The Role of Systemic Chemotherapy

Abstract

Development of peritoneal carcinomatosis (PC) in metastatic solid tumors is associated with poor prognosis and is usually more frequent in gynecological and gastrointestinal (GI) malignancies. No standard systemic or local treatment can eradicate PC definitively, and chemotherapy (CHT) and surgery alone seem unable to improve patient survival, so that PC is usually considered a terminal condition [1]. PC is commonly observed in ovarian cancer (OC), in which the spread of disease is primarily locoregional and then to visceral sites. In this pathology, complete PC removal is associated with improved survival. In GI tumors, such as gastric and colorectal cancer (CRC), PC is seen less frequently, and its cytoreduction is not considered mandatory due to the high percentage of short-term recurrence and no effect on survival rates [2]. Systemic CHT has a limited impact on the peritoneum, probably because the peritoneal cavity is a “pharmacological sanctuary” in which intravenously administered drug diffusion is difficult. This is due to a blood-peritoneal barrier, composed of stromal tissues between mesothelial and endothelial cells, of ∼90-μm thickness, which is difficult to overcome by many systemic agents [3]. Given this low effectiveness of systemic therapies or surgery alone and the necessity to improve the local action of drugs, in recent decades, new multimodal approaches have been developed based on the association of cytoreductive surgery (CRS) with intravenous (IV) (neoadjuvant or adjuvant) and/or intraperitoneal (IP) administration of CHT (IP-CHT). Different combinations and integrations of these treatments have been proposed and evaluated in randomized or nonrandomized trials in many cancer types.