CMF Chemo Treatment: Cyclophosphamide + Methotrexate + Fluorouracil
If you’ve been diagnosed with early-stage breast cancer with lymph node involvement, your doctor may recommend that you receive CMF chemotherapy.
CMF is a chemotherapy regimen that consists of:
Your recommended chemo regimen will be based on the type of breast cancer you have. The type and stage of cancer will also influence whether it will be given before or after surgery.
CMF was one of the earliest chemotherapy regimens used to treat breast cancer, but it isn’t commonly used today.
In clinical trials, AC chemo was shown to be therapeutically equivalent to — meaning it works just as well as — CMF, with the benefit of taking less time.
AC-T may also be prescribed if the cancer is node-positive, but CMF is a better option for people with pre-existing heart conditions (though cardiotoxicity is a rare side effect of Taxol).
How CMF chemo works
The three medications in the CMF regimen work in different ways to stop cell division:
Cytoxan damages DNA in breast cancer cells, which stops the cells from dividing and causes them to die.
Methotrexate disrupts the activity of the nutrient folate, which throws off DNA replication. The medicine’s ability to interfere with this process stops cell division and leads to cell death.
Fluorouracil prevents DNA in rapidly dividing cells from making copies and disrupts DNA repair, leading the cells to die.
How CMF chemo is given
CMF can be given in one of three ways.
If you receive a CMF infusion, you’ll get the medications together on the first day of your treatment. Typically, you’ll get them again the following week (on day 8) and then have a rest period for three weeks. This 28-day cycle is usually repeated four to six times over four to six months.
Another way of giving CMF by infusion is to administer all three medications on the first day of treatment, followed by a three-week rest period. This 21-day cycle is repeated six to eight times over eighteen to 24 weeks.
Another option is to receive methotrexate and fluorouracil by injection on the first and eighth day of treatment, with Cytoxan taken as a tablet daily for two weeks. After two weeks, you will have a two-week rest period. This cycle will repeat four to six times over three to six months.
CMF chemo side effects
While on CMF chemo, you may experience any of the common side effects of Cytoxan, Methotrexate, or Fluorouracil. These include:
Less common side effects include:
Your doctor may give you folinic acid tablets if you experience extreme mouth or eye soreness or severe diarrhea.
CMF is not safe during pregnancy, as each medication has the potential to cause fetal harm. It’s also not recommended if you’re breastfeeding — the drugs can be passed through breast milk.
Real patient reviews
Members of our community discuss their experiences with CMF in the community forum. Here are some of their comments. Remember, it's very important to talk to your doctor about any side effects you're having and ask about ways to manage them.
“I am 7 years out from stage 2b, HER-2 negative. I chose CMF instead of AC because of the long-lasting side effects of AC. I also had a double mastectomy, 14 nodes removed, radiation, and 5 years of tamoxifen. I don’t regret my decision but still worry about a recurrence, like I’m sure anyone with a BC diagnosis would. CMF was not a cakewalk, but I didn’t get sick from it, just very tired, bit of brain fog, and some constipation. I do not have any long-lasting effects from CMF and didn’t lose my hair, which was nice.” —barbara510
“I finished the first 2 treatments of CMF, 2 Mondays in a row. Now I get a few weeks off before I do it again. The first week I was very tired and generally just didn't feel good for about 4 days, then I was fine. The 2nd week was not as easy. I was extremely tired, plus being somewhat constipated, queasy, and weak. Then having diarrhea and tired, not sleeping well. I was able to eat ok for the most part. I was able to get the important things done each day but it was a push. This lasted for 6 days and by Sunday I was fine.” — rosiesu
“I was diagnosed with a Stage I, Grade 3 IDC, ER+/PR+, HER2-, 0/15 nodes. My tumor was 8mm. I was 50 at diagnosis, but had been menopausal for 21 years. I took HRT for 16 of them. I was told that although my tumor was small, it was extremely aggressive and chemo was recommended. It was my choice which protocol to use - either CMF or AC/T. Since I had such a high chance of recurrence after treatment, I chose to do CMF, saving AC/T in the arsenal should I need it.” — survivor98
Read more in our CMF discussion forum.
Paying for CMF chemo
The cost of CMF chemo may vary. The price you’ll pay depends on your health insurance provider and plan, where you live, and the pharmacy you use.
Note: Your insurance company may require you to get prior authorization before covering CMF.
If you have trouble paying for CMF, ask your pharmacist or care team about financial assistance programs that may be able to help.
Learn more about financial assistance and medicine cost-lowering tips.
— Last updated on March 29, 2025 at 5:13 PM