HIPEC with oxaliplatin in the treatment of peritoneal carcinomatosis of colorectal origin

Abstract

Cisplatin is one of the most frequently used antineoplastic agents in association with hyperthermic intraperitoneal chemoperfusion (HIPEC) [1-4]. The rationale for its use is its potentiation at high temperatures and its ability to act at any stage of malignant cell replication [1]. However, while this drug has a proven activity in the treatment of intraperitoneal malignancies such as gastric and ovarian carcinoma [5-7], no such efficacy has been demonstrated in colorectal or appendiceal adenocarcinoma. Oxaliplatin (LOHP) is a third generation platinum complex with a diaminocyclohexane carrier group, and an oxalate leaving ligand. It induces no renal or hepatic toxicity, but may cause cumulative sensory neuropathy, thus limiting the total dose to be delivered. It yields high response rates and improves survival in patients with metastatic colorectal cancer. The objective response rate was 24% when administered as a single agent in second-line intravenous chemotherapy, and around 55% when given upfront combined with 5-FU and leucovorin at a dose intensity of 40-50 mg/m/week [8-10]. Recently, cytoreduction followed by HIPEC has been introduced in the management of peritoneal carcinomatosis (PC) [5,11-13]. Cytoreduction should be as complete as possible since experimental studies have shown that drug penetration is limited to a few cell layers under the tumour surface [14]. Intraperitoneal chemotherapy must be immediate, thus avoiding the trapping of residual tumour cells in postoperative fibrin adhesions [15,16]. HIPEC ensures a high local concentration of antineoplastic agents [1], and their cytotoxicity is improved by hyperthermia [1] while that of LOHP is increased by 180% [17]. LOHP should be a more interesting agent for HIPEC in colorectal carcinomatosis than the drugs currently used: mainly mitomycin [1,2,4-6], which has a limited efficacy against such tumours, and 5-FU, a long-acting drug which is not potentiated by hyperthermia (18). In this chapter, we report the results of consecutive prospective trials of HIPEC with LOHP following complete cytoreductive surgery for colorectal PC.