Mistletoe extract shows promise in phase 1 study of patients with advanced cancer
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In a phase 1 trial of mistletoe extract for patients with cancer, researchers at Johns Hopkins Kimmel Cancer Center found the therapy to not only be safe but also potentially beneficial to quality of life.
“Mistletoe extract is a complementary medicine that differs from other therapies in that the literature suggests it may improve quality of life,” Channing J. Paller, MD, associate professor of oncology at Kimmel Cancer Center, told Healio. “We were really excited to explore it as the first phase 1 trial of an intravenous compound under an investigational new drug application in the United States.”
At median follow-up of 15.3 weeks, Paller and colleagues found the maximum tolerated IV dose of mistletoe extract to be 600 mg. Thirteen patients (61.9%) experienced treatment-related adverse events, the most common being fatigue (28.6%), nausea (9.5%) and chills (9.5%). Three patients (14.8%) experienced grade 3 or higher treatment-related adverse events. Five patients who had undergone one to six previous treatments had stable disease, and three patients had decreases in baseline target lesions.
Mistletoe extract achieved a 23.8% disease control rate.
Paller spoke with Healio about the therapeutic properties of mistletoe extract, her study’s findings regarding safety and dosage, and her career-long interest in improving quality of life for patients with cancer.
Healio: How is mistletoe extract used in treating patients with cancer?
Paller: Mistletoe has been commonly used for many years, mostly in Europe. It’s usually administered subcutaneously, but sometimes intravenously. It contains viscotoxins and mistletoe lectins as its active components. These have immunomodulatory, cytotoxic and anti-inflammatory effects.
Healio: Why did you study intravenous administration of mistletoe in your study?
Paller: This originally all started with a patient named Ivelisse Page, who was a patient of Luis Diaz, MD. She had metastatic colon cancer that spread to her liver, and both the colon and liver were removed. She made the decision not to receive chemotherapy. We were really impressed by her long-term remission. They brought me in because my long-term passion, in addition to precision medicine based on genetics, is improving quality and quantity of life. I had been studying many natural products along the way — from Muscadine grape skin and pomegranate to IV vitamin C — and some of those papers will be coming out in the next few years. So, I really took it upon myself to look at what is going on in naturopathic medicine.
Healio: What other research have you conducted in this area?
Paller: Patients were coming to me and asking, “Can I take antioxidants to help me feel better and recover from chemotherapy? Can I take IV vitamin C, IV mistletoe or subcutaneous mistletoe to help with my therapy? Do these treatments help? Should I take these during treatment, or after?” So, I have really taken the lead from my patients. Just because there is no drug company backing these drugs with a patent does not mean we should not be studying these compounds rigorously. People think they may help, and we need to look at them. So, one by one, I’m slowly chipping away and studying these compounds.
I was brought into the phase 1 IV mistletoe trial because I had done a lot of the regulatory work for investigational new drug applications for these other compounds. It was a tremendous effort and a phenomenal team.
Healio: How was the trial designed and what did you find?
Paller: We studied Helixor-M. The M stands for Malus and indicates that the mistletoe plant was originally harvested from the Malus apple tree. We designed a small phase 1 trial, employing a traditional 3 + 3 design. We escalated dosage starting at 150 mg and 300 mg, then 600 and 900 mg. We found 600 mg to be our safe dose or maximum tolerated dose to proceed with the phase 2 trial. At the median follow-up duration of about 15.3 weeks, stable disease was observed in five patients, and it lasted for months. In two patients, it actually lasted 6 months, and in three patients, the tumor decreased in size. It didn’t meet partial response criteria — the maximal shrinkage was 27%. This is very impressive for advanced or treatment-resistant cancers. The patients had all had multiple lines of therapy before coming on to this trial. So, what we’re really excited about is what if we introduced this earlier? To me, that is the most impressive finding — the pleasant surprise that people had improvement in quality of life, even in a phase 1 trial of patients with advanced disease.
Healio: How did you assess quality of life, and what did you find?
Paller: We had validated questionnaires. That’s not something you normally do in phase 1 trials. We found that the people who had a response or had stable disease had the best improvements in quality of life. The fact that it was even happening was tremendous. So, even though we haven’t finalized what will be next in terms of phase 2, we are looking at combining it with standard-of-care therapies and looking at both efficacy and quality of life. If patients can tolerate a standard therapy longer, they can potentially stay on it longer and live longer with better quality of life.
Healio: Is there anything else you think would be important to mention on this topic?
Paller: I want to send out a heartfelt thank you to the patients who participated in this trial and their families, and to the entire medical team. We screened close to 100 patients and found 21 who were eligible. They spent 3 hours, three times a week with the team. That’s a lot of time away from their families. I told the two patients who were stable at 6 months to go be with their families. We moved them to subcutaneous administration so they could receive treatment at home. I told them, “We found a safe dose. You’ve done your duty for society — thank you for being a clinical trial hero.”
For more information:
Channing J. Paller, MD, can be reached at Johns Hopkins University, 8600 Old Georgetown Road, Bethesda, MD 20814; Twitter: @Cpaller.
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