Adjuvant chemotherapy with 4 cycles of doxorubicin (Adriamycin), and cyclophosphamide (Cytoxan, C), followed by 4 cycles of paclitaxel (Taxol).
1) What is a cycle? It is a 3-week period. This is the basic plan of the cycles.
2) The total plan of 4 cycles of AC and 4 cycles of T and is planned to take 24 weeks to complete.
3) What side effects might be expected? This should be discussed with your doctor. It depends on your individual health and resistance to side effects, and what medicines you receive to prevent these side effects. On most days during therapy most people can do what they normally do, but side effects can on some days cause serious discomfort and even lead to hospitalization. You should know that most side effects are temporary, but some can be permanent and rare ones can cause death.
As of the time of the writing of this sheet (April 2003) the toxicity information for the major study of AC followed by Taxol chemotherapy has not been published in as detailed form as might be ideal. The one study that has been published included about 3000 women, 1500 of whom got both 4 cycles of AC and 4 cycles of Taxol, and 1500 of whom got only 4 cycles of AC. The analysis of this study showed that the 4 cycles of Taxol were better tolerated than the 4 cycles of AC, but that both parts of the regimen had risks that needed to be considered.
The following tables show how many women out of 100 had side effects of different kinds during the AC part of the therapy and during the Taxol part of the therapy. For example, for nausea, for 100 women getting the Adriamycin/ cyclophosphamide part of the therapy, 32 women might expect to have some days with moderate, severe or very severe nausea. For nausea, for 100 women getting the Taxol part of the therapy only 3 women would have this problem.
Side effects during the Adriamycin/cyclophosphamide treatments (number of women out of 100 having this problem at least once).
Side effects during the Taxol treatments (number of women out of 100 having this problem at least once).
Low white cells do not cause any symptoms. Because white blood cell's purpose is defend you from infections, during periods of low blood counts you are at higher risk of infection. Granulocytes are a special type of white blood cell that has the purpose of defending you from bacteria. During therapy with the Adriamycin/Cyclophosphamide 17 out of 100 women developed potentially serious infections that required antibiotics. During therapy with the Taxol 11 out of 100 women developed potentially serious infections that required antibiotics.
In a study in the 1500 women who got Taxol there were some rare but very serious side effects. One of the potentially serious side effects of Taxol is allergic reactions. These reactions occurred in 6% of the women in the study. If an allergic reaction is going to occur it usually happens during the intravenous treatment. Your health care team will give you medicines to decrease the risk of this, but it still sometimes occurs. Although most patients who had allergic reactions to Taxol had mild symptoms such as hives, fever, and shortness of breath, there were some patients who developed very severe allergic reactions. 4 women developed very severe allergic reactions during treatment (0.3%) and 1 woman died of the allergic reaction (0.1%).
Taxol can also cause “peripheral neuropathy”. This is usually a mild numbness (or tingling) in the fingers and toes. 15% of the women in the 1570 woman study developed this type of mild neuropathy. 3% of the women developed a more severe form which interfered with their normal functioning. If this type of problem occurs it typically gets better over a few weeks after stopping therapy. One rare side effect of Taxol can be a “motor neuropathy” which can cause weakness, which sometimes can be severe and cause disability. In the 1500 patients getting Taxol 1 patient developed permanent paralysis.
Although the doxorubicin used in these treatments can cause a small amount of decrease in the strength of the heart in most patients, this amount cannot be sensed, and does not cause any physical limitations. In the 3000 patients, 10 patients developed heart failure during treatment (0.3%), and 50 patients developed heart failure in the 3 years afterwards (1.5%). Some women
not getting chemotherapy might be expected to develop this problem, so it is not clear how much of this problem was caused by the doxorubicin, but it is likely that some of it was treatment related.
One possible severe side effect of this type of chemotherapy may be an increased risk of leukemia. In an analysis of 3000 patients 17 patients developed preleukemia or leukemia within 3 years of follow-up (0.6%).
More information about the side effects of this therapy can be found in the articles:
1) Henderson IC, Berry DA, Demetri GD, et al. Improved outcomes from adding sequential Paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node positive primary breast cancer. J Clin Onc 21: 976-983, 2003.
2) Shapiro CL, Recht A. Side-effects of adjuvant treatment of breast cancer. New England Journal of Medicine Volume 344, pages 1997-2008, 2001.
More information about the side effects of this therapy can be found in the Taxol package insert or the PDR (Physicians' Desk Reference).