Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Chemother Pharmacol. 2018 Nov;82(5):877-885. doi: 10.1007/s00280-018-3680-y. Epub 2018 Sep 4.
We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/- bevacizumab in advanced cancer with predominant liver involvement.
Patients received HAI oxaliplatin (140 mg/m) and escalating doses of capecitabine (500, 750, and 1000 mg/m), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase.
From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20-88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1-12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m, capecitabine 750 mg/m, and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2).
HAI oxaliplatin combined with capecitabine +/- bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.
我们研究了肝动脉灌注（HAI）奥沙利铂联合卡培他滨（±贝伐珠单抗）治疗以肝转移为主的晚期癌症。
患者接受 HAI 奥沙利铂（140mg/m）和递增剂量的卡培他滨（500、750 和 1000mg/m），联合（第 1 组）或不联合（第 2 组）贝伐珠单抗（10mg/kg IV）。采用 3+3 剂量设计，随后进行扩展阶段。
2009 年 9 月至 2014 年 2 月，共纳入 61 例患者（34 例男性，27 例女性）（第 1 组 44 例，第 2 组 17 例）。如果患者有贝伐珠单抗的禁忌证（n=13）或第 1 组无空位（n=4），则将其纳入第 2 组治疗。中位年龄为 60 岁（范围，20-88 岁）。最常见的癌症是结直肠癌（22 例）、肝癌（12 例）、胰腺癌（7 例）、乳腺癌（4 例）和胆道癌（4 例）。中位治疗前方案数为 3（范围，1-12）；32 例（53%）患者接受过奥沙利铂治疗。剂量限制毒性为 3 级腹泻，发生在 2 例接受 1000mg/m 卡培他滨的患者中。最大耐受剂量为 HAI 奥沙利铂 140mg/m、卡培他滨 750mg/m 和贝伐珠单抗 10mg/kg。最常见的毒性是恶心/呕吐、贫血、血小板减少、中性粒细胞减少和低镁血症。部分缓解和疾病稳定≥4 个月的比例分别为 22%和 39%（第 1 组）和 9%和 0%（第 2 组）。相应的中位治疗失败时间和总生存期分别为 3 个月和 6.9 个月（第 1 组）和 1.5 个月和 5.9 个月（第 2 组）。
HAI 奥沙利铂联合卡培他滨（±贝伐珠单抗）在选择的患者中耐受性良好，且治疗结局良好。
