• 10/31/2004
  • Ralph W. Moss, Ph.D.
  • Weekly CancerDecisions.com

Herb-derived Drug Fights Head and Neck Cancer

South Carolina doctors have announced that a drug called M4N shrinks inoperable tumors of the head and neck region. Researchers injected M4N directly into the tumors of eight such patients who were not eligible for surgery. According to press releases, they saw evidence that the agent killed the tumors in these patients, all of whom had advanced, otherwise untreatable forms of the disease.

“This study revealed that M4N was generally well-tolerated without direct toxicity,” Terry A. Day, MD, told colleagues at the 6th International Conference on Head and Neck Cancer in Washington, DC, August 10, 2004. Dr. Day is Associate Professor and Director of the Division of Head and Neck Oncology Surgery at the Medical University of South Carolina (MUSC). He is the author of over 150 scientific publications and is president of the Yul Brynner Head & Neck Cancer Foundation. The meeting was sponsored by the American Head and Neck Society (http://www.sic2004.org/).

Dr. Day and his colleagues now plan a larger, Phase II study aimed at showing whether, and at what dosage, the drug really works in this intractable kind of cancer.

American Society of Clinical Oncology Study

Dr. Day’s report followed a related one presented a few months earlier at the American Society of Clinical Oncology (ASCO) convention in New Orleans. At this June 2004 meeting, Frank R. Dunphy, MD, and colleagues from the Duke Comprehensive Cancer Center, Durham, NC (one of the top rated cancer centers in the US) presented the results of their study, in which M4N was injected directly into the tumors of patients with relapsed or refractory (i.e., treatment resistant) head and neck cancer.

Such patients generally have a poor prognosis with only a 10 percent two-year survival. Because M4N has shown activity in laboratory animals when injected intratumorally (i.e., directly into tumors), the same method of administration was used in this trial. The dose was 20 milligrams of the agent per cubic centimeter of tumor, given once weekly for three weeks. Three patients (one woman and two men) were treated. Their ages ranged from 54 to 82, with a median (average) age of 65.

The treatment given at Duke was not without side effects. One patient experienced an episode of heart-block requiring two hospitalizations. Another patient developed a fistula from the trachea to the skin, which necessitated withdrawal from study. All patients experienced pain at the injection site, which was severe enough to require intravenous morphine. (However, as the doctors gained experience with the injection technique, the pain became less severe.)

But the therapeutic results were dramatic: in all three patients “injected tumor volumes were observed to respond by crusting within one week of the first injection, followed within two weeks by necrosis and ulceration.” The two patients who completed the course of three intratumoral injections had “total necrosis of the injected tumor site.” This was certainly quite encouraging in a group with such a dire prognosis. Unfortunately, though, this local dying back of the tumor at the injection site was “followed by disease progression outside the boundaries of the injected tumor volume”.

The Duke authors concluded that “M4N intratumor injection was feasible and showed promising antitumor activity in relapsed-refractory squamous cell cancer.”

Both the Duke University and MUSC groups are participating in an NCI-sponsored clinical trial with BioCure Medical, a small drug company based in the Research Triangle Park of North Carolina.

The description of the trial at the NCI’s clinical trials website (www.clinicaltrials.gov) is as follows:

“The purpose of this study will be to determine the safety and tolerability of intratumoral M4N. Patients suffering from cancer of the head and neck that is recurrent after primary treatment with surgery, radiation therapy, and/or chemotherapy may be eligible. The design is a Phase 1 dose escalation study of M4N administered intratumorally once weekly, initially for three weeks. Dose will be escalated on the starting schedule to a target of 20 mg/cm3 [milligrams per cubic centimeter, ed.] tumor volume and then, new patient cohorts will have their schedule extended to weekly M4N for 4 weeks. Dose escalation will continue, assuming tolerability, so that cohorts will be treated for 6 weeks, and finally, 8 weeks” (www.clinicaltrials.gov).

The Transformation of a Folk Remedy

It seems ironic that the US government now has a financial interest in M4N, since it has done so much over the years to discourage the exploration of chaparral as a cancer treatment. First, the effectiveness of chaparral was denigrated. Then, based on toxicity concerns, it was virtually banned by an agreement between the US Food and Drug Administration (FDA) and the food supplement industry.

So far, however, the chaparral derivative in question does not appear to cause the kind of systemic toxicity that is mentioned in the scientific literature. Initial tests on patients showed that, when it was injected intratumorally, it did not cause the serious liver damage sometimes associated with systemic use of the plant extract.

What is Chaparral?

The term “chaparral” actually refers not to a particular species but to a community of plants, indigenous to the American West and Southwest, that is dominated by evergreen shrubs. Chapparal is also called greasewood, creosote bush or Mediterranean scrubland and grows in dense thickets to a height of four to eight feet. Chaparral is made up of thorny plants including ceanothus, manzanita, chamise, and various evergreen oaks. In most scientific discussions, however, the word usually refers specifically to two particular species of the genus Larrea, L. divaricata and L. tridentata. Some years ago I drove from Phoenix, AZ to San Diego, CA as part of a cross country trip and well remember seeing acre upon acre of chaparral for the length of that 350 mile journey. Despite efforts to ban its sale, chapparal is still available over the Internet and, given its abundance, is very inexpensive. A pound of the stuff sells for under $10!

Chaparral tea is an old Indian and folk remedy for many ailments. It is considered a very effective detoxifier. Chaparral was the main ingredient in the original and controversial “Jason Winters tea” formula. It has also been used in many “black ointment” salves, some of which are associated with toxic skin reactions.

In his monumental study, Plants in Use Against Cancer, the late Jonathan Hartwell, PhD, of the National Cancer Institute, reported the ethnobotanical use of chaparral against stomach cancer. Chaparral remains a popular remedy for a wide variety of illnesses. It was propounded as an American remedy for cancer over half a century ago and is used for the same purpose in at least one other country, Argentina.