Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial.

Purpose: 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.
Methods: Colorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20 mg/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.
Results: 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.
Conclusions: 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.