Oral Paclitaxel Plus Encequidar Offers Better Response Than IV Paclitaxel in Metastatic Breast Cancer
Metastatic breast cancer responded better to a combination of the chemotherapy medicine paclitaxel in pill form and encequidar (a medicine that allows oral paclitaxel to be absorbed into the bloodstream) than to intravenous paclitaxel, according to a study.
The research was published online on July 20, 2022 by the Journal of Clinical Oncology. Read the abstract of “Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer.”
Metastatic breast cancer is advanced-stage breast cancer that has spread to parts of the body away from the breast, such as the bones or liver.
Taxol is the brand name of paclitaxel, but the patent expired, meaning the medicine is available as a generic. Paclitaxel is a type of chemotherapy called a taxane. Taxanes work by interfering with a cancer cell’s ability to divide. Paclitaxel is usually combined with other chemotherapy medicines intravenously, which means the medicine is delivered directly into your bloodstream through an IV or a port.
To allow the medicine to enter the bloodstream, intravenous paclitaxel is mixed with solvents. These solvents can make it difficult for people to tolerate paclitaxel. To minimize any reactions to the solvents, people usually take steroids before receiving paclitaxel.
reduces the risk of early-stage breast cancer coming back
treats advanced-stage and metastatic breast cancer after it stops responding to other chemotherapy regimens
Paclitaxel also can cause a number of side effects, including infusion site reactions and neuropathy. Neuropathy is the general term for pain or discomfort caused by damage to the nerves of the peripheral nervous system. Your peripheral nervous system is made up of the many nerves that carry signals from the brain and spinal cord to other — or peripheral — parts of the body, such as the hands and feet.
Chemotherapy medicines like paclitaxel travel throughout the body, where they can cause nerve damage. When there is damage to nerves, it can affect the way the body sends signals to muscles, joints, skin, and internal organs and can cause:
loss of sensation
Neuropathy can greatly decrease quality of life.
There has been ongoing research to see if a pill or capsule form of paclitaxel would:
be easier for people to tolerate
cause fewer side effects
remove the need for people to take steroids beforehand
But because of paclitaxel’s chemical makeup, the body doesn’t absorb oral paclitaxel. So researchers developed encequidar — a type of medicine (called a P-glycoprotein pump inhibitor) that allows the body to absorb oral paclitaxel.
About the study
Earlier results from this study presented at the 2019 San Antonio Breast Cancer Symposium suggested that the combination of oral paclitaxel and encequidar caused a better response in metastatic breast cancer and less neuropathy than intravenous paclitaxel.
In this study, the researchers did their analysis after a longer follow-up time.
The study included 402 post-menopausal women from Latin America diagnosed with metastatic breast cancer.
None of the women had brain metastases, and none of the women had been treated with taxane chemotherapy within the past year.
The women joined the study between December 2015 and February 2019. Follow-up time was about 19 months.
The researchers randomly assigned the women to one of two treatment groups:
265 women took oral paclitaxel and encequidar three consecutive days each week
137 women received an IV infusion of paclitaxel that took three hours every three weeks
The dosing schedule for the oral paclitaxel is quite involved and stringent:
you must fast for four hours before taking the encequidar capsule
after taking the encequidar capsule, you must wait one hour before taking the paclitaxel capsules
after you take all the paclitaxel capsules, you must wait another four hours before eating
you must follow this schedule for three days in a row each week
The researchers wanted to see how the breast cancers responded to the two forms of paclitaxel.
36% of the cancers responded to oral paclitaxel
23% of the cancers responded to IV paclitaxel
This difference was statistically significant, which means it was likely due to the difference in treatment and not just because of chance.
The researchers also looked at progression-free survival and overall survival. Progression-free survival is how long the women lived without the cancer growing. Overall survival is how long the women lived, whether or not the cancer grew.
Progression-free survival was:
8.4 months for women taking oral paclitaxel and encequidar
7.4 months for women receiving IV paclitaxel
Overall survival was:
22.7 months for women taking oral paclitaxel and encequidar
16.5 months for women receiving IV paclitaxel
The rate of grade 3 and grade 4 side effects was about the same for all the women, no matter which type of paclitaxel they received.
Compared with women who received IV paclitaxel, women who took oral paclitaxel and encequidar had higher rates of:
dose reductions because of side effects
severe low white blood cell counts (neutropenia)
Still, women who took oral paclitaxel and encequidar had much lower rates of certain side effects:
8% had neuropathy versus 31% of women who received IV paclitaxel
2% had severe neuropathy versus 15% of women who received IV paclitaxel
48.9% had hair loss versus 62.2% of women who received IV paclitaxel
The researchers noted that women with higher-than-normal liver enzymes or other liver problems had a higher risk of serious infections and that doctors need to be careful when deciding who should be prescribed oral paclitaxel and encequidar.
“[Oral paclitaxel plus encequidar] increased the confirmed tumor response versus IV [paclitaxel], with trends in [progression-free survival] and [overall survival],” the researchers wrote. “Neuropathy was less frequent and severe with [oral paclitaxel plus encequidar]; neutropenic serious infections were increased. Elevated liver enzymes at baseline predispose [oral paclitaxel plus encequidar] patients to early neutropenia and serious infections.”
What this means for you
If you’ve been diagnosed with metastatic breast cancer and are deciding on chemotherapy, the results of this study may sound very promising to you.
Still, there are some things to keep in mind:
The dosing schedule for oral paclitaxel and encequidar means you can’t eat for nine hours each day for three days in a row every week.
This study looked at oral paclitaxel and encequidar versus IV paclitaxel that people received every three weeks. But we know that a weekly dose of IV paclitaxel has the same benefits as the every-three-week dose with fewer side effects. The study’s results only apply to an every-three-week dose of IV paclitaxel. We don’t know how oral paclitaxel and encequidar compares with a weekly dose of IV paclitaxel.
It’s also important to know that the U.S. Food and Drug Administration (FDA) has not yet approved this form of oral paclitaxel and encequidar. If you’re interested in trying it, you may have to ask your doctor to recommend a clinical trial.
Learn more about Clinical Trials.
Written by: Jamie DePolo, senior editor
— Last updated on August 10, 2022, 2:33 PM