Clinical studies on patients with cancer

Patients with the following tumours have been tested using fatty acids:

1. Gliomas and astrocytoma:

Local delivery of GLA (intra-cerebral) in 15 patients with malignant gliomas resulted in regression when evaluated by computerised tomography and increased survival of the patients by 1.5-2 years (119). Patients with cerebral astrocytoma showed improvement in general condition as well as tumour (120).

2. Breast cancer:

As already discussed, there have been significant interests and controversies in the effects of PUFAs on breast cancer. A recent clinical study has tested 32 patients with breast cancer with tumour spread to the lymph nodes in the axilla, by giving patients a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q(10) (90 mg per day). It is very interesting to note that none of the patients died during the study period (18 mths) (the expected number was four). None of the patients showed signs of further distant metastases and quality of life was improved (no weight loss, reduced use of pain killers). Further to this, six patients also showed apparent partial remission (121).

3. Pancreatic cancer:

A recent multicenter study of 48 patients with advanced pancreatic cancer showed (127) that Infusion of GLA increased survival. Eighteen patients with unresectable pancreatic cancer receiving dietary supplementation orally with fish oil capsules containing eicosapentaenoic acid 18% and docosahexaenoic acid 12% also had an improvement in weight loss and cachexia (122). It has been suggested that this anti-cachectic effect of EPA was due to its regulation of acute phase proteins and inflammatory cytokines such as IL-6 and TNF.

4. Colorectal cancer.

60 patients with sporadic adenomas receiving fish oil which was high in EPA showed a decrease in the proliferative indices and mucosal arachidonic acid levels (123). However, the beneficial effects seen in these studies have not been repeated in a controlled trial with late stage colorectal cancer, in which patients with Dukes's C colorectal cancer receiving GLA did not have benefit in terms of survival (124).

5. Liver cancer:

Van der Merwe (120,125,126), in a double blinded trial in patients with liver cancer, indicated an improvement in survival (42 days in control group and 90 days in GLA treated group) and retardation of tumour growth in these patients. In these studies, GLA was delivered in the form of evening primrose oil (120). This may reflect the observations made in in vitro studies that liver cancer cells are amongst the most sensitive cells to GLA.

6. Other tumour types.

Fatty acid (GLA) has also been given to patients with malignant mesothelioma, renal cell carcinoma, lung and gastric carcinomas (120). Although clinical improvement and weight gain were observed in these patients, the sample number was too small to make a fair assessment and more extensive studies are required.

Polyunsaturated fatty acids have been demonstrated to play a role in the regulation of the invasive and metastastic behaviours. So far, most evidence has come from in vitro studies. However, animal studies and certain epidemiological studies have revealed a possible link between the amount, and the type, the purity of these lipids with cancer metastasis. Early clinical studies have shown signs of promises in using PUFAs as a possible means of treatment of cancer and cancer metastasis. However, there remains a large number of un-answered questions and controversies, as already discussed in the previous sections. Some of the key issues are high lighted in the following. 1 .The key mechanism, by which PUFAs regulate invasive/metastatic

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process. We yet have to develop a core explanation to the diverse effects exerted by PUFAs in the metastatic process. 2. The potential mechanisms by which PUFAs govern gene transcription. It is unlikely that any one mechanism can fully elucidate the nuclear actions of PUFA. As regulators of gene expression, PUFAs (or metabolites) are thought to affect the activity of transcription factors, which in turn target key cis-linked elements associated with specific genes. This will be a potential interesting area to explore. 3. Narrowing the gap between in vitro and animal studies, between animal study and human studies. 4. Improve formulae that may allow more effecient delivery to patients. 5. Development of effective combination between other forms of therapy, such as chemotherapy, radiotherapy and hormone therapy.

Acknowledgement

The authors would like to thank the World Cancer Research Fund (WCRF) for supporting this work.

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