In recent years, the course of our research has been directed parallel toward the precise application of available agents as well as finding new substances. For it has become increasingly evident to us that it is the basic independence of the different levels of organization in the body which represents the critical factor in the pathogenesis of cancer and its manifestations and which is also critical to the most effective use of therapeutic agents. This concept has led us to focus our research efforts in certain areas. Attempts are made to find criteria capable of indicating changes at specific levels of organization. Similarly, a growing awareness that each element belongs to a specific level of biological organization and exerts its biological activity primarily at this level has led us to try to use specific elements in correcting dysfunctions at various levels. Because of the independence of the levels, we have attempted to trigger the defense mechanism at appropriate individual levels rather than indiscriminately. This is especially important when the failure of the defense to operate at some one level represents a major factor in allowing pathological states to advance.

While each of these developments has been important, it has been the use of all three which has brought marked progress in the clinical application of the method in the last years.

With the concept of independence of levels, the use of more than one agent is not simply a matter of synergistic activity, but rather of employing several agents, each capable of acting at its proper level in complex conditions where more than one level is involved. To make this possible, it has been necessary to relate analytical data to changes occurring at specific levels. For example, changes in potassium in serum and red cells have been related to cellular level abnormalities; urinary surface tension changes, to metazoic; specific gravity to systemic; urinary pH and blood eosinophiles, to tissular. This has guided the choice of agents: selenium preparations, epichlorohydrin and heptanol for the cellular level; sulfurized hydronaph thalenes, lipoacids, unsaponifiable fractions and glycerol for the tissue level; magnesium and sodium thiosulfates, propionic aldehyde and butanol for the organ and organism levels. Through this approach, therapy has evolved toward what we can now consider to be biologically guided level chemotherapy.

The following observations show the role of these level indications in the conduct of the treatment.

F. R., in March of 1957, had a left mastectomy for an adenocarcinoma of a mammary gland. In July of 1958, she began to experience pain in the lower back and legs. In the three months prior to coming under our care, several skin nodules and some progressive difficulty in breathing was evident and there was a loss of 25 lbs. in weight. On admission, multiple skin and subcutaneous lesions, some of them measuring 3-4 cm in diameter were found, as well as 3 or 4 nodules in the right breast. The ambulant patient started treatment with selenium and epichlorohydrin. Although treatment was followed with irregularity, improvement was seen in the local lesions. In December, 1959, however, the difficulty in breathing had markedly increased and oxygen administration was needed. In less than a week her condition worsened. The treatment with more selenium and epichlorohydrin appeared unable to control the situation. She was admitted to the hospital in extreme dyspnea. The suppression of oxygen for even a few minutes was followed by convulsions. Radiological examination showed a very limited exudate especially in the right hemithorax, but multiple matastases in both lungs. All the analyses showed an offbalance of type A. Considering the condition as manifested also at the organic and systemic level, to the treatment with epichlorohydrin, acting at the cellular level, we added bixine and propionic aldehyde. The first agent was considered to act at the tissular level and the latter at the systemic level. With this treatment the patient made a very good and constant recovery. In less than two weeks it became unnecessary to use oxygen and her general improvement progressed so that 3 months after treatment was started, the patient was able to resume part of her housework. With mixed treatment—epichlorohydrin acting at the cellular level, and bixine and propionic aldehyde at the organic and systemic level—the condition seems controlled. The pulmonary metastases seen in previous X rays have also disappeared and all the skin nodules decreased rapidly, most of them having completely disappeared. She is at present in good state of health, doing all her own housework.

Mrs. C. H., 60 years old, came under our care two years ago with a history of lymphosarcoma with two positive biopsies of the inguinal glands, complaining especially of pain in the abdomen. On examination, inguinal, axillar and cervical glands were present, some of them 4 cm in diameter. With treatment of sodium thiosulfate and fatty acid hydropersulfides in relatively small doses, the pain was sufficiently controlled. After two months of treatment, the patient experienced extreme pain and a tumor of the head of the right humerus. In view of the local lesions with analyses which all showed an intensive offbalance of type A, the treatment was changed to epichlorohydrin and heptyldiselenide. Administering these agents in relatively high doses, it was possible to not only control the pain in a few hours, but to have the lesion disappear in less than two weeks, as did also all the abnormal glands. However, in spite of these objective very good results, the general condition became unsatisfactory, especially with marked weakness. Changes in the doses of medication or the temporary discontinuation of the medication, failed to correct it. It was only when propionic aldehyde considered to act upon the organism level was administered, that a rapid change toward a feeling of general well being was obtained. At present, with small doses of propionic aldehyde the patient is entirely free from any subjective or objective abnormal manifestations and has been so for almost a year.

Mrs. E. R., 42 years old, had a radical mastectomy for an adenocarcinoma of the breast. After 1 1/2 years, she experienced persistent back pain which was first diagnosed as arthritis. X ray studies and a myelogram made at Montefiore Hospital showed two metastatic lesions at the 1st and 2nd lumbar. Surgical intervention was thought to be not indicated. X ray therapy neither relieved the pain nor made it possible for her to leave her bed. At admission under our care, the patient was in severe pain and unable to even turn in bed, although she was still able to move her legs and their sensitivity was conserved. A treatment with heptyldiselenide, propionic aldehyde and bixine made the pain disappear and up to date the patient is leading a normal life, after having been bedridden for 8 months.

Mrs. M. McB., 62 years old, came under our care for a basocellular carcinoma of the left side of the face, near the inferior eyelid. Advised to undergo surgery, which would enucleate the left eye, she refused the operation. A biopsy was performed (Fig. 192) showing the presence of a basocellular carcinoma. She was treated with hexyldiselenide and with sodium thiosulfate, and the lesion disappeared within a few weeks. No recurrence was observed during the past 6 years.

Photomicrograph of the biopsy made on patient M.McB. showing a basocellular carcinoma

Fig. 192. Photomicrograph of the biopsy made on patient M.McB. showing a basocellular carcinoma.

Mr. G. Z., 56 years old came under our care for a lesion of the upper lip. Biopsy proved it to be a squamous cell carcinoma. (Fig. 193) The patient refused surgery or radiation which we advised. Following the biopsy the tumor started to grow rapidly, as seen in Fig. 194. According to the analyses, the patient was treated with fatty acid hydropersulfide. The lesion disappeared in less than 2 weeks. (Fig. 195) No recurrence was observed although the patient was no longer under treatment. The patient died 8 months later from a coronary occlusion.

The ability to induce changes at single specific levels has altered completely what was once a gross dualistic approach. Until recently, we had considered it inadvisable to induce therapeutic changes at a single level if offbalances were present at more than one level. With the concept of level independence, it has become part of the method to attempt to influence the level in which the predominant abnormality is present rather than to induce gross changes at all levels. In cases with general offbalance A but predominant at the cellular level, therapy to induce offbalance D limited to the cellular level alone, with the metazoic remaining at offbalance A, has produced interesting objective clinical results. Similarly, good results have been obtained in cases with predominant offbalance D at the cellular level and in the metazoic compartment, with treatment directed at changing the systemic and tissular offbalance D into type A without influencing the offbalance D at the cellular level. It is interesting to note that in both types of cases the changes lead ultimately to the same overall pattern of offbalance—D for the cellular level and A for the metazoic compartment.

Patient G.Z. before treatment

Fig. 193. Patient G.Z. before treatment.

The tumor grew rapidly following biopsy

Fig. 194. The tumor grew rapidly following biopsy.

Patient G.Z. after treatment

Fig. 195. Patient G.Z. after treatment.

Level chemotherapy with selenium, heptanol, propionic adlehyde and other agents, has given highly gratifying results. It led us to the present form of treatment, with particularly good results. In a variety of tumors, some impressive because of their huge dimensions or because of their high degree of malignancy, the immediate objective response has been striking. Massive lung metastases from breast cancer, generalized abdominal metastases from colon carcinoma, bone metastases from breast or prostate, and metastatic melanoma are among the cases which have responded and we are now waiting for time to indicate whether the results have lasting value.

While we were convinced in the past of the inherent potentiality of the method in general, because of results with many different agents and criteria, we have been greatly encouraged by the most recent applications. We believe the method now provides a means of controlling a significant proportion even of preterminal and terminal cases of malignancy considered otherwise entirely beyond any hope. The particularly favorable results obtained in the cases which came under our care before the disease had progressed to advanced stages indicate that we are fully entitled to prefer this therapeutic method even for those cases where the presently used procedures might still have a chance to help.