Refractory Cancer: What It Is and How It Is Treated

Medically Reviewed By: Ann S. LaCasce, MD, MMSc
  • Refractory cancer refers to a type of disease that does not respond to treatment.
  • The term “refractory” can also apply to disease that resists a specific type of treatment.
  • For patients with refractory disease, treatment options include receiving a second- or third-line treatment, or participating in clinical trials.

What does “refractory” mean medically?

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 to initial therapy 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 Cancer Care Fellowship Program in Hematology/Medical Oncology.

What are the treatment options for patients with refractory disease?

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 CAR-T cell therapy.

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 after two prior lines of chemotherapy. Two recent studies, which led to expanding the FDA approval, demonstrated that CAR-T cell therapy is more effective than second line chemotherapy followed by stem cell transplant in patients who are refractory to initial therapy or have relapsed within one year. 

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.

How does cancer become refractory?

That really depends on the type of cancer. Tumor cells can be naturally resistant to a particular form of treatment, or they may change over time to develop that resistance. In addition, the mechanisms by which tumor cells outsmart certain cancer treatments can be quite complex biologically. Some of these resistance mechanisms are well understood, but others are not yet clear.

What is the difference between relapsed cancer and refractory cancer?

Relapsed cancer means the disease has returned after being in remission. Refractory cancer means the tumor is not responding to the most recent treatment. Some tumors can be relapsed and refractory — meaning the cancer has returned and it is not responding to the particular treatment being used.

What are the symptoms of refractory cancer?

The symptoms can vary widely and often depend on the specific type of cancer (for example, breast, lung, pancreatic, etc.) and where in the body the tumor is located. Some forms of refractory cancer can have no symptoms whereas others can be quite severe.

About the Medical Reviewer

Ann S. LaCasce, MD, MMSc

Ann LaCasce, MD, MMSc, Associate Professor of Medicine, is a lymphoma specialist and is the Director of the Dana-Farber/Mass General Brigham Fellowship in Hematology/Oncology.  She serves on the Alliance Lymphoma Committee, the National Cancer Comprehensive Lymphoma Guidelines Panel and the Lymphoma Research Foundation’s Scientific Advisory Committee.  

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