Randomized Trial of Surgery Versus Surgery Followed by Adjuvant Hepatic Arterial Infusion With 5-Fluorouracil and Folinic Acid for Liver Metastases of Colorectal Cancer

Lorenz, Matthias; Müller, Hans‐Helge; Schramm, H; Gassel, H.‐J.; Rau, H.; Ridwelski, K.; Hauss, Johann; Stieger, R; Jauch, Karl‐Walter; Bechstein, Wolf O.; Encke, A.

doi:10.1097/00000658-199812000-00006

Cited by 343 publications

(171 citation statements)

References 31 publications

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“…Presently, there is no standard guideline for CLM patients after liver resection. There are a few randomised clinical trials published that evaluate the survival effects of HAI of FUdR and/or intravenous systemic chemotherapy after hepatic resection (Lygidakis et al, 1995;Asahara et al, 1998;Lorenz et al, 1998;Lorenz and Muller, 2000;Tono et al, 2000;Kemeny et al, 2002;Kemeny and Gonen, 2005;Portier et al, 2006). Most of these studies, however, have limited statistical power due to small sample sizes (less than 100 subjects) or slow accrual.…”

Section: Discussionmentioning

confidence: 99%

Predictors of survival after hepatic resection among patients with colorectal liver metastasis

et al. 2007

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Studies suggest improved survival following resection of colorectal cancer liver metastases (CLMs). We investigated predictors of survival among patients with CLM who underwent hepatic resection using the SEER-Medicare database to identify patients X65 years diagnosed with CLM, 1991CLM, -2003, who underwent hepatectomy. Cox proportional hazards models were used to identify factors associated with survival after hepatectomy. Of 923 patients with CLM who underwent hepatectomy, 514 were stages I -III and developed CLM46 months after diagnosis (metachronous), and 409 were stage IV with CLM at diagnosis (synchronous). From the date of hepatectomy, 5 year survival was 22%; younger age, being married, female gender, surgery in an NCI-designated cancer centre, fewer comorbidities, fewer positive lymph nodes, and lower grade were associated with improved survival. Both 5-fluorouracil (5FU)-based chemotherapy and hepatic arterial infusion (HAI) of floxuridine-based chemotherapy following hepatectomy improved survival (HR ¼ 0.62, 95% CI: 0.50 -0.78; HR ¼ 0.51, 95% CI: 0.28 -0.97, respectively) in the synchronous, but not metachronous, group. The HR for overall mortality was higher in hospitals with a high vs low procedure volume (0.75, 95% CI: 0.58 -0.94). A substantial subgroup of patients with CLM who undergo hepatectomy experiences long-term survival. High hospital procedure volume and use of 5FU-based or HAI-based chemotherapy after resection were associated with improved prognosis.

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Section: Discussionmentioning

confidence: 99%

Predictors of survival after hepatic resection among patients with colorectal liver metastasis

et al. 2007

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“…Many reports have demonstrated that recent chemotherapy including leucovorin (LV) and 5-fluorouracil (5FU) combined with irinotecan (CPT-11) or oxaliplatin have survival benefits for patients with advanced colorectal cancer including unresectable liver metastasis (25)(26)(27)(28), but the survival impact of hepatic arterial infusion chemotherapy is still controversial (29)(30)(31)(32). The strategy for patients with unresectable liver metastases after neoadjuvant chemotherapy has been a major breakthrough (4).…”

Section: Discussionmentioning

confidence: 99%

Potential predictors of survival after surgery for colorectal cancer patients with synchronous unresectable liver metastases

Hotta

Takifuji²,

Uchiyama³

et al. 2006

Oncol Rep

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Abstract. Liver resection has been recognized as the best treatment for patients with colorectal liver metastases, but as a curative resection for multiple and bilobar colorectal liver metastases (MBCLM) it is definitely less effective. We clarify predictors of survival for unresectable MBCLM. Potential predictors of overall survival, and the correlation between tumor marker and survival were evaluated for patients with synchronous unresectable MBCLM, including 6 rectal and 17 colon cancers. In univariate analysis, survival in patients with the following parameters were longer than those without them: number of liver metastases (≤10), without lung metastasis and peritoneal invasion, and with a <1.0 ratio of postoperative CEA/preoperative CEA. In multivariate analysis, the numbers of liver metastases (>10) and a >1.0 ratio of postoperative CEA/preoperative CEA were factors of poor prognosis, and patients with two such factors had an even worse prognosis. There was a tendency for correlation between the ratio of postoperative CEA/pre-operative CEA and survival (R=-0.492, P=0.053; y=17.388-3.733x). Thus, we clarified some of the predictors of survival for MBCLM, and the usefulness of serum CEA.

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“…Significantly more patients were free of liver recurrence (46% vs. 25%) or any recurrence (67% vs. 43%) in the combined therapy arm, but because of limited sample size, prolongation of survival could not be demonstrated. In another trial comparing HAI of 5-fluorouracil and leucovorin versus observation in patients after liver resection there was no evidence of improved survival with the use of HAI, but, like many trials in patients with unresectable metastases, a significant proportion of patients randomized to HAI were never treated 104 . Adjuvant administration of HAI after liver resection has also been explored in combination with systemic administration of other drugs or in regimen alternating HAI with systemic chemotherapy.…”

Section: Hai and Other Liver-directed Proceduresmentioning

confidence: 96%

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

Melichar¹

2012

BIOMED PAP

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Background. Historically, metastatic colorectal carcinoma was regarded as a tumor that is relatively resistant to cytotoxic agents. Due to the limited number of treatment options, methods have been investigated to enhance selectivity. One method for enhancing selectivity is anatomical targeting, including hepatic arterial infusion (HAI). Methods. A comprehensive review of the literature. Results. Early studies with HAI used fluoropyrimidines, 5-fluorouracil or floxuridine. Several randomized trials comparing the HAI of fluoropyrimidines with systemic administration of fluoropyrimidines or best supportive care that were conducted in the 1980s and early 1990s demonstrated a superior objective response rate, but usually not a prolongation of survival in patients treated with HAI. The current standard of first line systemic chemotherapy of metastatic colorectal carcinoma is combination chemotherapy (fluoropyrimidines, oxaliplatin and/or irinotecan) administered with targeted agents. A number of trials have reported promising activity of the HAI of oxaliplatin and/or irinotecan with fluoropyrimidines, but only pilot studies are available for the combination of HAI of cytotoxic agents with targeted drugs. Factors that limit the effectiveness and utilization of HAI include catheter or port system-related complications, the presence of extrahepatic metastases, or increased risk of hepatic toxicity. Conclusions. HAI could be considered in clinical practice in different settings, including patients after liver resection, as second line therapy in patients failing standard front line regimens and as neodjuvant therapy to convert to resectability. Future studies should specifically concentrate on identifying regimens that would result in increased cure rates in patients with isolated hepatic metastases. For this reason, exploiting anatomical selectivity may still be a useful approach, even in the era of targeted therapy.

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Randomized Trial of Surgery Versus Surgery Followed by Adjuvant Hepatic Arterial Infusion With 5-Fluorouracil and Folinic Acid for Liver Metastases of Colorectal Cancer

Cited by 343 publications

References 31 publications

Predictors of survival after hepatic resection among patients with colorectal liver metastasis

Predictors of survival after hepatic resection among patients with colorectal liver metastasis

Potential predictors of survival after surgery for colorectal cancer patients with synchronous unresectable liver metastases

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

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