Anthony P. Conley, MD: The selection of chemotherapy for your patient will oftentimes depend upon a variety of factors, such as the pathologic diagnosis, the ECOG performance status, as well as organ function. We generally recommend doxorubicin-based therapies, first, based on the available body of evidence that suggests both its efficacy and its safety. While doxorubicin can be associated with cardiotoxicity and bone marrow abnormalities, we need to keep in mind that it is a very effective medication. And, when combined with medicines such as olaratumab, it has been shown to improve overall survival, compared to doxorubicin, alone.
Some clinicians may wonder about the use of other drugs, such as ifosfamide. Ifosfamide is also an excellent medication, but it is cumbersome in terms of its administration. And its side effect profile is significantly more notable, compared to medicines such as olaratumab. There have not been any direct comparisons of doxorubicin plus ifosfamide versus doxorubicin/olaratumab. But we do know that the side effect profiles are generally different. When we think about using medicines such as doxorubicin plus ifosfamide, we need to consider the safety, first, for the patient.
However, we do know that there have been high response rates reported with medicines such as doxorubicin and ifosfamide. So, if you have a patient with disease that needs chemical debulking in a relatively short period of time, doublet therapies are generally preferred, as compared to any single agents. With doxorubicin and olaratumab, we also see an increased response rate compared to doxorubicin, alone. And so, this may improve the patient’s chances of having an improvement in both their symptoms and quality of life.
Sometimes, clinicians may have concerns about the use of doxorubicin because of cardiotoxicity. But in general, if you have a patient who has a normal echocardiogram, whose cardiovascular risk factors are known and are controlled for, I think it’s very reasonable to provide them the best possible care that we know of.
While gemcitabine/docetaxel is a reasonable combination therapy, I typically select these combinations for specific subtypes of sarcoma, such as uterine leiomyosarcomas or, sometimes, undifferentiated pleomorphic sarcomas, which have been known to have increased responsiveness to therapy when compared to other sarcoma subtypes.
Importantly, there has not been any direct comparison of doxorubicin and olaratumab against gemcitabine and docetaxel. So, it isn’t known which of these regimens would be superior. But there have been previous European studies that have clearly shown that doxorubicin, as a single agent, favored comparably to gemcitabine and docetaxel.
When I select doxorubicin and olaratumab for the treatment of advanced metastatic sarcoma for a patient, I generally try to make sure that the patient understands the side effects. We do this by providing them with both a paper form of information with the listed side effects, along with an actual teaching class where the patient has the opportunity to interact with our nursing staff, nurse practitioners, and physician assistants.
I usually try to make sure that I ask the patients questions to determine whether they do understand what the side effect profile is. There are certain things that we need to be aware of. Because olaratumab, in combination with doxorubicin, as compared to doxorubicin, alone, was associated with a higher rate of neutropenia, it’s important that patients be aware of what needs to be done to hopefully prevent infection.
To begin with, it is recommended to use growth factor support. This will decrease the likelihood of having a febrile neutropenic event and, also, having a hospitalization that is related to infectious complications from this.
We generally recommend that patients have laboratory checks several times throughout the chemotherapy cycle. At our center, we generally recommend 2 to 3 times per week, depending on the patient’s individual needs. This way, we’re able to monitor how quickly the patient becomes neutropenic, and decide whether or not we need to intervene for side effects such as anemia, thrombocytopenia, or for electrolyte abnormalities.
The other thing that I think is important for a patient to be aware of is infusion reactions can occur with medicines such as olaratumab. It’s important that both the pharmacist and treating clinician be aware that supportive medicines, at the time of olaratumab administration, should be performed to prevent infusion-related reactions.
Transcript Edited for Clarity