The Phase III Gonzalez Protocol Trial, Questions & Answers

http://nccam.nih.gov/news/19972000/121599.htm

Questions & Answers:
The Phase III Gonzalez Protocol Trial

NIH News Release
National Institutes of Health

National Center for Complementary and Alternative Medicine (NCCAM)
National Cancer Institute (NCI)

Updated November 2005

On the basis of promising pilot study data, the National Center for Complementary and Alternative Medicine (NCCAM) and the National Cancer Institute (NCI) funded a clinical trial comparing gemcitabine-containing chemotherapy to an alternative cancer treatment consisting of proteolytic enzyme therapy with nutritional support (known as the Gonzalez regimen) to treat patients with advanced pancreatic cancer. The study is being conducted at the Herbert Irving Comprehensive Cancer Center at Columbia University and affiliated sites in New York City.

In October 2005, Columbia University closed the study to new enrollment after the Data and Safety Monitoring Board unanimously agreed that sufficient numbers of subjects had been enrolled to permit the study to achieve the predetermined research endpoints. Patients already enrolled on the trial will continue to be followed until the study is complete.

Once the data from all the patients in the study are complete, the investigators will analyze and report their findings. Final results are expected within 2 years.

1. How does the Phase III Gonzalez protocol trial work?

The trial was initially set up to randomize 90 pancreatic cancer patients to one of two treatment arms. The first arm was the standard treatment for advanced pancreatic cancer that cannot be removed surgically. It involved a drug called gemcitabine given intravenously for 30 minutes once weekly for 7 weeks. The second arm was called the nutritional arm in which patients received pancreatic enzymes orally every 4 hours and at mealtime for 16 days. Patients also received up to 150 pills daily in the form of dietary supplements such as magnesium citrate, papaya plus, vitamins, minerals, trace elements, and animal glandular products. Coffee enemas were also administered daily.

Only a few patients enrolled in the randomized trial. The design of the trial is now changing to a single-armed, non-randomized case-cohort study where patients will only be enrolled in what was the nutritional arm. Researchers plan to compare patients on the Gonzalez regimen to a concurrently accrued group of patients being treated with gemcitabine, although such comparisons are known to be difficult because patients selected for the newer or older treatments may not be entirely comparable.

2. Why was the study developed?

Nicholas Gonzalez, a New York physician, submitted selected results of treatment with his nutritional therapy to the National Cancer Institute (NCI) in 1993. He had treated 11 patients with diverse cancers but the benefits from his therapy were not clear-cut. NCI felt that in order to determine whether or not the treatment was beneficial, a prospective study should be undertaken. Dr. Gonzalez chose to study pancreatic cancer patients since he had an impression that patients with this type of cancer benefited from this therapy. Five of 11 patients in the initial series, which was sponsored by the Nestle Corporation, survived for 2 years or more and the results were published this past spring in the journal, Nutrition and Cancer [33(2):117-124].

Patients on the Gonzalez regimen lived an average of 17 and a half months, which is nearly three times the usual survival period for patients with advanced pancreatic cancer. The patients who received his therapy may have had less aggressive tumors or may have been in better condition at the beginning of the study. However, observed survival seen in this series was sufficient for a group at Columbia-Presbyterian Hospital in conjunction with the National Institutes of Health (NIH) to undertake a prospective, randomized Phase III trial.

3. What kinds of pancreatic cancer patients are being enrolled in this trial?

Patients with stage II, III, and IV pancreatic cancers are being enrolled. Patients must be between 18 and 65 years of age, have had no previous chemotherapy or radiation therapy, and not have had surgery at least a week before enrolling.

4. Why did Gonzalez use pancreatic enzymes to fight pancreatic cancer?

It is known that chemotherapy can stop tumor cells from dividing so that they cease growing or die. Gonzalez felt that pancreatic enzymes could act like chemotherapy and kill cancer cells. Gonzalez based some of his protocol on theories derived from turn-of-the-century studies from the University of Edinburgh that showed that pancreatic enzymes had cancer-killing properties. Gonzalez's regimen is derived primarily from his experience working with William Kelley, D.D.S., who apparently developed this treatment approach and reported it in a book called "One Answer to Cancer."

5. Who is supporting the Gonzalez protocol trial and what is the extent of the support?

The $1.4 million provided for this 5-year clinical study is funded entirely by NIH's National Center for Complementary and Alternative Medicine (NCCAM). $48,000 of these monies was expended in the first year and $196,000 has been approved as carryover funding for the second year. The initial mechanism of support is through an existing grant supplement with one of the NCI's Comprehensive Cancer Centers at Columbia-Presbyterian University in New York. The funding mechanism was determined during the period that the NCCAM was originally a coordinating office (formerly called the Office of Alternative Medicine) and did not have the ability to directly fund its own grants. In addition, this funding mechanism was the most expedient option available at the time for providing the research infrastructure and clinical expertise necessary to oversee this type of study. The NCCAM and NCI continue to collaborate on this project to ensure that this study is conducted with scientific rigor and to assist trial researchers with making their trial accessible to the public. Information on this trial is currently available from NCI's clinical trials database.

6. What are the odds of living with pancreatic cancer?

Cancer of the pancreas is rarely curable. It is the fifth leading cause of cancer death in the United States. The highest survival rate occurs if the tumor is truly localized to the pancreas. Unfortunately, this stage of disease accounts for fewer than 20 percent of cases and results in approximately a 20 percent 5-year survival rate in patients with completely resected tumors. The 5-year survival rate for all patients with pancreatic cancer is only 4 percent. For patients with advanced cancers, the overall survival rate is less than 1 percent at 5 years with most patients dying within 1 year. Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery. However, palliation of symptoms may be achieved with conventional treatment.

7. How common is pancreatic cancer?

In 1999, it is estimated that 28,600 people will get pancreatic cancer, with the cases evenly divided between men and women. Because of the high mortality of the disease, 28,600 people are expected to die from the disease in 1999 (Note: Not all of the deaths are associated with cancers newly diagnosed in 1999).

For more information about cancer, visit NCI's Web site for patients, public, and the mass media at http://www.nci.nih.gov.

Date Created: December 1999

http://nccam.nih.gov/news/19972000/121599.htm