Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial
Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial
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DOI：
10.1007/s00280-018-3714-5
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发表时间：
2019-01-01
影响因子：
3
通讯作者：
Ishihara, Soichiro
中科院分区：
文献类型：
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作者：
Murono, Koji;Nagata, Hiroshi;Ishihara, Soichiro
结直肠癌腹膜转移与预后不良有关。关于卵巢癌、胃癌和胰腺癌，紫杉醇腹腔内给药（ip PTX）的安全性和有效性已得到证实。这种药物可以通过导管容易地反复注入腹膜腔。在这个I期研究中，我们评估了安全性的ip PTX联合5-氟尿嘧啶，亚叶酸，奥沙利铂，贝伐单抗（mFOLFOX 6-贝伐单抗）或卡培他滨，奥沙利铂，贝伐单抗（CapeOX-贝伐单抗）的结直肠癌与腹膜transferation.MethodsColorectal癌组织学证实的腹膜癌转移患者入组。植入腹膜通路后，每周给予20 mg/m2的腹腔注射PTX，联合mFOLFOX 6-贝伐珠单抗或CapeOX-贝伐珠单抗。主要终点是安全性的联合化疗。ResultsAmong 6例患者入组，三个接受mFOLFOX 6-贝伐单抗加ip PTX方案和三个接受CapeOX-贝伐单抗加ip PTX方案。未观察到剂量限制性毒性。总体而言，每种化疗方案的3例患者中有2例（66.7%）观察到3级不良事件，如白细胞减少症和中性粒细胞减少症，但未观察到4级不良事件。此外，不良事件与腹膜接入端口，如感染或堵塞的导管，没有observed.ConclusionsThe不良事件mFOLFOX 6-贝伐单抗或CapeOX-贝伐单抗与ip PTX相结合被认为是类似的奥沙利铂为基础的治疗单独在以前的研究中所描述的。化疗开始后1年，将评价ip PTX的疗效作为次要结局。
PurposePeritoneal carcinomatosis of colorectal cancer origin is associated with poor prognosis. With regard to ovarian, gastric, and pancreatic cancer, the safety and efficacy of intraperitoneal administration of paclitaxel (ip PTX) has been demonstrated. This drug can be administered easily and repeatedly through a catheter into the peritoneal cavity. In this phase I study, we evaluated the safety of ip PTX combined with 5-fluorouracil, folinic acid, oxaliplatin, and bevacizumab (mFOLFOX6-bevacizumab) or capecitabine, oxaliplatin, and bevacizumab (CapeOX-bevacizumab) for colorectal cancer with peritoneal metastasis.MethodsColorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20mg/m(2) of ip PTX was administered weekly, in combination with mFOLFOX6-bevacizumab or CapeOX-bevacizumab. Primary endpoint was the safety of the combination chemotherapy.ResultsAmong the six patients enrolled, three received the mFOLFOX6-bevacizumab plus ip PTX regimen and three received the CapeOX-bevacizumab plus ip PTX regimen. Dose-limiting toxicity was not observed. Overall, grade 3 adverse events, such as leukopenia and neutropenia, were observed in two of three patients (66.7%) for each chemotherapeutic regimen, but no grade 4 adverse events were observed. Moreover, adverse events associated with the peritoneal access port, such as infection or occlusion of the catheter, were not observed.ConclusionsThe adverse events of mFOLFOX6-bevacizumab or CapeOX-bevacizumab in combination with ip PTX were considered similar to those described in previous studies of oxaliplatin-based treatment alone. 1 year after the start of chemotherapy, the efficacy of ip PTX will be evaluated as a secondary outcome.