The word “refractory” in general use means stubborn or intractable, and in medicine it is specifically applied to disease that does not respond to treatment. Refractory cancer refers to cancer that may be resistant at the beginning of treatment, or becomes resistant during treatment.
“We would consider disease refractory if doesn’t respond at all or responds but starts to grow in a very short time frame,” explains Ann LaCasce, MD, MMSc, a physician in the Adult Lymphoma Program at Dana-Farber and director of the Dana-Farber/Partners CancerCare Fellowship Program in Hematology/Medical Oncology.
When a patient’s disease is or becomes refractory, the next step may be to try another form of treatment — called a second- or third-line treatment — or to enroll the patient in a clinical trial.
For example, when a patient has refractory non-Hodgkin lymphoma (NHL), doctors may prescribe second-line treatment such as combinations of several chemotherapy agents. One such regimen is R-ICE (rituximab, ifosfamide, carboplatin, and etoposide). Sometimes, a second-line treatment for non-Hodgkin lymphoma is followed by a stem-cell transplant.
The meaning of refractory may be somewhat different depending on the context. For example, the groundbreaking treatment known as CAR T-cell therapy was approved in October 2017 for adults with refractory aggressive B cell non-Hodgkin lymphoma. In this setting, the lymphoma must be refractory to two previous lines of treatment for the patient to receive CAR T-cell therapy.
The term “refractory” can also apply to disease that resists a specific treatment. For example, hormone-refractory prostate cancer refers to disease that initially responds to drugs that block male hormones from fueling the cancer, but eventually the tumor becomes refractory to treatment.