Phase I Program, Department of Investigational Cancer Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Cancer. 2010 Sep 1;116(17):4086-94. doi: 10.1002/cncr.25277.
Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases.
Treatment consisted of escalating doses of HAI oxaliplatin 60 mg/m(2) to 175 mg/m(2) and intra-arterial heparin 3000 IU (Day 1); leucovorin 200 mg/m(2) intravenously (iv) and 5-fluorouracil 300 mg/m(2) bolus plus 600 mg/m(2) iv (Days 1 and 2); and bevacizumab 10 mg/kg iv (Day 3). A conventional "3 + 3" design was used.
Fifty-seven patients were treated, including 30 women and 27 men. The median age was 57 years, and the patients had received a median of 3 prior therapies (range, 1-7 prior therapies). The most common cancer was colorectal (n = 29). Overall, 204 cycles were administered (median per patient, 2 cycles; range, 1-17 cycles). The maximum tolerated dose (MTD) of HAI oxaliplatin was 140 mg/m(2). Dose-limiting toxicities were grade 4 thrombocytopenia (n = 1) and grade 4 hypokalemia (n = 1) at 150 mg/m(2) (n = 5). Thirty-three patients (58%) had no toxicity greater than grade 1. The most common toxicities were thrombocytopenia (n = 19), fatigue (n = 15), nausea/vomiting (n = 6), constipation (n = 6), and diarrhea (n = 4). Of 55 patients who were evaluable for response (according to Response Evaluation Criteria in Solid Tumors), 4 patients (7%) had a partial response (PR), and 32 patients (58%) had stable disease (SD), including 15 patients (48%) who had SD for >/=4 months. Of 28 patients with colorectal cancer, 3 patients (11%) had a PR, and 9 patients (32%) had SD for >/=4 months.
HAI oxaliplatin combined with systemic 5-fluorouracil, leucovorin, and bevacizumab had antitumor activity in patients with advanced cancer and liver metastases, and the current results indicated that this combination warrants further study. Cancer 2010. (c) 2010 American Cancer Society.
癌症患者的肝转移与预后不良有关。本文作者进行了一项奥沙利铂经肝动脉输注（HAI）联合治疗晚期癌症伴肝转移患者的 1 期研究。
治疗方案为奥沙利铂 HAI 剂量递增，60mg/m(2)至 175mg/m(2)，并经肝动脉内给予肝素 3000IU（第 1 天）；亚叶酸 200mg/m(2)静脉推注（iv）和 5-氟尿嘧啶 300mg/m(2)推注加 600mg/m(2)iv（第 1 和第 2 天）；贝伐单抗 10mg/kg iv（第 3 天）。采用传统的“3+3”设计。
57 例患者接受治疗，其中 30 例为女性，27 例为男性。中位年龄为 57 岁，中位治疗前病史为 3 次（范围 1-7 次）。最常见的癌症为结直肠癌（n=29）。共给予 204 个周期（中位数为每个患者 2 个周期；范围为 1-17 个周期）。奥沙利铂 HAI 的最大耐受剂量（MTD）为 140mg/m(2)。剂量限制毒性为 150mg/m(2)（n=5）时的 4 级血小板减少症（n=1）和 4 级低钾血症（n=1）。33 例（58%）患者无大于 1 级的毒性。最常见的毒性为血小板减少症（n=19）、乏力（n=15）、恶心/呕吐（n=6）、便秘（n=6）和腹泻（n=4）。55 例可评价疗效的患者（根据实体瘤反应评价标准），4 例（7%）患者有部分缓解（PR），32 例（58%）患者疾病稳定（SD），包括 15 例（48%）患者 SD 持续时间大于等于 4 个月。28 例结直肠癌患者中，3 例（11%）患者 PR，9 例（32%）患者 SD 持续时间大于等于 4 个月。
奥沙利铂经肝动脉输注联合全身 5-氟尿嘧啶、亚叶酸和贝伐单抗治疗晚期癌症伴肝转移患者具有抗肿瘤活性，目前的结果表明该联合治疗值得进一步研究。癌症 2010。（c）2010 年美国癌症协会。
