Patupilone is a microtubule-targeting chemotherapeutic agent with clinical activity in a broad range of taxane-sensitive/resistant tumor types. The present phase Ib study examined the safety/tolerability and pharmacokinetics of patupilone in combination with carboplatin in patients with advanced solid tumors.
Patients with advanced cancer received patupilone via a 5- to 10-min i.v. infusion at doses of 3.6 to 6.0 mg/m(2) q3w, immediately followed by carboplatin area under the curve (AUC) 5 or 6 mg/mL/min.
Of the 37 patients enrolled, the majority previously received taxanes (81%) and/or platinum-containing drugs (97.3%). The maximum tolerated dose (MTD) of patupilone with carboplatin AUC 6 was 4.8 mg/m(2); additional patients were enrolled to consolidate experience at this dose. Of the 22 patients who received the MTD, the most common nonhematologic adverse events were fatigue in six (27.3%) and diarrhea, nausea, vomiting, abdominal pain, and neuropathy in one each (4.5%; all grade 3); hematologic toxicities included two patients (9.1%) with grade 3 neutropenia. The pharmacokinetics of patupilone were similar to those in a previous study of patupilone monotherapy. Of the 26 patients with recurrent platinum-sensitive ovarian cancer, tumor response was assessable by response evaluation criteria in solid tumors in 17; 1 patient (6%) achieved a complete response, and 10 (59%) achieved a partial response.
The combination of patupilone 4.8 mg/m(2)/carboplatin AUC 6 was well tolerated and showed antitumor activity similar to established regimens in patients with recurrent platinum-sensitive ovarian cancer. The optimal dose for this regimen is currently being further refined in phase II trials.
帕妥珠单抗是一种靶向微管的化疗药物，对多种紫杉烷敏感/耐药的肿瘤类型具有临床活性。本Ib期研究考察了帕妥珠单抗联合卡铂在晚期实体瘤患者中的安全性/耐受性及药代动力学。
晚期癌症患者接受帕妥珠单抗静脉输注5至10分钟，剂量为3.6至6.0mg/m²，每3周一次，随后立即给予卡铂曲线下面积（AUC）为5或6mg/mL/分钟。
37例入组患者中，大多数曾接受过紫杉烷类药物（81%）和/或含铂药物（97.3%）治疗。帕妥珠单抗联合卡铂AUC为6时的最大耐受剂量（MTD）为4.8mg/m²；额外纳入患者以积累该剂量下的经验。在接受MTD的22例患者中，最常见的非血液学不良事件为6例（27.3%）出现疲劳，腹泻、恶心、呕吐、腹痛和神经病变各1例（4.5%；均为3级）；血液学毒性包括2例（9.1%）出现3级中性粒细胞减少。帕妥珠单抗的药代动力学与既往帕妥珠单抗单药治疗研究中的情况相似。在26例复发的铂敏感卵巢癌患者中，17例可根据实体瘤疗效评价标准评估肿瘤反应；1例（6%）达到完全缓解，10例（59%）达到部分缓解。
帕妥珠单抗4.8mg/m²/卡铂AUC为6的联合方案耐受性良好，在复发的铂敏感卵巢癌患者中显示出与既定方案相似的抗肿瘤活性。该方案的最佳剂量目前正在II期试验中进一步优化。
