Conversion to Resectability Using Hepatic Artery Infusion Plus Systemic Chemotherapy for the Treatment of Unresectable Liver Metastases From Colorectal Carcinoma

Abstract

PURPOSE To determine the conversion to resectability in patients with unresectable liver metastases from colorectal cancer treated with hepatic arterial infusion (HAI) plus systemic oxaliplatin and irinotecan (CPT-11). PATIENTS AND METHODS Forty-nine patients with unresectable liver metastases (53% previously treated with chemotherapy) were enrolled onto a phase I protocol with HAI floxuridine and dexamethasone plus systemic chemotherapy with oxaliplatin and irinotecan. Results Ninety-two percent of the 49 patients had complete (8%) or partial (84%) response, and 23 (47%) of the 49 patients were able to undergo resection in a group of patients with extensive disease (73% with > five liver lesions, 98% with bilobar disease, 86% with > or = six segments involved). For chemotherapy-naïve and previously treated patients, the median survival from the start of HAI therapy was 50.8 and 35 months, respectively. The only baseline variable significantly associated with a higher resection rate was female sex. Variables reflecting extensive anatomic disease, such as number of lesions or number of vessels involved, were not significantly associated with the probability of resection. CONCLUSION The combination of regional HAI floxuridine/dexamethasone and systemic oxaliplatin and irinotecan is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, demonstrating a 47% conversion to resection (57% in chemotherapy-naïve patients). Future randomized trials should compare HAI plus systemic chemotherapy with systemic therapy alone to assess the additional value of HAI therapy in converting patients with hepatic metastases to resectability.

The preliminary experience in simultaneous treatment of rectal cancer and synchronous liver metastases with laparoscopy

“…HAI of chemotherapy has been used in patients with unresectable metastases confined to the liver. Kemeny et al (25) found that the combination of regional HAI floxuridine/dexamethasone and systemic oxaliplatin and irinotecan is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, demonstrating a 47% conversion to resection. With laparoscopy, we successfully implanted a chemotherapy pump into the hepatic artery; meanwhile, the main lesions of the liver were administrated ethanol to induce tumor necrosis and reduce tumor burden.…”

“…Therefore, the liver lesions resulted in fatality after the primary tumor was resected. For these patients, hepatic artery infusion (HAI) was often suggested to provide for the lesions in the liver (25). HAI of chemotherapy has been used in patients with unresectable metastases confined to the liver.…”

“…HAI is vital to prolong the survival of patients due to less chemotherapy systemic effects and higher local drug concentration (4). Massive tumor reduction may guarantee a better response to adjuvant chemotherapy, and the absence of repeated postoperative immunodeficiency improves patient immunological defense against tumor cells (4,25,26) and the quality of life, prolonging the survival time.…”

Preoperative intraperitoneal oxaliplatin for unresectable peritoneal carcinomatosis of colorectal origin: a pilot study

“…A French group has demonstrated the prognostic similarities of PC and liver metastases in colorectal cancer when there was only one metastatic site involved [26]. Bilateral suboptimally resectable liver metastases are initially treated with hepatic intra-arterial infusion (HAIP) associated with systemic chemotherapy which offers conversion to resectability in 25-50 % of all cases [38,39]. A similar strategy in the initially unresectable PC of colorectal origin may correspond to the present protocol.…”

“…The demographic, clinical and histological characteristics of the patients are shown in Table 1. The median PCI was 29.5 (range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. One patient developed a recurrence of already treated PC associated with a midline parietal metastasis.…”