DNA Mismatch Repair and 5-FU: What’s the Connection?

Some colon cancer patients don’t benefit from treatment with 5-FU based chemotherapy and may even have worse outcomes than if they no chemo at all.

Of every 100 people with colon cancer, about 15 will have cancers that arise when mistakes in DNA during cell division are not caught and fixed.  Scientists call this defective mismatch repair or dMMR.

More often, colon cancer occurs when mutations in chromosomes accumulate but DNA repair pathways remain intact and mismatch repair is proficient (pMMR). This is true for about 85 percent of colon cancer.

Both prognosis and the potential benefit from FU-based chemotherapy appear to be very different for these two types of colon cancer. Knowing mismatch repair status of colon tumors can help patients and their doctors make better treatment decisions.

Patients with defective mismatch repair have better disease-free and overall survival and don’t seem to benefit from 5-FU at either stage II or stage III.  Stage II patients with dMMR have significantly poorer overall survival if they get chemo after surgery.

Caution:  These results come from studies of 5-FU plus levamisole or 5-FU plus leucovorin.  They don’t include any information from the current standard treatments of FOLFOX or FLOX which contain oxaliplatin in addition to 5-FU and leucovorin.

Continue reading…

Posted by Kate Murphy on July 13th, 2010
Posted in: Research & Treatment News | 3 Comments »
Tags: 5-FU, defective mismatch repair, MSI, prognosis, stage II colon cancer

XELOX Beats 5-FU with Fewer Recurrences

A combination of Xeloda and Eloxatin (XELOX) was better than standard 5-FU and leucovorin chemotherapy in reducing recurrences of stage III colon cancer after surgery.  Significantly more patients receiving XELOX were alive without cancer three years after treatment began.

Roche announced results of a Phase III clinical trial that compared XELOX chemotherapy to bolus 5-FU and leucovorin.  The trial, nicknamed XELOXA (NO16968), enrolled almost 1,900 patients in 29 countries.

Its primary goal was to see if combining the oral drug Xeloda® (capecitabine) with Eloxatin® (oxaliplatin) could improve disease-free survival for stage III colon cancer patients. Continue reading…

Posted by Kate Murphy on July 23rd, 2009
Posted in: Research & Treatment News | 2 Comments »
Tags: 5-FU, capecitabine, clinical trial results, Eloxatin, oxaliplatin, Xeloda

Comparing 5-FU or Capecitabine Combined with Oxaliplatin

Infusional 5-FU or oral Xeloda® (capecitabine) are two different drugs that can be combined with Eloxatin® (oxaliplatin) to treat colorectal cancer that has spread.  Six different randomized clinical trials have compared the two approaches.

Researchers analyzed a pool of all six trials to find out if one approach is better than the other. While they found that there are different side effects, the time until cancer gets worse (progression-free survival) and overall survival time are the same.

The percentage of patients who got infusional 5-FU  and had their tumors shrink (response rate) was greater than those who had shrinkage with capecitabine .  However, this did not translate into better progression-free interval or longer survival time. Continue reading…

Posted by Kate Murphy on December 9th, 2008
Posted in: Research & Treatment News | No Comments »
Tags: 5-FU, capecitabine, Xeloda

KRAS Status Doesn’t Impact Treatment with 5-FU Alone

While researchers have found that colorectal cancer tumors that have mutated KRAS genes don’t respond to treatment with EFGR inhibitors Erbitux®(cetuximab) and Vectibix™(panitumumab), is the same thing true for other drugs?

5-FU (fluorouracil) is the backbone of most colorectal cancer treatment, given alone or in combination with other drugs.  What does KRAS status mean when 5-FU is the only treatment? Continue reading…

Posted by Kate Murphy on August 2nd, 2008
Posted in: Research & Treatment News | No Comments »
Tags: 5-FU, KRAS, survival benefit

Switching from 5FU to Xeloda Can Cause Significant Side Effects

An immediate switch from 5-FU treatment to Xeloda® (capecitabine) for stage III colon cancer caused so much toxicity that a trial designed to test patient preferences for treatment had to be stopped.

Patients in the Patient Preference in Adjuvant Therapy (PACT) trial who switched after 6 weeks from weekly 5-FU with leucovorin to oral capecitabine experienced excessive side effects. The trial was designed to determine which approach to treatment patients liked best. Continue reading…

Posted by Kate Murphy on July 23rd, 2008
Posted in: Research & Treatment News | 12 Comments »
Tags: 5-FU, side effects, Xeloda