In 1947, we started therapeutic trials of conjugated fatty acids, first using eleostearic acid, the conjugated triene obtained from tung oil, administered orally or parenterally. The effects upon pain, systemic changes and particularly tumor evolution, were not up to expectation although subjective changes were immediately more manifest than for unconjugated fatty acids. In a short time, however, it was found necessary to continuously increase the dosage in order to maintain the effects. The intervention of a defense mechanism against these preparations often was evident. Cancer patients who had responded to administration of eleostearic acid with relief of pain and even with an arrest of tumor growth were found to require increasing amounts of this substance. After a while, they no longer responded. Even very large amounts of this conjugated fatty acid, well tolerated in these cases, no longer had an effect upon the tumor and its manifestations. This fading effect limited the clinical usefulness of eleostearic acid. In this respect, it appeared to resemble many other constituents or even heterogeneous agents which have therapeutic effects that fade rapidly.

We have noted previously that intervention of the adrenals is directed especially against the conjugated trienes, substances related to traumatic noxious influences. Therefore, we tried to utilize other conjugated members, some with a higher number of double bonds, in the hope that the body would not be able to efficiently fight their intervention. We obtained conjugated fatty acids with four double bonds by treating mixtures of fatty acids rich in arachidonic acid, such as salmon oil, then fractionating the mixtures through their solubility in solvents, especially acetone, at low temperatures. We also obtained the same type of compound directly from parinarum laurinum nuces as parinaric acid, a tetraconjugated acid. Conjugated pentaenic and hexaenic acids were isolated from the mixture of conjugated fatty acids obtained from salmon, sardine and cod liver oils. When these preparations were tried in patients with cancer, no apparent improvement over the results obtained with mixtures of non conjugated fatty acid was seen.

Having in mind the plurality of levels at which they would act, and especially considering the influence exerted by methylcholanthrene upon carcinogenic activity, mixtures of fatty acids from cod liver oil, sardine oils and from normal organs and tissues were conjugated and used. While the effects on pain and systemic changes were more intense and longer lasting, the effects upon tumors were not strikingly different from those obtained with the non conjugated isomers. Of approximately 140 cases in which these conjugated fatty acid preparations were used, 45% showed subjective changes. In 25%, objective changes occurred, including clinical disappearance of malignant tumors in a few cases. Most of these results, however, were temporary. The tumors later grew again and no longer could be controlled by administration of these lipids. In some cases, the good results persisted and the following illustrates three of these cases.

B. T., 46 years old, had a left mastectomy in 1948, for an adenocarcinoma. 1 1/2 years after the operation, progressively increasing generalized pain appeared, with the general condition going rapidly downhill. Pain, more than the general condition, obliged her to become totally bedridden. Successive X ray examinations showed rapidly progressing osteolytic lesions. X ray treatment for three regions was started with the intention to control the pain which was most severe in skull, ribs, spine, pelvis and femurs. Because of the general condition, this was discontinued after a few treatments. When the patient came under our care, she was entirely immobilized and in severe pain. X rays revealed (Figs. 178, 179) multiple osteolytic metastases in skull, femur, pelvic bones, spine. In view of the analysis as a typical A offbalance, treatment with hydropersulfide and conjugated fatty acids was instituted.

Lateral view of the skull of patient (B.T.) at the time of admission

Fig. 178. Lateral view of the skull of patient (B.T.) at the time of admission, showing multiple osteolytic metastases.

In her case we saw a peculiar form of response encountered also in several other subjects, and which we considered in general as corresponding to as a favorable response. During the treatment, while pain in general was relieved, one lesion was seen to become progressively more painful. It remained severely painful for 2-3 days after which the pain disappeared. The same change was seen to occur successively in one lesion after another with the same temporary increase of pain until it became very severe, followed by disappearance after 2-3 days. Not only did the pain fail to return in the same lesion, but usually the lesion was seen to involute after such a change.

With this kind of treatment the patient made a very rapid recovery and was out of bed in less than two months. The radiological changes, although showing progressive repair of the osteolytic lesions, took more time to be completed Fig. 181 shows the healing of the bone metastases in progress, while Figs. 180 and 182 the results after almost 2 years. The patient resumed normal life for 3 years after which recurrences appeared on skin, lung and liver. These responded less favorably to the same treatment. The patient left our care and died a few months later.

Anteroposterior view of the pelvis and upper parts of the femurs of the patient

Fig. 179. Anteroposterior view of the pelvis and upper parts of the femurs of the patient (B.T.) showing multiple osteolytic metastases.

Mrs. S. T., 47 years old, came under our care in a subcomatous state, 2 1/2 years after a left breast mastectomy for an adenocarcinoma. For three months before, the patient complained of generalized pains and especially of severe headaches, and for a month had symptoms of diabetes insipidus.

Lateral view of the skull of patient (B.T.)

Fig. 180. Lateral view of the skull of patient (B.T.) after 22 months of treatment. Most of the lesions have disappeared.

An X ray examination of the skull, made prior to her admission (Fig. 183) showed extensive skull metastases with an advanced destruction of the clinoid bones.

Because of the diabetes insipidus, the urine analyses could not furnish the needed indication for the treatment and we recurred, therefore, to the number of blood leucocytes and to the body temperature, as tests able to indicate the existing offbalance. With 14,500 leucocytes and a constant temperature of above 98.6 F, we considered the offbalance to be of the type A and administered conjugated fatty acids obtained from cod liver oil, and sodium thiosulfate together with posterior pituitary hormone for her diabetes insipidus. Probably due largely also to her electrolytic balance the patient regained consciousness and made a rapid recovery. In less than two weeks she was out of bed and resumed a normal life. She continued with the same treatment on an ambulatory basis. An X ray examination four months later showed a manifest healing of the previous lesions. (Fig. 184)

Anteroposterior view of the pelvis and femurs of patient

Fig. 181. Anteroposterior view of the pelvis and femurs of patient (B.T.) after four months of treatment, showing the lesions decreasing.

Anteroposterior view of the pelvis and femurs of patient (B.T.) 2 years later

Fig. 182. Anteroposterior view of the pelvis and femurs of patient (B.T.) 2 years later, showing most of the lesions disappeared.

After another four months however, without any recurrence of her malignancy the diabetes insipidus could not be adequately controlled. She refused hospitalization and left our care. She died a short time later with symptoms of electrolytic offbalance.

Mr. L. N.. 64 years old, had a long history of vesical troubles, with biopsies showing cancerous lesions. In spite of repeated figurations, the vesical tumors grew rapidly with constant hematuria and tenesmus. Three months before coming under our care, the patient suffered severe pains in the left groin which X ray examination showed to be due to a bone metastatic lesion. Fig. 185 depicts the lesions upon admission. The analyses showed an offbalance type A, and a treatment with conjugated fatty acid obtained from cod liver oil and sodium thiosulfate was instituted. The pain disappeared in a few days, as did the hematuria and dysuria. The patient continued to improve. An X ray examination, four months after treatment was started, showed the appearance of a callus at the place of the bone metastases. (Fig. 168) The patient continued the treatment for a few more months after which time we lost track of him.