Regional and systemic therapies for advanced colorectal carcinoma: Randomized clinical trial results

Al B Benson III*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The treatment of advanced colorectal cancer has been evaluated in a series of randomized trials, including infusional and modulated 5- fluorouracil (5-FU), and three meta-analyses encompassing trials of 5-FU plus leucovorin, continuous-infusion 5-FU, and intra-arterial fluoropyrimidines. A Southwest Oncology Group seven-arm phase II trial suggested that infusional 5-FU produced the most favorable toxicity spectrum and the longest survival, warranting further investigation in phase III trials. In a randomized phase III five-arm trial conducted by the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B, significant toxicity differences noted among the arms favored high-dose infusional 5-FU. In addition, the trial showed that 5-FU modulated by leucovorin or interferon was not more effective than 5-FU given as a 24-hour high-dose infusion weekly, and N-(phosphonacetyl)-L- aspartic acid did not enhance the activity of the weekly infusional 5-FU. Oral leucovorin provided no advantage over IV dosing. There was a significant difference in survival for patients with nonmeasurable disease (16.9 months) compared to those with measurable disease (12.6 months, P=.001). The Advanced Colorectal Cancer Meta-Analysis Project demonstrated a response advantage for patients receiving 5-FU plus leucovorin (23%) compared to those receiving bolus 5-FU (11%, P=10-7); however, there was no survival advantage of 5-FU pIus leucovorin over 5-FU alone (P=0.57). The Meta-Analysis Group in Cancer showed that continuous-infusion 5-FU resulted in a statistically significantly higher response rate than bolus 5-FU (22% vs 14%, P=.0002). Overall survival also favored continuous-infusion 5-FU (P=.04). Continuous- infusion 5-FU was less toxic than bolus treatment. Data from six select randomized trials comparing hepatic intra-arterial infusion of FUDR to systemic therapy demonstrated a significant difference favoring intra- arterial therapy. Future directions for the treatment of advanced colorectal cancer include ongoing trials comparing low-dose vs high-dose infusional 5- FU, intra-arterial FUDR, leucovorin and dexamethasone vs systemic leucovorin plus 5-FU and proposed trials evaluating the dihydropyrimidine dehydrogenase inhibitor eniluracil plus oral 5-FU. Other drugs of interest include UFT, capecitabine, thymidylate synthase inhibitors, oxaliplatin, and irinotecan combinations.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalOncology
Volume12
Issue number10 SUPPL. 7
StatePublished - Dec 5 1998

Fingerprint

Fluorouracil
Colorectal Neoplasms
Randomized Controlled Trials
Leucovorin
Therapeutics
Meta-Analysis
oxaliplatin
irinotecan
Survival
Dihydrouracil Dehydrogenase (NADP)
Intra Arterial Infusions
Thymidylate Synthase
Poisons
Aspartic Acid
Interferons
Dexamethasone

ASJC Scopus subject areas

  • Oncology

Cite this

@article{9e1d219a42af4f94af0e209bc73399e4,
title = "Regional and systemic therapies for advanced colorectal carcinoma: Randomized clinical trial results",
abstract = "The treatment of advanced colorectal cancer has been evaluated in a series of randomized trials, including infusional and modulated 5- fluorouracil (5-FU), and three meta-analyses encompassing trials of 5-FU plus leucovorin, continuous-infusion 5-FU, and intra-arterial fluoropyrimidines. A Southwest Oncology Group seven-arm phase II trial suggested that infusional 5-FU produced the most favorable toxicity spectrum and the longest survival, warranting further investigation in phase III trials. In a randomized phase III five-arm trial conducted by the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B, significant toxicity differences noted among the arms favored high-dose infusional 5-FU. In addition, the trial showed that 5-FU modulated by leucovorin or interferon was not more effective than 5-FU given as a 24-hour high-dose infusion weekly, and N-(phosphonacetyl)-L- aspartic acid did not enhance the activity of the weekly infusional 5-FU. Oral leucovorin provided no advantage over IV dosing. There was a significant difference in survival for patients with nonmeasurable disease (16.9 months) compared to those with measurable disease (12.6 months, P=.001). The Advanced Colorectal Cancer Meta-Analysis Project demonstrated a response advantage for patients receiving 5-FU plus leucovorin (23{\%}) compared to those receiving bolus 5-FU (11{\%}, P=10-7); however, there was no survival advantage of 5-FU pIus leucovorin over 5-FU alone (P=0.57). The Meta-Analysis Group in Cancer showed that continuous-infusion 5-FU resulted in a statistically significantly higher response rate than bolus 5-FU (22{\%} vs 14{\%}, P=.0002). Overall survival also favored continuous-infusion 5-FU (P=.04). Continuous- infusion 5-FU was less toxic than bolus treatment. Data from six select randomized trials comparing hepatic intra-arterial infusion of FUDR to systemic therapy demonstrated a significant difference favoring intra- arterial therapy. Future directions for the treatment of advanced colorectal cancer include ongoing trials comparing low-dose vs high-dose infusional 5- FU, intra-arterial FUDR, leucovorin and dexamethasone vs systemic leucovorin plus 5-FU and proposed trials evaluating the dihydropyrimidine dehydrogenase inhibitor eniluracil plus oral 5-FU. Other drugs of interest include UFT, capecitabine, thymidylate synthase inhibitors, oxaliplatin, and irinotecan combinations.",
author = "{Benson III}, {Al B}",
year = "1998",
month = "12",
day = "5",
language = "English (US)",
volume = "12",
pages = "28--34",
journal = "Oncology",
issn = "0890-9091",
publisher = "UBM Medica Healthcare Publications",
number = "10 SUPPL. 7",

}

Regional and systemic therapies for advanced colorectal carcinoma : Randomized clinical trial results. / Benson III, Al B.

In: Oncology, Vol. 12, No. 10 SUPPL. 7, 05.12.1998, p. 28-34.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regional and systemic therapies for advanced colorectal carcinoma

T2 - Randomized clinical trial results

AU - Benson III, Al B

PY - 1998/12/5

Y1 - 1998/12/5

N2 - The treatment of advanced colorectal cancer has been evaluated in a series of randomized trials, including infusional and modulated 5- fluorouracil (5-FU), and three meta-analyses encompassing trials of 5-FU plus leucovorin, continuous-infusion 5-FU, and intra-arterial fluoropyrimidines. A Southwest Oncology Group seven-arm phase II trial suggested that infusional 5-FU produced the most favorable toxicity spectrum and the longest survival, warranting further investigation in phase III trials. In a randomized phase III five-arm trial conducted by the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B, significant toxicity differences noted among the arms favored high-dose infusional 5-FU. In addition, the trial showed that 5-FU modulated by leucovorin or interferon was not more effective than 5-FU given as a 24-hour high-dose infusion weekly, and N-(phosphonacetyl)-L- aspartic acid did not enhance the activity of the weekly infusional 5-FU. Oral leucovorin provided no advantage over IV dosing. There was a significant difference in survival for patients with nonmeasurable disease (16.9 months) compared to those with measurable disease (12.6 months, P=.001). The Advanced Colorectal Cancer Meta-Analysis Project demonstrated a response advantage for patients receiving 5-FU plus leucovorin (23%) compared to those receiving bolus 5-FU (11%, P=10-7); however, there was no survival advantage of 5-FU pIus leucovorin over 5-FU alone (P=0.57). The Meta-Analysis Group in Cancer showed that continuous-infusion 5-FU resulted in a statistically significantly higher response rate than bolus 5-FU (22% vs 14%, P=.0002). Overall survival also favored continuous-infusion 5-FU (P=.04). Continuous- infusion 5-FU was less toxic than bolus treatment. Data from six select randomized trials comparing hepatic intra-arterial infusion of FUDR to systemic therapy demonstrated a significant difference favoring intra- arterial therapy. Future directions for the treatment of advanced colorectal cancer include ongoing trials comparing low-dose vs high-dose infusional 5- FU, intra-arterial FUDR, leucovorin and dexamethasone vs systemic leucovorin plus 5-FU and proposed trials evaluating the dihydropyrimidine dehydrogenase inhibitor eniluracil plus oral 5-FU. Other drugs of interest include UFT, capecitabine, thymidylate synthase inhibitors, oxaliplatin, and irinotecan combinations.

AB - The treatment of advanced colorectal cancer has been evaluated in a series of randomized trials, including infusional and modulated 5- fluorouracil (5-FU), and three meta-analyses encompassing trials of 5-FU plus leucovorin, continuous-infusion 5-FU, and intra-arterial fluoropyrimidines. A Southwest Oncology Group seven-arm phase II trial suggested that infusional 5-FU produced the most favorable toxicity spectrum and the longest survival, warranting further investigation in phase III trials. In a randomized phase III five-arm trial conducted by the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B, significant toxicity differences noted among the arms favored high-dose infusional 5-FU. In addition, the trial showed that 5-FU modulated by leucovorin or interferon was not more effective than 5-FU given as a 24-hour high-dose infusion weekly, and N-(phosphonacetyl)-L- aspartic acid did not enhance the activity of the weekly infusional 5-FU. Oral leucovorin provided no advantage over IV dosing. There was a significant difference in survival for patients with nonmeasurable disease (16.9 months) compared to those with measurable disease (12.6 months, P=.001). The Advanced Colorectal Cancer Meta-Analysis Project demonstrated a response advantage for patients receiving 5-FU plus leucovorin (23%) compared to those receiving bolus 5-FU (11%, P=10-7); however, there was no survival advantage of 5-FU pIus leucovorin over 5-FU alone (P=0.57). The Meta-Analysis Group in Cancer showed that continuous-infusion 5-FU resulted in a statistically significantly higher response rate than bolus 5-FU (22% vs 14%, P=.0002). Overall survival also favored continuous-infusion 5-FU (P=.04). Continuous- infusion 5-FU was less toxic than bolus treatment. Data from six select randomized trials comparing hepatic intra-arterial infusion of FUDR to systemic therapy demonstrated a significant difference favoring intra- arterial therapy. Future directions for the treatment of advanced colorectal cancer include ongoing trials comparing low-dose vs high-dose infusional 5- FU, intra-arterial FUDR, leucovorin and dexamethasone vs systemic leucovorin plus 5-FU and proposed trials evaluating the dihydropyrimidine dehydrogenase inhibitor eniluracil plus oral 5-FU. Other drugs of interest include UFT, capecitabine, thymidylate synthase inhibitors, oxaliplatin, and irinotecan combinations.

UR - http://www.scopus.com/inward/record.url?scp=0031761872&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031761872&partnerID=8YFLogxK

M3 - Article

C2 - 9830622

AN - SCOPUS:0031761872

VL - 12

SP - 28

EP - 34

JO - Oncology

JF - Oncology

SN - 0890-9091

IS - 10 SUPPL. 7

ER -