Is Hydroxychloroquine an Effective Cancer Treatment?

Hydroxychloroquine, a decades-old drug for malaria, lupus and rheumatoid arthritis, is not an established cancer treatment, though researchers are studying it seriously. They aren’t testing it as a cure on its own. The idea is that it might help chemotherapy, radiation or other cancer drugs work better.¹ The early promise in lab animals has been only partly borne out in patients, so it remains experimental.

What the Best Human Trials Show So Far

The largest comparison so far was in people with pancreatic cancer that had spread. Patients received standard chemotherapy with or without hydroxychloroquine at 600 mg twice a day.² After one year, 41% of the hydroxychloroquine group were alive, versus 49% of those on chemotherapy alone.³ Typical survival was about 11 months with the drug and 12 months without it.⁴ Adding hydroxychloroquine did not help people live longer in this setting, and the researchers did not recommend it for routine use.⁵

Tumors did shrink more often, though. They shrank noticeably in 38% of patients given hydroxychloroquine, compared with 21% without it.⁶ A separate trial looked at people whose pancreatic tumors might be removable. Adding the drug to two rounds of chemotherapy before surgery led to more than half of the tumor cells being destroyed in 56% of patients, versus 10% without it.⁷ Survival after surgery was similar in both groups, about 36 versus 32 months, a gap too small to be sure of.⁸

Shrinkage and survival can point in different directions because a “response” usually just means a tumor got smaller by a set amount on a scan. Tumors can shrink and then regrow, so a good early scan may not last long enough to add months of life. Oncologists weigh survival most heavily when deciding whether a drug becomes standard care.

For someone with spread-out pancreatic cancer, the largest trial gives no reason to ask for hydroxychloroquine to be added to standard chemotherapy outside a study. The pre-surgery finding is the more hopeful thread, but larger studies would be needed to learn whether it helps people live longer. If your care team thinks you fit such a study, a clinical trial is the proper place to receive the drug, with monitoring built in.

How Hydroxychloroquine Is Supposed to Fight Cancer

Cells have a recycling system that breaks down worn-out parts for reuse. Many tumors lean on it to survive the stress of chemotherapy and radiation. Blocking it could leave cancer cells more vulnerable to those treatments.⁹ The drug does this mainly by stopping the cell’s waste-carrying bubbles from merging with the compartments that digest them.¹⁰ Chloroquine and hydroxychloroquine are the only already-approved drugs that block this process, which is why they’re the ones used in trials.¹¹

Recycling may not be the whole story. In animal studies, chloroquine made tumor blood vessels more normal, improving blood flow and helping chemotherapy reach the tumor.¹² It may also switch immune cells inside tumors from ones that help the cancer to ones that attack it.¹³ In mice, adding hydroxychloroquine to an immunotherapy drug slowed head and neck tumor growth by 80%.¹⁴

Mouse results often fail to carry over to people. Mice can be given doses and drug combinations that people could not tolerate, and their tumors are more uniform than human cancers. The 80% figure is a reason to run human trials, not evidence of benefit.

That’s also why the drug is tested as an add-on. Cancer cells lean hardest on their recycling system when another treatment is attacking them, so blocking it matters most in that moment. On its own, hydroxychloroquine is not expected to kill much cancer, since cells that aren’t under stress can often cope without that backup. Almost every trial pairs it with chemotherapy, radiation or a targeted drug.

Cancers Where It Has Shown Promise

Most of the encouraging evidence comes from early trials. These are small and mainly check safety, and without a comparison group they can’t prove a drug added anything.

In advanced melanoma with a BRAF gene change, combining two targeted drugs with hydroxychloroquine shrank tumors in 85% of patients.¹⁵ In 41%, the visible cancer disappeared completely, and typical survival was about 26 months.¹⁶ Because there was no comparison group, it’s unclear how much the hydroxychloroquine added to the two targeted drugs.

In newly diagnosed glioblastoma, an aggressive brain tumor, adding hydroxychloroquine to radiation and chemotherapy gave typical survival of about 16 months.¹⁷ A chloroquine trial found 16 months as well, longer for people whose tumors had certain gene features.¹⁸ The highest tolerable dose, 600 mg a day, often wasn’t enough to fully block the recycling system.¹⁹

In spread-out colorectal cancer, hydroxychloroquine with standard chemotherapy shrank tumors in 68% of patients.²⁰ Paired with a different drug combination, though, it showed no benefit at all.²¹ In a small breast cancer trial, tumors held steady in most of 14 patients.²² Cancers also differ in how much they depend on cell recycling, and doctors don’t yet have a reliable test to tell which patients are likely to respond.

Side Effects at Cancer-Trial Doses

Trials often use 400 to 600 mg twice a day, far more than the usual 200 to 400 mg a day for lupus or arthritis. At these high doses, damage to the retina, the light-sensing layer at the back of the eye, can begin within 1 to 2 years.²³ Early retinal changes may cause no symptoms, so people can feel and see normally while damage builds.²⁴

Monitoring starts with a baseline eye exam before the first dose, so later changes can be compared with how the retina looked at the outset. It usually includes retinal imaging, such as an OCT scan that takes detailed cross-section pictures of the retina, and visual field tests that map blind spots. Checks are repeated while on the drug, and more often at cancer-trial doses than at arthritis doses. Any blurring, trouble reading or flashes of light should be reported promptly, not left until the next scheduled visit.

The drug can also cause stomach upset and, rarely, serious heart rhythm problems. In mice, it disrupted cell structures in the kidney and intestine.²⁵ Taking it on your own is risky: the drug can interact with heart medicines and some cancer drugs, so your oncologist needs to know about every pill you take.

Should You Ask Your Oncologist About It

Because the drug’s benefit is unproven, a clinical trial is the main way to get it with proper monitoring. You can search for open trials at ClinicalTrials.gov using your cancer type and “hydroxychloroquine.”

Useful questions for your oncologist: Has hydroxychloroquine been tested in my specific cancer type and alongside the treatment I’m getting? Results in other settings may not apply. Do any open trials near me include it, and would I qualify? Could it interact with my current medicines, including any heart drugs? What would eye and heart monitoring look like, and who would arrange it?

Being cheap and approved doesn’t make it proven for cancer. That price is part of why large trials are scarce. Its safety record comes from other uses, at lower doses, and only a few large comparison trials have been done for cancer.

Hydroxychloroquine is off-patent, so drug companies have little financial reason to fund them.²⁶ Researchers are developing stronger, more targeted versions and delivery methods to overcome its limits.²⁷²⁸