Chemotherapy regimens before 2000

The North Central Cancer Treatment Group conducted a randomized trial comparing surgical resection alone with postoperative levamisole or levamisole/5-FU.[11][Level of evidence A1]

The North Central Cancer Treatment Group conducted a randomized trial comparing surgical resection alone with postoperative levamisole or levamisole/5-FU.[11][Level of evidence A1]

A significant improvement in disease-free survival (DFS) was observed for patients with stage III colon cancer who received levamisole/5-FU, but OS benefits were of borderline statistical significance.

The North Central Cancer Treatment Group conducted a randomized trial comparing surgical resection alone with postoperative levamisole or levamisole/5-FU.[11][Level of evidence A1]

An absolute survival benefit of approximately 12% (49% vs. 37%) was seen in patients with stage III disease treated with levamisole/5-FU.

In a large confirmatory intergroup trial, levamisole/5-FU- prolonged DFS and OS in patients with stage III colon cancer compared with patients who received no treatment after surgery.[12][Level of evidence A1] Levamisole alone did not confer these benefits.

Subsequent studies tested the combination of 5-FU/leucovorin (5-FU/LV) in the adjuvant treatment of patients with resected carcinoma of the colon.

Subsequent studies tested the combination of 5-FU/leucovorin (5-FU/LV) in the adjuvant treatment of patients with resected carcinoma of the colon.

Results of multiple randomized trials that have enrolled more than 4,000 patients comparing adjuvant chemotherapy with 5-FU/LV to surgery or 5-FU/semustine/vincristine demonstrate a relative reduction in mortality of between 22% and 33% (3-year OS of 71%–78% increased to 75%–84%).[13-15]

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

The Mayo Clinic regimen administered for a total of six cycles.

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

The Roswell Park regimen administered for a total of four cycles.

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

The Mayo Clinic regimen administered with levamisole for six cycles.

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

The levamisole regimen administered for a total of 1 year.

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

Five-year OS ranged from 49% for the Mayo Clinic regimen with levamisole to 60% for the Mayo Clinic regimen, and there were no statistically significant differences among treatment arms.[16][Level of evidence A1]

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

A preliminary report in November 1997 demonstrated a statistically significant advantage for OS for the Mayo Clinic regimen with levamisole compared with the levamisole regimen. This difference became insignificant with longer follow-up.

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

Overall, grade 3 or greater toxicity occurred more frequently for the Mayo Clinic regimen and the Mayo Clinic regimen with levamisole. In addition, the Mayo Clinic regimen was significantly more toxic with levamisole than without levamisole.

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

The death rate for all four regimens ranged from 0.5% to 1%.

The completed Intergroup trial 0089 (INT-0089 [NCT00201331]) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms:[16]Results:

Because of its ease of use and its good toxicity profile, the Roswell Park regimen became the preferred adjuvant regimen used in the United States and was often the control arm in subsequent randomized studies.

In addition to INT-0089, multiple studies have refined the use of 5-FU/LV in the adjuvant setting and can be summarized as follows:

In addition to INT-0089, multiple studies have refined the use of 5-FU/LV in the adjuvant setting and can be summarized as follows:

Levamisole is unnecessary when using leucovorin.[16]

In addition to INT-0089, multiple studies have refined the use of 5-FU/LV in the adjuvant setting and can be summarized as follows:

Treatment that includes 6 to 8 months of 5-FU/LV is equivalent to 12 months of therapy.[17-19]

In addition to INT-0089, multiple studies have refined the use of 5-FU/LV in the adjuvant setting and can be summarized as follows:

Treatment that includes 24 weeks of adjuvant 5-FU/LV is equivalent to 36 weeks of therapy.[20]

In addition to INT-0089, multiple studies have refined the use of 5-FU/LV in the adjuvant setting and can be summarized as follows:

High-dose leucovorin is equivalent to low-dose leucovorin.[21]

In addition to INT-0089, multiple studies have refined the use of 5-FU/LV in the adjuvant setting and can be summarized as follows:

A meta-analysis of seven trials revealed no significant difference in efficacy or toxicity among patients aged 70 years or younger compared with patients older than 70 years.[22]

In addition to INT-0089, multiple studies have refined the use of 5-FU/LV in the adjuvant setting and can be summarized as follows:

An infusional de Gramont bolus and infusional 5-FU/LV schedule is safer than a bolus modified Mayo Clinic schedule of 5-FU/LV.[20]