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July 8, 2002

Nutritional Therapy for Primary Peritoneal Cancer: A Case Study - Alternative Therapy
Guisseppi A. Forgionne, PhD

Primary Peritoneal Cancer

Alternative and Complementary Therapies
Scientific Theories and Suggested Pathologies

Case and Empirical Studies
Suggested Therapies
Figure 1- Cancer Progression Free Rates
Figure 2 - Cancer Pathology

Table 1- Nutritional Therapy Studies Nutritional Therapy for Primary Peritoneal Cancer: The Case Study

Nutritional Therapy for Primary Peritoneal Cancer: A Case Study - References

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There are a variety of treatments available for ovarian and primary peritoneal cancer. Surgical debulking is the primary initial treatment. Depending on the stage and grade of the disease, surgery may be followed with chemotherapy, radiation, or other experimental interventions.

The conventional or standard treatment for higher stage and grade disease is chemotherapy. The goal of this therapy is to retard the progression of the cancer. In the short-run, the success of the chemotherapy is measured in terms of CA-125 test levels, CT scan results, and second-look surgeries. Long-term success is measured in terms of 5 year survival rates.

Standard chemotherapy has not produced a cure for ovarian and primary peritoneal cancer. The treatment also has rather severe adverse effects, including nausea, hair loss, vomiting, and increased susceptibility to other diseases. Consequently, researchers have been seeking alternative treatments for the disease.

Gene and hormonal therapy, immuniology, radiology, and nonconventional chemotherapy are among the alternative medical treatments being explored. To date, these treatments have been unsuccessful or unproven when compared to conventional chemotherapy in reducing ovarian and primary peritoneal cancer morbidity and mortality. In addition, the experimental approaches generate significant side effects.

Nutritional therapies have been suggested as complementary or alternative treatments for ovarian and primary peritoneal cancer. There have been some scientific investigations of these alternative or complementary treatments. In some alternative investigations, the study design has been criticized, while in others, the scope and tracking have been very limited. For these reasons, the alternative investigations have yielded inconclusive results.

This paper reports the results of a case that utilized combination nutritional therapy as a first line therapy following surgery for Stage IIIA, Grade 3 primary peritoneal cancer expressed in the left ovary and omentum. First, there is a presentation of the general physiology for the disease, traditional first line, post surgical therapies, and the empirical morbidity and mortality statistics associated with these traditional treatments. Next, the paper examines the scientific theories involved in the traditional therapies, contrasts the theories with the science behind nutritional therapies, discusses case and empirical studies of these alternative scientific theories, discusses the theorized pathologies, and presents the suggested alternative therapies. This discussion is followed with the particulars of the reported case, including the patient's medical history, post surgical pathology report, and nontreatment prognosis. Then, there is a presentation of the alternative treatment, including the nutritional regime, the patient's general health progression, and the clinical test results. The paper concludes with an examination of potential moderating factors, alternative clinical explanations, medical implications, and future research suggestions.

Primary Peritoneal Cancer
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Primary peritoneal cancer is a malignancy originating in the tubular or ephitelial tissue in the peritoneal cavity. Since the disease yields nonspecific symptoms, it frequently is not diagnosed until it has metastasized.

General Physiology
The disease spreads through uncontrolled and signaled cell growth that eventually damages and destroys organs vital for life. Depending on the grade or maturity of the cancer, spreading can be slow or rapid. Affected organs can include the ovaries, uterus, omentum, abdomen, liver, and brain, among others .[29]

The metastatic process is achieved by the cancer cell signaling adajacent healthy cells. Signals are sent through chemicals found in the cancer cell. [30] In healthy humans, such spreading is avoided by DNA programming that encourages out of control cells to essentially destroy themselves through a chemically induced process and/or by the immune systems's attack on the cancer cells. [2, 31]

A number of theories have been advanced to explain why the cell death process breaks down in cancer patients. Some believe that a cancer cell lacks essential enzymes that trigger self-destruction.[28, 42] Others proffer that the cancer cell disguishes itself from the body's immune system, either through an encapsulation process or by disguishing itself as a nonforeign body. Left uncontrolled, the cancer cell continues to multiply into masses that eventually engulf essential human organ tissue.

The metastatic process is both painful and debilitating. Uncontrolled growth creates pressures against organs and nerves. Simultaneously, cancer cell growth drains essential nutrients needed by organs for human maintenance [28, 29].

First Line Therapies
Cancer research has provided several therapies to treat primary peritoneal and ovarian cancer. Foremost is debulking surgery, where cancerous tissue is identified and removed by resection. Depending on the result of a pathological investigation of the resected tissue, this initial treatment may be followed by chemotherapy, radiation, or other experimental interventions. [28, 54]

In some cases, the cancer is at Stage I, where the carcinoma is confined to the ovary (or ovaries), and resection eliminates all diseased tissue. For such cases, further treatment may be unnecessary. Other instances involve metastastis to other pelvic tissue (Stage II), to admominal tissue (Stage III), or beyond (Stage IV). Such metastastis usually suggests a round of chemotherapy and/or directed radiation (if the cancerous expansion can be isolated and is relatively small). These postoperative treatments are still considered first line therapies. [54 ,67]

Empirical Morbidity and Mortality Statistics
Surgery is usually a significant event that involves a large incision to open the abdominal cavity. The uterus, both ovaries, and the Fallopian tubes are usually removed, as well as the omentum and possibly suspicious lymph nodes. Such surgery is traumatic, and afterwards the patient usually requires a significant hospital stay and home recovery period. Except in Stage I cases, surgery is only the first step in the treatment of the disease. Even in Stage 1 cases, surgery may be a first step treatment. [54]

Chemotherapy involves the use of a variety of chemical agents that attack and destroy fast-growing cells throughout the body. These fast growing cells include blood, hair, and others, as well as cancer cells. Consequently, the side effcts of this treatment are rather substantial, and include hair loss, nausea, vomiting, heart disorders, infections, and immune system disorders. [67] Typically, additional agents are administered to counteract or minimize the side effects.

In cases where the cancer is confined to a relatively small area, the chemotherapy may be administered directly to the diseased site and/or radiation may be targeted to the location. Since these targeted therapies are not systematic treatments, the side effects are less severe than with general chemotherapy. Still, the side effects are substantial and include nausea, vomiting, and others. [28,54]

The goal of standard postsurgical first line therapies is to eradicate as many cancer cells as possible. Success is usually measured by CA-125 test results and five-year survival rates. Since it may be impossible to eradicate every single cancer cell and because cancer cells become resistant to the chemical agents, chemotherapy and radiation cannot be thought of as cures for the disease. [28, 54, 67] Instead, they are usually viewed as vehicles to manage the disease.

graphic showing fewer and fewer surviving each year from 84% first year to 26% fifth year The empirical statistics suggest that the conventional viewpoint is correct. Five-year survival rates (upwards of 95%) are encouraging for Stage 1 cases and become increasingly grim as the stage and grade of the disease increase. According to the public literature, five-year survival rates are for 65% Stage II, 20% for Stage IIII, and 5% for Stage IV patients. [54] It is also significant to note that a substantial portion (5%) of even Stage I patients eventually die after only 5 years.

Even with successful conventional first line therapies, the empirical findings are not particularly encouraging. Figure1 - Cancer Progression Free Rates   which shows progression-free, rather than survival, rates from a recent chemotherapy study on mainly Stage III patients, illustrates the point. As this figure indicates, 84% of the treated patients exhibited progression-free conditions after one year. By the fifth year, only 26% of the treated patients remained progression-free. [43]

Alternative and Complementary Therapies
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Because of the significant side effects of traditional first line therapies and the grim eventual outcomes for most patients from these therapies, researchers have sought alternative and complementary forms of treatment. [12] These alternative and complementary approaches include gene therapy, hormonal therapy, immunology, and nutritional regimes. [28 ,30, ,31] In gene therapy, there is an attempt to correct, through chemical agents, the breakdown in the DNA process that leads to cancer. [9] Hormonal therapy seeks to replace essential chemicals lost during the cancer's progression and thereby control cancer growth through this replacement. Immunology seeks to induce the human immune system to identify, locate, and attack the cancer. Stimulation may be provided through chemicals, cancer cells, and other agents. Nutritional regimes utilize readily available foods and supplements, rather than synthetic chemicals and agents, to achieve physiological effects similar to gene, hormonal, and immunological therapies. [45,49, 65]

Scientific Theories and Suggested Pathologies
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There are four scientific theories that are the basis for the alternative and complementary therapies. These theories can be illustrated with the aid of Figure 2 - Cancer Pathology cartoon showing the process of cancer cell

- One theory is based on the formation of blood vessels by the cancer cell. In this theory, cancer cells form blood vessels to obtain nutrients from the body that serve to promote growth and development. [25, 37] According to the theory, cancer growth and development can be reduced, or potentially eliminated, by retarding the blood vessel production process. In Figure 2 - Cancer Pathology , this process would remove the blood vessels emanating from the cancer cell.

- A second theory is based on an encapsulation process. In this theory, the cancer cell encapsulates itself in a protein that disguishes the cancer cell from the immune system. This theory suggests that the cancer cell can be unmasked by breaking down the protein cover and then destroyed by the human immune system. [28] Since the human immune system's normal production of killer cells may be insufficient in quantity and potency to destroy rapidly growing cancer cells, the immune system's defense also requires a boost to complete the destructive process. [1] In Figure 2 - Cancer Pathology , this process would remove the protein capsule and radiate the cancer cell with immune system killer cells.

- A third theory revolves around a signaling process. In this theory, the cancer cell sends a chemical signal to adjacent cells that trigger the uncontrolled growth and development process. Put another way, the signal transforms the healthy adjacent cell into a cancer cell. [4, 23, 53] According to the theory, the process can be retarded, or arrested, by blocking the chemical signal. [15, 25] This action would remove the chemical signal arrows emanating from the cancer cell in Figure 2 - Cancer Pathology

- A fourth theory focuses on deficiencies observed in cancer patients. In this theory, such patients are missing either essential genes, chemicals, or nutrients found in healthy people. [13, 52] This theory suggests that cancer can be retarded, or potentially eliminated, by resupplying the missing genes, chemicals, or nutrients. [18] In Figure 2 - Cancer Pathology, the resupply would transform the cancer cell into a healthy adajcent cell.

Case and Empirical Studies
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A number of empirical and case studies have been conducted to evaluate the various scientific theories. Some of the studies have involved experimental gene and hormonal therapy, while others have involved nutritional regimes. [17, 44, 46, 58, 59,68, 69] There have been laboratory studies involving chemical processes, in vitro cells, and animals [13, 19, 22, 33, 47,51, 71]. A few clinical trials have been performed with humans, and there have been case studies involving humans. Table 1- Nutritional Therapy Studies summarizes the major human studies.

Table 1 - Nutritional Therapy Studies
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Nutrient Reference Findings
Bovine cartilage Prudden [56]

Case series of 31 patients reported that 19 patients had a complete response, 10 patients had a partial response, and one patient had stable disease following Catrix® treatment. The remaining patient did not respond to cartilage therapy. Eight of the patients with a complete response received no prior or concurrent conventional therapy. Approximately half of the patients with a complete response eventually experienced recurrent cancer.

Bovine cartilage

Romano, et al. [60]

A Phase II clinical trial of 9 patients reported that one patient (with metastatic renal cell carcinoma) had a complete response that lasted more than 39 weeks. The remaining eight patients did not respond to Catrix® treatment.

Bovine cartilage

Pucio, et al. [57]

35 patients with metastatic renal cell carcinoma were divided into four groups, and the individuals in each group were treated with identical doses of subcutaneously injected and/or oral Catrix®. Three partial responses and no complete responses were observed among 22 evaluable patients who were treated with Catrix® for more than 3 months. Two of the 22 evaluable patients were reported to have stable disease and 17 were reported to have progressive disease following Catrix® therapy.

Coenzyme Q-10

Lockwood, et al [39]

Thirty-two patients received antioxidant supplementation, other vitamins and trace minerals, essential fatty acids, and coenzyme Q10, in addition to standard therapy. The 18-month survival rate was one hundred percent (four deaths were expected), and 6 patients were reported to show some evidence of remission. None of the six patients had evidence of further metastases. For all 32 patients, decreased use of painkillers, improved quality of life, and an absence of weight loss were reported.

Coenzyme Q-10

Lockwood, et al [40]

In a followup study report, the researchers noted that all 32 patients from the original study remained alive at 24 months of observation, whereas six deaths had been expected.

Coenzyme Q-10

Lockwood, et al [41]

In another report by the same investigators, three breast cancer patients were followed for a total of 3 to 5 years on high-dose coenzyme Q10 (390 milligrams per day). One patient had complete remission of liver metastases (determined by clinical examination and ultrasonography ), another had remission of a tumor that had spread to the chest wall (determined by clinical examination and chest X-ray), and the third patient had no microscopic evidence of remaining tumor after a mastectomy (determined by biopsy of the tumor bed).

Coenzyme Q-10

Folkers [20]

Anecdotal reports of coenzyme Q10 lengthening the survival of patients with pancreatic, lung, rectal, laryngeal, colon, and prostate cancers. The patients described in these reports also received therapies other than coenzyme Q10, including chemotherapy, radiation therapy, and surgery.

As Table 1 - Nutritional Therapy Studies indicates, most of the results have been inconclusive. The few conclusive studies have been challenged on design, testing, and evaluation grounds. Hence, it is safe to say that none of the theories have yielded conclusive results.

There has been sufficient favorable evidence, however, to encourage further research. Some of the additional research has involved funded clinical trials. Other research is privately funded and subject to limits on disclosure. The research suggests a number of therapies for the treatment of cancer utilizing nutritional ingedients.

Suggested Therapies
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Coenzyme Q-10 is a chemical naturally occuring in human cells. This enzyme is essential to the health of cells. Research has shown that coenzyme Q-10 is greatly depleted in the cells of cancer patients. [21, 33, 48, 55] Additional research has shown that the enzyme may act as an antioxidant and as a stimulant to the human immune system. [7, 18, 35, 50] A third stream of research indicates that coenzyme Q10 may disrupt normal biochemical reactions that are required for cell growth and/or survival and thereby serve as chemotherapeutic agents. [5, 19, 27, 50]

This research suggests that the enzyme can be used to treat cancer by:
- (a) retarding the growth of cancer cells,
- (b) replenishing depleted enzyme and thereby promoting the transformation of the cancer cell to a healthy cell, and
- (c) boosting the production of immune system killer cells for an attack on the cancer cell.

Studies indicate that the relevant dosage is from 90-300 mg of coenzyme Q-10 per day [12

According to some research, bovine cartilage has chemical ingredients that may retard the growth of blood vessels to cancer cells. [6, 9, 62, 63] Other research indicates that the cartilage may generate a chemical reaction that is toxic to, and inhibits the growth of, cancer cells. [11, 16, 26, 38, 61, 64] A third stream of research indicates that bovine cartilage stimulates the human immune system. [3, 9 This research suggests that bovine cartilage can be used to treat cancer by:
- (a) retarding the growth of nutrient-supplying blood vessels to the cancer cell,
- (b) poisoning cancer cells, and
- (c) stimulating the human immune system to attack the cancer cell. Studies indicate that the relevant dosage is 9 grams per day. [69]

Wheat grass is a nutrient that has a similar chemical composition to hemoglobin. Consequently, it has a high oxygen content. It also provides a wide range of minerals and vitamins at substantial levels. Purportedly, these contents significantly boost the production of killer cells by the human immune system. [32] Others have proposed that the grass induces gene changes that retard chemical signals sent from the cancer cell to adajcent healthy cells. In the process, the cancer growth and development process is severely compromised, or potentially eliminated. Another proposition is that the wheat grass contains enzymes that will break down the protein that protects cancer cells, thereby exposing the diseased cell to attacks by the enhanced immune system. [32, 36] The indicated dosage is 2-6 grams of wheat grass per day. [32] Little formal research has been reported on these propositions.

Taken together, a daily nutritional regime of wheat grass, bovine cartilage, and coenyzme Q-10, then, implements the four main scientific theories for alternative cancer treatment. Wheat grass breaks down the cancer's protective protein capsule, retards the cancer cell's chemical signal to adjacent cells, and boost the immune system's production of killer cells. Bovine cartilage also stimulates the immune system, poisons cancer cells, and retards the expansion of the cancer's nutrient supplying blood cells. Coenzyme Q-10 also retards the growth of cancer cells, replenishes an ingredient essential to healthy cell maintenance, and also boosts the immune system.
Guisseppi A. Forgionne, PhD
Information Systems Department
University Of Maryland Baltimore County
Catonsville, MD 21250

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