The Effectiveness of Cytoreductive Surgery with Intraperitoneal Hyperthermic Chemotherapy(IPHC) for Far-Advanced Gastric Cancer

Noh, Sung Hoon; Kim, Yong Il; Yoo, Chang Hak; Yoo, Nae Choon; Chung, Hyun Cheol; Min, Jin Sik

Abstract

A prominent cause of death in patients with advanced gastric cancer is peritoneal metastasis or recurrence. There is no definite preventive surgery or treatment in such cases. Cancer tissue is more heat labile than normal tissue, and the administration of anticancer drugs interacts synergically with hyperthermia. The ability of anticancer drugs to eradicate the malignant cells is dependent not only on the dose of the antineoplastic drug but also on the number of tumor cells. Therefore, for success, the combination therapy of cytoreductive surgery and IPHC may be necessary in advanced gastric cancer. We performed this study to evaluate the toxicity and the clinical efficacy of IPHC in far-advanced gastric cancer and to assess the concentration of CDDP. Twenty one patients (11 females and 10 males) with gross serosal invasion (with or without peritoneal metastasis) underwent cytoreductive surgery and were treated with IPHC via hyperex-GHT-cpl (Green Cross Med. Corp. Korea) before closure of the abdominal wound. The IPHC was done using CDDP (200~400 mg/m2) and MMC (30~50 mg/m2) with 10 liters of normal saline as the perfusate. The peritoneal temperature during the IPHC was maintained at 42oC for 60 minutes. We used a modified peritoneal cavity expander to achieve free flow of the perfusate. The concentrations of the plasma and the perfusate were measured by atomic absorption spectrometry (Varian 300 A). Sixteen patients were stage IV, 3 were IIIb, and 2 were IIIa. The plasma concentraton of CDDP was 1.8 ug/ml at 10 minutes after perfusion and reached a maximal concentration (MXC) of 3.6 ug/ml. The area under the time-concentration curve (AUC) of the plasma at the 48th hour after perfusion was 3031.1 ug.min/ml. At the 24th hour, the maximum concentration of CDDP in the perfusate was 16.2 ug/ml. The AUC of the perfusate was 1703.3 ug min/ml at the 24th hour and 1817.7 ug min/ml at the 48th hour. The ratio of AUC of perfusate and the AUC of the plasma were 0.92 at the 24th hour and 0.59 at the 48th hour. The postoperative compllications were lymphatic leakage (2), pneumonia (1), and paralytic ileus (1). The most common drug-related complications of IPHC were anemia (WHO grade I), hematuria, leukopenia, jaundice, and thrombocytopenia in such order. These side effects were eliminated by conservative treatment within 4 weeks postoperatively. We could not determine the long term survival rate because of the short follow up period. However, the mean survival of the cases was about 12.0 months. The three deaths among the resected cases were due to extraperitoneal recurrences. The combination therapy of IPHC and cytoreductive is available for clinical use with a high AUC, high intraperitoneal CDDP concentration with a reasonable plasma concentration and has no threatening complications or mortality.