Regional chemotherapy of non-resectable liver metastases from colorectal cancer - literature and institutional review

Background: Cure is possible by resecting colorectal isolated liver metasta ses. In non-resectable isolated colorectal liver metastases (CRLM). regiona l chemotherapy has been advocated to optimize the disease control in the li ver in order to improve the results of the alternative, systemic chemothera py. The drugs are delivered by means of hepatic artery infusion (HAI) via p orts or pumps; pharmacological modifications of the hepatic arterial blood- flow-like HAI with starch microspheres or stop-flow and perfusion technique s were applied to improve HAI. Methods: We reviewed the literature and repo rt our progress, up to May 1999, in analyzing the validity of HAI for CRLM therapy. Results: In the majority of phase-II and -III trials, the response rates to HAI were significantly higher than those from systemic chemothera py, and local disease control could be achieved even when HAI was used seco nd line to systemic chemotherapy. The meta-analysis of randomized trials co mparing HAI with either systemic chemotherapy (five trials) or, optionally, either 5-fluorouracil (FU) or symptomatic treatment (two trials) showed a significant advantage of HAI in response (41% vs 14%, P<10(-10)) and median survival time(15 months vs 11 months, P<0.0009). The active anabolite of 5 -FU, 5-fluordeoxyuridine (5-FUDR), the drug of choice for HAI in those tria ls, may cause severe hepatotoxicity. To avoid this toxicity, we developed a NAI protocol using mitoxantrone, 5-FU plus folinic acid (FA) and mitomycin C (MFFM). The response rates of HAI with 5-FU plus FA or MFFM were 45% and 66%, the interim median survival times 19.8 months and 27.4 months. 5-Year survivors were observed in all our protocols. Since no severe hepatotoxici ty occurred, 9 of 74 patients were resected after response to HAI with 5-FU plus FA or MFFM, without surgical mortality and with survival times from 2 + months to 58+ months. Conclusion: The high response rates, the long survi val times, the possibility of achieving 5-year-survival either by HAI alone or by resection after down staging with HAI all sum up to the evidence tha t HAI could be the primary choice of treatment for CRLM. Phase-III trials a re conducted to compare the protocols with optimal regional versus systemic chemotherapy.