Taking a Novel Look at an Established Agent: Malaria Drug Chloroquine Studied in a Preventive Setting for Early DCIS

Anita T. Shaffer
Published Online: Monday, September 17, 2012
Lance A. Liotta, MD, PhD

Lance A. Liotta, MD, PhD, addresses attendees in Miami Beach.

As mammography has grown increasingly sophisticated, the incidence of ductal carcinoma in situ (DCIS) has risen dramatically. Indeed, the diagnosis of DCIS has grown from a relatively rare finding in the 1970s to up to 25% of all breast cancers by 2004, according to the federal Agency for Healthcare Research and Quality.

In recent years, some researchers have expressed concerns about overdiagnosis and overtreatment of DCIS, suggesting that a preventive approach that includes active surveillance might be appropriate for lower-grade lesions.

Taking a different view is Lance A. Liotta, MD, PhD. He believes DCIS lesions, even at low grades, can hold the seeds for invasive cancers.

Liotta has been researching the stages of cancer metastases and tumor cell–extracellular matrix interactions for 40 years. He formerly served as chief of the Laboratory of Pathology at the National Cancer Institute and as a deputy director at the National Institutes of Health. Since 2005, he has served as co-director of the Center for Applied Proteomics and Molecular Medicine at George Mason University in Manassas, Virginia.

His current research focus includes potential uses for chloroquine, an oral small-molecule compound used in the United States to treat patients with malaria since the late 1940s. Based on experiments conducted by his research colleague Virginia Espina, MS, an assistant professor, the team has been exploring chloroquine as a neoadjuvant therapy for DCIS and as a potential means to kill preinvasive breast lesions. The clinician of the research team is Kirsten H. Edmiston, MD, a breast surgeon and medical director of the Inova Breast Care Institute in northern Virginia.

The group is seeking to enroll 90 patients in a clinical trial testing the efficacy of chloroquine in 500-mg/wk and 250-mg/wk doses as a neoadjuvant therapy for DCIS. The trial, listed on the Clinical Trials.gov website (NCT01023477), is sponsored by the US Department of Defense Breast Cancer Research Program (DOD BCRP).

In this interview, Liotta discusses the hypothosis that led to the study and the research thus far into chloroquine.

OncologyLive: What are your views on the management of DCIS?

Liotta:
Some oncologists have said that we shouldn’t even use the word “carcinoma” to describe ductal carcinoma in situ because it’s wrong, it’s too scary, and these are low-risk lesions. But our experimental studies absolutely show that indeed there can be carcinoma cells lurking in those lesions. We found genetically altered cells that look the same as the genetic alterations in invasive cancer cells lurking in human DCIS lesions.

It’s very important for clinicians to understand that a DCIS lesion is not a benign lesion that should be left alone. Something should be done about it because we know that there could be carcinoma cells lurking in there waiting to be unleashed.

We see in our clinical trials that the women who have DCIS seem to be much more eager to get their lesion surgically removed and treated than even the physicians who are used to seeing a very bad outcome with invasive cancer. To the patient, it is just as significant as invasive cancer, and I would say the patient’s concern should be respected.

Please explain the goals of your approach to DCIS.

Our approach is to try to kill the DCIS lesion, kill the premalignant lesion, with one short-term therapy. It’s a new concept in prevention. Imagine a woman coming in to her doctor, getting a short-term therapy with something that’s not very toxic, or not toxic at all, and it kills the premalignant lesions lurking in the breast that we know are to become cancerous. That treatment will clean out all of the potential cancer that could develop in the future for that woman. You might administer this therapy once a year, once every couple of years, or perhaps only once in a woman’s lifetime.

How is this a different concept in prevention?

Standardized prevention trials will require five to 10 years to find out whether your vitamin therapy or your hormonal therapy is going to prevent cancer in that population. By then, science will have changed tremendously and there might be much better strategies with which to treat the patient. We can’t really wait that long to see the result of a prevention trial. We would like to have a trial where we’re treating premalignant lesions.

How is the chloroquine trial structured?

We want to take advantage of the time period between the diagnosis, the biopsy of the original DCIS lesion, and surgery. A woman is told that she has DCIS, that she has a premalignant lesion. She would enroll in our trial, and take chloroquine for 30 days, and then receive the standard-of-care surgical removal of the lesion that she would receive anyway. (Figures 1, 2)

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