Intraportal chemotherapy in colorectal carcinoma as an adjuvant modality

Abstract

Liver metastases of colorectal origin arise from malignant cells entering the portal venous circulation. Four hundred sixty patients from 7 participating institutions have been entered in a prospective randomized trial to assess the value of adjuvant portal venous infusion to prevent liver metastases following curative colorectal cancer surgery. By preoperative randomization, patients were assigned to surgery alone (control arm) or to portal liver infusion with 5‐fluorouracil (5‐FU) (500 mg/m2 daily × 7, continuous infusion during the first 7 postoperative days) and mitomycin C (10 mg/m2, 24 hours postoperatively as a 2‐hour infusion). A portal venous catheter was placed through any side branch of the mesenteric venous system during laparotomy for the primary tumor. Using the transabdominal route, there have been no catheter‐related complications. Despite a large cumulative dose of 5‐FU given during the immediate postoperative period, the systemic side effects were minimal. Overall hospital mortality in this study was 1.85% and was not influenced by the adjuvant treatment. This rate is considerably lower than that reported by previous multicenter trials and by the surgical literature, and it indicates an advance in surgical technique and pre‐/postoperative patient management in this type of elective surgery.Three hundred seventy‐eight patients (187 controls, 191 infusion patients) are completely evaluable for recurrence and survival. After a median follow‐up of 24 months, 43 recurrences have been observed in the control group and 34 in the infusion group (p<0.05). Liver metastases were present in 18 control patients and in 14 infusion patients. Twenty‐five patients in the control group and 18 patients in the infusion group died of recurrent disease. Due to the low number of recurrences in this study, it is too early to draw survival conclusions.Several controlled trials using adjuvant portal infusion are in progress. They also showed the feasibility of this approach and they suggested that adjuvant cytotoxic liver infusion may reduce the incidence of liver metastases without significantly increasing morbidity and mortality. It is too early, however, to recommend adjuvant portal infusion outside a clinical trial setting and such treatment should still be restricted to well‐designed prospective protocols.

Adjuvant portal liver infusion in colorectal cancer with 5-fluorouracil/heparin versus urokinase versus control results of a prospective randomized clinical trial (colorectal adenocarcinoma trial I)

“…37 Inconvenient morbidity was only seen in the 5-FU/ heparin group: five had stomatitis and one patient experienced alopecia (7%); nausea, vomiting, and diarrhea was seen in all groups with a majority in the infusion groups, according to the other above mentioned studies. Hospital stay was not significantly delayed in the infusion groups.…”

“…A recommendation for future studies of adjuvant cytotoxic portal infusion could be exclusion for patients older than 75 years of age, for insulin-dependent diabetes patients, and for patients with any evidence of intraabdominal sepsis at laparotomy or during the early postoperative period. 37 Inconvenient morbidity was only seen in the 5-FU/ heparin group: five had stomatitis and one patient experienced alopecia (7%); nausea, vomiting, and diarrhea was seen in all groups with a majority in the infusion groups, according to the other above mentioned studies. Hospital stay was not significantly delayed in the infusion groups.…”

“…published the data of these studies to which we add our new data ( Table 5). 37 All trials are randomized with a "no treatment" control group and all (except the study of Taylor et aL9 in Liv-erpool) are multicentric, and some do not include rectal cancer. In all studies a radical en bloc resection of the primary tumor and regional lymph nodes was performed, and portal venous catheterization was done at laparotomy through various routes according to the protocol or the surgeon's preference.…”

Effect of oral adjuvant therapy with Carmofur (HCFU) for distant metastasis of colorectal cancer

“…Many controlled studies have been conducted, mainly in the United States to investigate postoperative adjuvant chemotherapy for colorectal cancer, with several reports showing its effectiveness. [2][3][4] In 1990, Moertel et al 5 showed the efficacy of therapy with levamisole plus 5-FU, which was determined to be a standard therapy for colorectal cancer by the Meeting of of National Cancer Institute and National Institute of Health. 6 However, most of these studies used the intravenous route.…”

Adjuvant chemotherapy for colorectal cancer

“…However, the only published meta-analysis, that of Metzger et al [46], which pooled nine studies and 4437 patients, showed a very small but significant increase in survival for regional adjuvant chemotherapy compared with surgery alone.…”