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Phase I Trial of Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) with Cisplatin, Mitomycin, and Paclitaxel in Patients with Gastric Adenocarcinoma and Associated Carcinomatosis or Positive Cytology.
胃腺癌伴相关癌病或细胞学阳性患者腹腔热灌注化疗 (HIPEC) 联合顺铂、丝裂霉素和紫杉醇的 I 期试验。
- 影响因子：3.60
- DOI：10.1245/s10434-020-08226-x
- 作者列表："Blum Murphy M","Ikoma N","Wang X","Estrella J","Roy-Chowdhuri S","Das P","Minsky BD","Song S","Mansfield P","Ajani J","Badgwell B
- 发表时间：2020-01-23
Abstract
BACKGROUND:The purpose of this phase I trial is to evaluate the safety and toxicity of laparoscopic hyperthermic intraperitoneal perfusion with chemotherapy (HIPEC), combining mitomycin, cisplatin, and paclitaxel for patients with gastric cancer metastatic to the peritoneum. PATIENTS AND METHODS:A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of paclitaxel in combination with flat doses of mitomycin (30 mg) and cisplatin (200 mg) during laparoscopic HIPEC. The primary objective is to define the maximum tolerated dose. Secondary endpoints include surgical complications and overall survival (OS). RESULTS:A total of 27 patients were treated between 11/2017 and 11/2018. No dose-limiting toxicities were observed. Treatment-related grade 1-2 toxicities were leukopenia (11%), oral dysesthesia (4%), arthralgia (4%), and diarrhea (4%). Treatment-related grade 3-4 toxicities included leukopenia (4%) and neutropenia (4%). The maximum dose for paclitaxel was 60 mg/m2. Rates of Clavien-Dindo surgical complications were grade I 96% (all electrolyte deficiencies requiring replacement), II 4%, III 0%, IV 0%, and V 4%. The median follow-up time was 15 months. One- and 2-year OS rates from date of metastatic disease were 73.9% and 58.1%, respectively. CONCLUSIONS:Laparoscopic HIPEC with mitomycin, cisplatin, and paclitaxel may be safely used at intraperitoneal doses of 30 mg, 200 mg, and 60 mg/m2, respectively. Although electrolyte abnormalities were common, systemic toxicity was low. Survival rates were promising, supporting further research into intraperitoneal therapy for stage IV gastric cancer.
摘要
背景: 本 I 期试验的目的是评估腹腔镜腹腔热灌注化疗 (HIPEC) 联合丝裂霉素、顺铂、和紫杉醇用于胃癌转移至腹膜的患者。 患者和方法: 采用贝叶斯最佳间隔设计，前瞻性地确定递增剂量的紫杉醇联合丝裂霉素 (30 mg) 和顺铂 (200 mg) 的安全性和耐受性腹腔镜 HIPEC 期间。主要目标是定义最大耐受剂量。次要终点包括手术并发症和总生存期 (OS)。 结果: 共有 27 例患者接受了 11/2017 至 11/2018 的治疗。未观察到剂量限制性毒性。治疗相关的 1-2 级毒性反应为白细胞减少 (11%)，口腔感觉迟钝 (4)，关节痛 (4%) 和腹泻 (4%)。治疗相关的 3-4 级毒性反应包括白细胞减少 (4%) 和中性粒细胞减少 (4%)。紫杉醇的最大剂量为 60 mg/m2。Clavien-Dindo 手术并发症发生率为 I 级 96% (所有电解质缺乏需要更换) 、 II 级 4% 、 III 级 0% 、 IV 级 0% 和 V 级 4%。中位随访时间为 15 个月。从转移性疾病发生之日起，1 年和 2 年 OS 率分别为 73.9% 和 58.1%。 结论: 腹腔镜 HIPEC 联合丝裂霉素、顺铂和紫杉醇可安全使用，腹腔剂量分别为 30 mg 、 200 mg 和 60 mg/m2。尽管电解质异常很常见，但全身毒性较低。生存率是有希望的，支持进一步研究 IV 期胃癌的腹腔内治疗。
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