PIPAC for peritoneal metastases of colorectal cancer

Background of study

Approximately a quarter of the patients who are diagnosed with colorectal cancer and metastases have their metastases in the peritoneum, the so called peritoneal metastases. The vast majority of these patients cannot be cured by surgery, frequently due to too many peritoneal metastases. These inoperable patients have a very short life expectancy. Nowadays, they are treated with chemotherapy through the veins. However, chemotherapy through the veins seems to be relatively ineffective against peritoneal metastases, probably because it does not reach the peritoneal metastases very well. Chemotherapy through the veins may also cause side effects that are sometimes severe. Recently, doctors developed PIPAC: a short laparoscopic operation during which chemotherapy is sprayed in the abdomen for 30 minutes every four to six weeks, directly against the peritoneal metastases. As a result, PIPAC may as effective against peritoneal metastases than chemotherapy through the veins, but it may cause less side effects because the chemotherapy stays in the abdomen. Although PIPAC indeed shows promising results in the first patients, little is still known about its safety, feasibility, tolerability, and efficacy.



Aim of study

To investigate whether PIPAC is a safe, feasible, tolerable, and potentially effective treatment for patients with inoperable peritoneal metastases of colorectal cancer.



Participants

Patients with inoperable peritoneal metastases of colorectal cancer without metastases elsewhere (e.g. liver, lung)



Treatment

Instead of chemotherapy through the veins, participants receive PIPAC every 6 weeks. PIPAC is a laparoscopic operation under general anaesthesia. During PIPAC, chemotherapy is sprayed in the abdomen for about 30 minutes. After PIPAC, patients stay in the hospital for one night. Four weeks after each PIPAC, patients visit the hospital for a scan and to evaluate whether PIPAC can be continued. PIPAC is continued until (1) the cancer grows, (2) PIPAC causes unacceptable side effects, or (3) PIPAC is technically not possible to perform. In case no further PIPAC is performed, restarting chemotherapy through the veins is discussed with the patient.



Potential risks for participants

PIPAC may cause side-effects. The most frequent potential side-effects are pain, nausea, fever, wound infection, diarrhea, obstipation, and minor damages to the kidney, liver, and bone marrow. These side-effects are mostly very mild. Moreover, the risk of side-effects of PIPAC is thought to be lower than the risk of side-effects of chemotherapy through the veins. Severe side-effects of PIPAC are extremely rare. The most important are a bowel perforation or a bleeding during PIPAC. So far, these severe side-effects have not been observed during PIPAC in patients with peritoneal metastases of colorectal cancer.



Potential benefits for participants

PIPAC may potentially be similarly effective against peritoneal metastases than chemotherapy through the veins, with a potential lower risk of side-effects. However, these potential benefits remain uncertain. The cancer may deteriorate at any moment during treatment with PIPAC.



Hypothesis of study

The investigators expect that PIPAC is a safe, feasible, tolerable, and potentially effective treatment for patients with peritoneal metastases of colorectal cancer.

Repetitive ePIPAC-OX as a palliative monotherapy is a feasible, safe, tolerable, and potentially effective treatment for isolated unresectable colorectal peritioneal metastases, with low and predictable costs and a low systemic uptake of oxaliplatin.

See sections 'Primary outcome(s)' and 'secondary outcome(s)' above

Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2 body-surface area [BSA]) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four weeks after each procedure, patients undergo clinical, radiological, and biochemical evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease progression, after which standard palliative treatment is (re)considered.