Why Use Of This Common Chemo Drug Has Decreased Over The YearsC. Dixon
When you’re told you’ll need chemo as part of your cancer treatment regimen, it’s important to understand what types you’ll be given. Your doctor will create a treatment plan that takes into account the stage of your cancer, the type and aggressiveness, and your overall health. There are over 100 different types of chemo, and they can be used alone or in combination with one another to treat the unique conditions of your specific cancer.
Each type comes with its own set of side effects and potential issues.
A popular class of chemo drugs called anthracyclines has been a go-to for doctors for decades. However, in addition to increased severity of short term side effects like nausea, vomiting, and hair loss, anthracyclines also come with an increased risk of concerning long-term side effects, like cardiotoxicity and leukemia.
But because it is effective against some specific types of cancers and studies have shown mixed results over the years, anthracyclines are still in use today.
Rise To Fame
Anthracyclines debuted in the ’80s and quickly rose in popularity throughout the ’90s. This group includes doxorubicin (Adriamycin — nicknamed ‘the red devil’ because of its red color), epirubicin (Ellence), pegylated liposomal doxorubicin (Doxil), daunorubicin (Cerubidine and DaunoXome), and mitoxantrone (Novantrone).
In the ’90s, the results of 11 clinical trials showed that anthracyclines slightly improved survival rates overall; the interesting thing is, when looked at individually, the results were inconclusive.
But its popularity continued to climb. By 2000, anthracyclines had become the chemo type of choice. Over 80% of women under 70 who had cancer spread to their lymph nodes were treated with anthracycline-based chemo, and over 70% of women under 70 without lymph node involvement had anthracycline-based chemo.
However, by 2008, anthracycline use was not part of the initial chemo plan for most breast cancer patients, a trend which has continued.
Mixed Results and Decreased Popularity
The efficacy of anthracyclines compared to other chemo treatments has been studied several times, often with mixed or conflicting results. It is often compared to (or used with) a group of chemo drugs called taxanes, which include Taxol and Taxotere.
Since 2005, the use of taxane-based chemotherapy has increased significantly as a replacement for anthracycline-based therapy. Taxanes have their own set of side effects, and can also lead to neuropathy, which may or may not go away with time, and can lead to other complications. However, they don’t cause a significant increase in either cardiotoxicity or leukemia, like anthracyclines do.
In trials where anthracyclines do seem to improve outcomes, it is often statistically insignificant, and they are not used alone.
One study concluded that a regimen including taxanes and anthracyclines was slightly more effective than one without anthracyclines against a very specific type of cancer: HER2-negative breast cancer that is still in its early stages but also has a high risk of recurrence. 92.4% of the combination group had no recurrence of invasive breast cancer, while 91.7% of the non-anthracycline group had no recurrence.
Another study showed that, when combined with a popular HER2-positive treatment called trastuzumab (Herceptin), anthracyclines lowered the chance of metastasis — but, not in a statistically significant way. And, alarmingly, it showed that women who received both had five times as many cases of congestive heart failure as the group not receiving any anthracyclines. The good news is, the chances of severe cardiac dysfunction can be greatly reduced if the patient is pretreated with lisinopril or carvedilol, which you can learn more about here.
In a third study, US Oncology Research Trial 9735, 1,016 women were given either four cycles of Taxotere (a taxane) and cyclophosphamide or four cycles of Adriamycin (an anthracycline) and cyclophosphamide. After 7 years, the survival rate in the taxane group was significantly higher than the anthracycline group.
The Ugly Side Effects
The side effects of anthracyclines include nausea and vomiting; mouth sores, hair loss; pain in the injection site; fatigue; poor concentration; bladder irritation; and menopausal symptoms. A study published in JAMA Oncology in late 2015 found that women treated with anthracyclines had lower verbal memory and struggled with information processing compared to women on a non-anthracycline regimen or women who did not have any chemo treatment.
Cardiotoxicity used to be a serious concern of any chemo treatment, but that has decreased over the years as awareness has been raised and doses have been adjusted. However, anthracyclines do still come with a higher risk of heart damage than other chemo treatments: about 1%-2% of patients experience it. In addition, anthracyclines also come with an increased risk of leukemia, with under 1% experiencing it.
Over the years, the potentially devastating long-term effects of anthracyclines and lukewarm study results have contributed to the decline in its use. One thing doctors and researchers can agree on about anthracyclines is that any resulting toxicity is lessened with lower doses and when combined with other treatments.
Cancer treatment is far from perfect, but researchers are getting closer and closer to using less-toxic methods. Every type of chemo comes with its own set of pitfalls and benefits. If you’re concerned about the type of chemo you’re getting, reach out to your doctor.