Intrathecal chemotherapy: 10 questions, answered
February 19, 2026
Leptomeningeal disease (LMD) occurs when microscopic cancer cells spread to the fluid surrounding the brain and spinal cord. These cells may come from a solid tumor, such as breast cancer, lung cancer, or melanoma, or from a blood-based cancer, such as leukemia or lymphoma.
In solid tumors, leptomeningeal disease is often a sign that the cancer is becoming more aggressive, and it can be really difficult to treat. That’s why we take an approach called intrathecal chemotherapy.
Read on to learn how intrathecal chemotherapy works and who makes a good candidate for it.
Why is intrathecal chemotherapy used?
The blood-brain barrier is a natural defense that protects the central nervous system from disease and infection. Normally, it allows essential things to get through — such as oxygen and nutrients — and keeps everything else out. This helps maintain a stable environment for the brain and spine. Unfortunately, it’s not perfect. So, sometimes, cancer cells sneak through anyway.
Most cancer medications don’t cross the blood-brain barrier, either. That means oral chemotherapies and other drugs administered through an IV can’t get to where they need to go. This is one reason treating leptomeningeal disease can be a challenge — and where intrathecal chemotherapy comes in.
How does intrathecal chemotherapy work?
Intrathecal chemotherapy bypasses the blood-brain barrier entirely by injecting drugs directly into the cerebrospinal fluid. It is typically administered in one of two ways:
- An Ommaya reservoir: An injection into a small, dome-shaped port installed under the scalp, which is attached to a catheter in a ventricle of the brain
- A lumbar puncture: An injection delivered into the spinal fluid through the lower back
At MD Anderson, an Ommaya reservoir is almost always used for leptomeningeal disease due to solid tumors.
Does intrathecal chemotherapy hurt?
When it’s administered through an Ommaya reservoir, it’s no different from the little prick you might feel when clinical staff access the port on your chest. We use local anesthesia to keep patients comfortable during lumbar punctures.
How long will I need to receive intrathecal chemotherapy?
Typically, for as long as it’s still working and is tolerable. Patients usually start by receiving it twice a week for eight weeks. Then, we restage the cancer to see if treatment is working.
If treatment is working, we might consider increasing the time between doses. If it’s not, we might try something else.
What are the side effects of intrathecal chemotherapy?
Chemical meningitis is probably the most common side effect of intrathecal chemotherapy. That causes headaches, neck pain and sometimes nausea. We typically treat it with steroids.
Fatigue is also pretty common. But you won’t lose your hair from intrathecal chemotherapy, though part of your head might be shaven to make room for the reservoir. For the right patient, it is quite well-tolerated.
The most common side effect of a lumbar puncture is a mild headache.
Which patients make the best candidates for intrathecal chemotherapy?
Intrathecal chemotherapy is usually best for patients:
- Whose LMD volume is relatively low and not “bulky”
- Whose primary cancer is well-controlled
- Who function well on a day-to-day basis
- Who live close by the facility that offers it
The first two criteria apply because intrathecal chemotherapy doesn’t typically penetrate beyond 2-3 millimeters. So, if your LMD is more “nodular,” then intrathecal chemotherapy is not going to be as effective. It works best when used to treat free-floating cells in the spinal fluid, or on very thin coatings of cancer cells along the lining covering the brain and spine.
The second two apply because intrathecal chemotherapy’s benefits are typically modest. Although some patients continue it for years, survival is often measured in months. So, if you’re already very frail and you live three states away, having to travel back and forth frequently might not be in your best interest.
Which drugs are typically used with intrathecal chemotherapy?
The big three are cytarabine, methotrexate and topotecan.
Which cancers is intrathecal chemotherapy used most often to treat?
Breast cancer that has spread to the brain is probably the most common in terms of volume, along with lung cancer and melanoma.
What are the risks and benefits of intrathecal chemotherapy?
One of the biggest benefits is that it doesn’t interfere with other systemic therapies, because it largely stays within that fluid compartment. So, we can typically give it to you alongside any other drugs you are receiving.
Risks include infection at the reservoir or injection site, which is very, very rare, and myelopathy, or irritation of the nerves in the spinal cord, which is extremely rare. The latter can cause back pain, weakness and sensory impairment.
What are the latest advances in intrathecal chemotherapy?
I’m actually doing less intrathecal chemotherapy today than I was a few years ago. The reason is that there have been so many advances in radiation and systemic therapies that can cross the blood/brain barrier. This is especially true for HER2 positive breast cancers and non-small cell lung cancers that have an EGFR mutation or ALK mutation.
So, one of the biggest questions now is sequencing: which treatment do we try first?
However, there is a still an important role for intrathecal therapy to play, and this is an active area of research. For instance, my colleague, Isabella Glitza Oliva, M.D, Ph.D., led a study not too long ago involving an immunotherapy agent that she administered both intravenously and intrathecally. She used it to treat patients with metastatic melanoma, and the results show promise.
Barbara O’Brien, M.D., is a neuro-oncologist at MD Anderson and the director of the Dept of Neuro-Oncology LMD Program.
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Key takeaways
- Intrathecal chemotherapy bypasses the blood-brain barrier by injecting drugs directly into the cerebrospinal fluid.
- Since it doesn’t interfere with systemic therapies, intrathecal chemotherapy can often be given alongside other cancer-fighting medications.
- Intrathecal chemotherapy works best against free-floating cells in the spinal fluid, or on thin coatings of cancer cells on the linings covering the brain and spine.
For the right patient, it is quite well-tolerated.
Barbara O'Brien, M.D.
Physician