End stage pancreatic cancer

The Clinical Trial

During the early 1990s, the National Cancer Institute began evaluating unconventional cancer therapies in the hope of identifying those with potential for further study.

In 1993, Dr. Michael Friedman, as sociate director of the institute's Cancer Therapy Evaluation Program in Bethesda, Md., heard of unorthodox work being done by Dr. Nicholas Gonzalez and invited him to Washington to present a "best case" series. Based on the presentation, Dr. Friedman then suggested that Dr. Gonzalez conduct a pilot study of his treatment in patients with advanced adenocarcinoma of the pancreas.

The end point of the study would be survival.

The results of this pilot study were published in 1999. Of the 11 patients included in the study, 9 had survived at least 1 year, 5 had survived for 2 years, and 4 lived for 3 years. Two of the patients remained alive 4 years later.

In contrast, the median survival for patients with inoperable pancreatic cancer who undergo chemotherapy is 51/2 months (J. Clin. Oncol. 15[6]: 2403-13, 1997).

The response to this difference in survival is NCI-V99-1538--a $1.4 mil lion trial that is being sponsored by the National Institutes of Health's National Center for Alternative and Complementary Medicine and being conducted at Columbia University's Herbert Irving Comprehensive Cancer Care Center.

The trial compares standard chemotherapy for advanced pancreatic cancer to Dr. Gonzalez's unorthodox metabolic regimen of porcine pancreatic enzymes, diet, and detoxification procedures.

Origin of the Protocol

Dr. Gonzalez planned on having an academic career as a cancer researcher at Memorial Sloan-Kettering Cancer Center in New York. But in 1981, as a second-year medical student at Cornell University, also in New York, he began a research project under the guidance of Dr. Robert Goode, then president of Sloan-Kettering. The project investigated the work of Texas orthodontist William Kelley, who claimed to get extraordinary results treating terminal cancer patients with a complex nutritional regimen.

Dr. Kelley had been diagnosed with pancreatic cancer and chose to treat himself based on some experimental approaches that had been investigated-and abandoned-in the early 20th century.

His approach was based on the findings of Dr. James Beard, a Scottish embryologist. Dr. Beard had observed that placental growth, which he likened to the growth of tumor cells, ceased once the fetal pancreas began secreting the enzymes it would ultimately need for the digestion of food. Dr. Beard postulated that the pancreatic enzymes were responsible for limiting the rapid growth of the developing placenta and also might be able to control the unchecked growth of tumor cells.

Some initial efforts were made to test this hypothesis. Dr. Beard sought to create interest in his work via the lecture circuit but had little success. Marie Curie's radiation treatments had begun to dominate cancer care and would continue to do so until radiologists began dying from overexposure.

By the time that Dr. James Beard died in 1923, his pancreatic enzyme theory had been relegated to near obscurity. It remained on the fringe through the sub sequent decades in which chemotherapy was introduced and systematized. Then Dr. Kelley revived the pancreatic enzyme approach, and Dr. Gonzalez became interested.

During a fellowship in immunology, Dr. Gonzalez conducted a retrospective review of 1,306 patients treated by Dr. Kelley and interviewed patients who had survived many years. Dr. Gonzalez became convinced of the potential benefits of a metabolic approach to cancer treatment.

In 1987, he set up a private practice in New York City, where he began treating patients with a modified version of Dr. Kelley's program. He struggled to gain acceptance for his work.

Criticisms of the Trial

Dr. Gonzalez has not been without his critics, who dismiss his approach as contrary to contemporary under standing of the pathogenesis of cancer. But patients have been enthusiastic.

The phase III trial was originally designed to be a randomized comparison of the Gonzalez regimen and standard chemotherapy with gemcitabine.

"But out of the first 260 calls to Columbia about the phase III trial, 257 patients said they would be unwilling to participate if they might be randomized to the chemotherapy arm," Dr. Gonzalez told this newspaper.

The NIH subsequently permitted the protocol to be changed so that patients themselves can choose either chemotherapy or the Gonzalez treatment.

The study began (6 months ago, and it has been projected that 72-90 patients will be enrolled over a 3-year period. The entry criteria are strict: All patients must have histo-logically confirmed stage II-IV adenocarcinoma of the pancreas diagnosed within the previous 8 weeks and can not have undergone any prior radiation therapy or chemotherapy.

Thus far, seven patients have entered Dr. Gonzalez's program. One decided to stop treatment and died several weeks later, but the other six remain alive.

"It's a small number and a short time, but I think at least some of these patients are going to do fine," he said.

"I don't understand my critics," Dr. Gonzalez said in an interview

"I know that what I do is controversial, but I'm trying to do the most exacting science, out in the open. We're doing everything according to the standards of academic science," he said, adding that patient selection and monitoring are being done by Columbia oncologists.