Results of a Prospective Ramdomized Study of Hepatic Artery Infusion with 5-Fluorouracil vs. Intravenous 5-Fluorouracil in Patients with Hepatic Metastases from Colo-rectal Cancer

Grage, Theodor B.; Shingleton, William W.; Jubert, Andre V.; Elias, Elias G.; Aust, J. Bradley; Moss, Scot E.

doi:10.1159/000402318

Cited by 40 publications

(41 citation statements)

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“…The most consistently active agent for this disease has been 5-fluorouracil (5-FU), and most regimens have been based on this agent (Table 2). [17][18][19][20][21][22][23][24][25] Few studies, and certainly none of the most recent studies, have specifically examined the role of systemic chemotherapy for resectable liver disease. However, it is clear that for most chemotherapeutic regimens, less than one third of patients with liver metastases have shown any response.…”

Section: Results Of Medical Treatment Of Isolated Liver Metastatic DImentioning

confidence: 99%

Surgical treatment of colorectal metastases to the liver

Fong

Blumgart

Cohen

1995

CA: A Cancer Journal for Clinicians

124

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Section: Results Of Medical Treatment Of Isolated Liver Metastatic DImentioning

confidence: 99%

Surgical treatment of colorectal metastases to the liver

Fong

Blumgart

Cohen

1995

CA: A Cancer Journal for Clinicians

124

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“…In the sarcoma model, the complete surgical removal of the tumor as early as Day 5 after tumor inoculation failed to cure mice and only extended median survival time by 15 days (23). Additionally, systemic and hepatic arterial infusion chemotherapy in the management of liver metatases is also of limited value (30). It is clear that alternative approaches to the treatment of hepatic metastases are required.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease

et al. 1985

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Glucan, a particulate beta-1,3-polyglucose immunomodulator, was evaluated for its ability to modify hepatic metastases and survival in mice with reticulum cell sarcoma. Sarcoma M5076 cells were injected subcutaneously (1 X 10(5) cells) into syngeneic C57BL/6J male mice. On Day 20, histopathological studies indicated the presence of hepatic micrometastases. At this time, glucan (0.45 mg per mouse) or dextrose was administered intravenously. Therapy was continued at 3-day intervals up to Day 50. By Day 36 postchallenge, the glucan-treated group, when compared to the control group, showed a marked decrease in hepatic metastases, both grossly and histopathologically. A significant inhibition in the growth of the primary tumor also occurred. Plasma clearance of bromosulfophthalein measured on Day 36, denoted that glucan therapy maintained hepatic parenchymal cell functional integrity, while a 4-fold impairment in bromosulfopthalein removal was observed in control mice. Glucan-treated mice showed a 28% (p less than 0.05) long-term survival. In contrast, control mice showed a 100% mortality by Day 42 postchallenge. Studies to evaluate the mechanism of the anti-metastatic action of glucan indicated that 8 days after glucan administration, isolated hepatic macrophages were significantly more cytotoxic to sarcoma cells in vitro than were normal Kupffer cells. At this time, the cytotoxic activity of peritoneal and splenic macrophages from glucan-treated mice were unaltered. Additionally, co-incubation of particulate glucan with diverse populations of normal or tumor cells in vitro indicated that glucan exerted a direct cytostatic effect on sarcoma and melanoma cells and, in contrast, had a proliferative effect on normal spleen and bone marrow cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The disappointing results of regional chemotherapy demonstrated by these randomised trials has, not surprisingly, led to considerable controversy concerning the value of this approach to the treatment of patients with hepatic metastases (Kemeny, 1992;O'Connell, 1992 (Grage et al, 1979); MSKCC, Memorial Sloan Kettering Cancer Centre (Kemeny et al, 1987); NCOG, Northern California Oncology Group (Hohn et al, 1989) be achieved. However, co-administration of these drugs has been prematurely abandoned because of an unacceptably high frequency of arterial thrombosis.…”

Section: Pharmacological Rationale For Regional Chemotherapymentioning

confidence: 99%

Hepatic arterial chemotherapy for metastatic colorectal carcinoma

Takats

Kerr²,

Poole³

et al. 1994

Br J Cancer

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Summary In this review, the rationale of regional chemotherapy for treatment of hepatic metastases in advanced colorectal carcinoma is discussed. Pharmacokinetic principles and early clinical experience of hepatic arterial drug administration are summarised. The regional advantage of fluoropyrimidine compounds in this setting is well established, and recent evidence suggests that 5-fluorouracil (5-FU) is more efficacious than the analogue 5-fluoro-2'-deoxyuridine (FUDR). However, while significantly higher clinical response rates can be achieved with hepatic arterial infusion (HAI) chemotherapy compared with conventional intravenous drug administration, patient survival benefit is not significantly different. Several novel approaches to overcome the limitations of HAI therapy are currently being explored. These include concomitant use of biodegradable microspheres, which both slow tumour blood flow and enhance tumour drug uptake, and use of vasoactive agents to redistribute arterial blood flow towards tumours. In addition, novel chemotherapeutic agents which exploit unique biological characteristics of hepatic tumours are entering clinical trial.The conventional notion of chemotherapy is of a truly systemic treatment designed to combat widely disseminated malignant disease. Colorectal carcinoma is relatively unresponsive to chemotherapy (Mayer, 1992), despite an increasing understanding of drug mechanisms of action at the molecular level. To date, systemic 5-FU plus folinic acid is considered the optimum treatment for metastatic colorectal cancer, yielding response rates of around 25% and median survival of around 12 months (Piedbois et al., 1992). These disappointing results reflect, in part, the narrow therapeutic ratio of 5-FU and the presence of associated severe systemic side-effects limiting dose escalation. Regional chemotherapy affords an alternative method of cytotoxic drug administration which circumvents the constraints of systemic administration, while introducing the concept of targeted drug delivery to metastatic disease localised to specific components of the body.Three levels of tumour targeting have been described (Widder et al., 1979): (1) selective drug delivery to the tumourbearing organ, (2) drug delivery biased to tumour rather than to normal tissue within that organ and (3) enhancement of uptake of cytotoxic drug by malignant cells. In this context, regional chemotherapy constitutes first-order targeting. Currently, the value of this method of drug delivery is being assessed in a number of different malignancies, but experience is greatest in the treatment of hepatic metastases from colorectal carcinoma.Colorectal carcinoma is the second most common malignancy in the UK and the cause of over 19,000 deaths per year. Epidemiological studies show that the incidence of colorectal carcinoma is increasing, with approximately 28,000 new cases now being diagnosed annually. Up to 50% of patients with colorectal carcinoma develop liver metastases, from which as many as 70% of patients will subsequen...

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Results of a Prospective Ramdomized Study of Hepatic Artery Infusion with 5-Fluorouracil vs. Intravenous 5-Fluorouracil in Patients with Hepatic Metastases from Colo-rectal Cancer

Cited by 40 publications

References 0 publications

Surgical treatment of colorectal metastases to the liver

Surgical treatment of colorectal metastases to the liver

Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease

Hepatic arterial chemotherapy for metastatic colorectal carcinoma

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