Novel Turmeric Derivative Drug Shows Promise in Head and Neck Cancer

MONTREAL – An investigational drug derived from turmeric (Curcuma longa) appeared to have activity in patients being evaluated for head and neck cancer therapy, at least in an early phase trial.

All nine oropharyngeal squamous cell carcinoma patients treated in the phase II trial had their disease under control after 4 to 6 weeks of neoadjuvant treatment with the agent, dubbed APG-157, an interim analysis showed.

“No subject given APG-157 has had recurrence or progression from 1 month to 12 months following post-curative intent therapy,” Marilene Wang, MD, of the David Geffen School of Medicine at the University of California Los Angeles, reported here at the annual meeting of the American Head & Neck Society.

There also were no drug-related adverse events, Wang said in her oral presentation of the interim findings.

Wang explained that APG-157 is a first-in-class combination molecule containing C. longa that is formulated into a hydrogel pastille that dissolves under the tongue. Each pastille contains 100 mg of the drug, and patients are dosed with 300 to 600 mg of APG-157 each day.

“This is not a targeted agent,” Wang said. Rather, the agent’s multiple molecules are believed to work to arrest cancer stem cells with the aim of preventing recurrence. They can selectively induce cancer cells to undergo apoptosis, activate the patient’s immune system, downregulate the inflammation cascade, and restore oral microbiome homeostasis, she said.

Curcumin is a bright yellow compound produced by plants of the C. longa species, and is the principal curcuminoid of turmeric, itself a member of the ginger family, Zingiberaceae. The principal molecule in APG-157 is zinflavonoid.

Wang said her laboratory has been studying curcumin and its anti-cancer properties for many years. “We began with cell line and animal model data and found significant suppressive effect of curcumin on cancer cell growth,” she said. “Our initial pilot study in human patients was done in oral cavity patients. Just one hour after chewing curcumin, we found significant reduction in the inflammatory cytokines in the saliva.”

However, Wang noted, “while curcumin alone appears promising for treatment of cancer, it’s limited by its poor mucosal absorption and limited bioavailability. A more effective approach and philosophy used in botanical medicine is to combine multiple molecules to work synergistically for an optimal pharmacological and clinical response. APG-157 was designed with this in mind and it contains all of the natural polyphenols of curcumin.”

In commenting on the study, co-moderator John Gleysteen, MD, of the University of Tennessee Health Science Center in Memphis, told MedPage Today that it is still “really early days” for the compound being studied.

Nevertheless, “it’s interesting in that it’s cool to use a novel combination of molecules that comes from something very natural to treat cancer. Patients are usually more receptive to something like that. But you can’t just buy turmeric and take it,” he cautioned.

“Only about half the patients responded and only one or two actually responded well, so it’s way too early to know who’s going to respond to it, how durable the response would be, and then how could you potentially integrate that into an overall treatment plan? It’s still just the beginning, but it’s got to start somewhere,” Gleysteen said.

The phase II study is planned to have a total of 24 patients dosed 4 to 6 weeks during the time period between the diagnosis and the definitive treatment with either surgery or chemoradiation. Wang said participants were included if they had biopsy-proven oropharyngeal squamous cell carcinoma. Patients with all stages of non-metastatic cancer were eligible.

Patients were excluded if their treatment was available or they were scheduled to start definitive curative treatment in less than 4 weeks. “We didn’t want to delay treatment by putting them in this new adjuvant treatment trial,” she said.

In the interim report, eight of the nine patients were treated with APG-157 for 4 weeks; one patient was treated for 6 weeks before definitive therapy.

One patient experienced a 3.6% increase in tumor progression – still considered within the range of disease control — during the lead-in to definitive treatment. Four additional patients showed no change in tumor size during the neoadjuvant therapy period. Two had minor responses based on RECIST criteria. One patient had a partial response in which tumor shrinkage of 31.3% was observed.

One person achieved 100% tumor shrinkage.

Wang said the next step in the development of APG-137 is a phase IIb study, which will enroll up to 120 patients.