Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial
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Peritoneal 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.
Colorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20 mg/m2 of ip PTX was administered weekly, in combination with mFOLFOX6-bevacizumab or CapeOX-bevacizumab. Primary endpoint was the safety of the combination chemotherapy.
Among 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.
The 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.
KeywordsPhase I trial Intraperitoneal paclitaxel Colorectal cancer Peritoneal carcinomatosis
This research is supported by Grants-in-Aid for Scientific Research (C: Grant number; 16K07143, C: Grant number; 16K07161, C: Grant number; 17K10620, C: Grant number; 17K10621, C: Grant number; 17K10623 and C: Grant number; 18K07194) from Japan Society for the promotion of Science. This research is supported by the Project for Cancer Research and Therapeutic Evolution (P-CREATE, grant number: 18 cm0106502h0003 from the Japan Agency for Medical Research and Development (AMED).
Compliance with ethical standards
Conflict of interest
K. Muro is on the advisory board meeting for Bristol-Myers Squibb and Nippon Kayaku Co, Ltd. All remaining authors have declared no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee of the University of Tokyo (P2015038-11X) and with the 1964 Helsinki declaration and its later amendments. The study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) (UNIN000022924).
Written informed consent was obtained from all individual participants included in the study.
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