D Elias, M Pocard, D Goere

Peritoneal Carcinomatosis: A Multidisciplinary Approach (2007)
Peritoneal carcinomatosis is a term that describes the spread of tumor on the peritoneum ( the inner lining of the abdomen and pelvic areas. In PMP, the spread is usually from a ruptured cancerous cyst which forms on the appendix. Patients with PMP used to be considered incurable, but now cytoreduction surgery (CRS) coupled with hyperthermic Intraperitoneal chemotherapy(HIPEC) are used to treat PMP and various peritoneal cancers with good results. The aim of cytoreduction is to ensure complete removal of macroscopic cancerous tumors (visible tumor larger than 2.5mm) in the affected areas. Generally the procedure involves removing the spleen, the omentum (covering of the abdomen), appendix, gall bladder, parts or the whole colon, and parts of cancerous rectum. In women, a hysterectomy and salpingoo-ophorectomy (removal of the ovaries)is also performed. Cytoreduction is then followed by administering HIPEC.

The administration of HIPEC must be immediate so as to avoid the entrapment of tumor cells in scar tissue that forms as the body heals from surgery. It should also be administered at temperatures higher than body temperature to render it potent against microscopic tumor cells. In this article, the results of consecutive trials of HIPEC using oxaliplatin (LOHP)are reported following complete cytoreduction surgery for colorectal peritoneal carcinomatosis.

Twenty three patients with PC had complete cytoreduction surgery which was followed by intraoperative HIPEC (Open method) with increased dosing of oxaliplatin(260mg/m2- 460mg/m2). One hour before HIPEC patients received systemic IV leucovorin 20mg/m2 to increase the potency of LOHP. The duration of HIPEC lasted for 30minutes and was given at a temperature greater than 42 degrees. The average duration of the entire procedure was about 8.4hrs. AUC (area under curve) values and maximal plasma concentration(C max) increased with each dose.

The AUC values are used to determine how the drug is absorbed into peritoneum, tumor tissue, and the blood stream. It also measures the time it takes the drugs to clear out of the body. It was found that at the highest dose level peritoneal oxaliplatin concentration was 25 times that of plasma concentration. Intratumor LOHP penetration was 17.8-fold higher than that in unbathed tissue. At the same time, concentration of the drug in the blood stream was consistently below control AUCs after IV LOHP. They were no deaths, hemorrhaging, kidney malfunction or brain malfunction, although two fistulas (perforations) and 3 abscesses were observed.

In conclusion, heated intraperitoneal chemotherapy gives high peritoneal and tumor oxaliplatin concentrations with limited systemic absorption. The authors recommended an oxaliplatin dose of 460 mg/m2 in 2 l/m2 of 5% dextrose for intraperitoneal chemo-hyperthermia, at a temperature of 42-44[degrees]C over 30 min. Improvement of these results may be possible by increasing the intraperitoneal perfusion duration or by modifying the instillate composition.