Parallel to these researches on fatty acids, the use of agents with positive polar groups also underwent changes. As previously mentioned, it appeared increasingly clear that no single agent could be effective in itself if an offbalance corresponding to predominance of fatty acids was present. Quite early in this research it could be observed that the simultaneous use of two agents from the same group appeared to be a better procedure than using either agent alone. In a limited number of patients treated with single agents, without impressive clinical changes, better effects were obtained when combinations were tried. Although it was difficult to ascertain in individual cases that favorable effects were due exclusively to change in medication, the following cases are interesting.

A. Ch., a 53-year old woman, had a radical mastectomy for an adenocarcinoma of the right breast with axillar and supra clavicular ganglionar involvement. Almost two years later—during the three months immediately prior to the time we first saw her—she showed rapidly developing multiple metastases for which only symptomatic treatment was applied. Along with multiple bone metastases, and a recent pathological fracture of the inferior third of the right femur, there were liver metastases and a right pleural effusion for which she had been tapped three times. When she came under our care, she complained especially of pain in the lower back caused by lumbar and sacrum metastases. Her condition was considered terminal so that the surgeon did not think it advisable even to apply traction for the fracture of the femur. It was under these conditions that we started to treat her with two injections a day of 1 cc. of a 5% solution in oil of the insaponifiable fraction of human placenta. Except for the unexpected survival of the patient, no apparent change was seen after two weeks of treatment. The pain, pleural effusion and general condition remained the same.

The treatment was changed to 5 drops of glycerol three times a day, and the dosage was progressively increased to 15 drops of glycerol t.i.d. After ten days without change, Coramine in doses of 15 drops was given when necessary to control the typical alkaline pain. After another week there was still no change. The pain remained almost the same, except for a decrease in intensity immediately following administration of Coramine. When all three substances were given concomitantly—the insaponifiable fraction by injection and glycerol and coramine orally—the situation changed impressively. Within a few hours, pain disappeared completely, and within one week other manifestations had totally changed. The pleural effusion, for which the patient had been tapped regularly each week or every 6 days, disappeared. The fracture which, until then, had appeared entirely inactive, showed a consolidation so rapid that in less than two weeks a solid callus was present. In three weeks the patient was out of bed on crutches. X ray pictures taken two months after the change in medication showed most of the osteolytic lesions replaced by new bone tissue and the fracture replaced by an abnormally solid callus. There was no fluid in the pleura. All treatment, except the glycerol, was discontinued after another three months when, at the start of the war, the patient left Paris. We heard that she continued in good health wihout further treatment for three more years, at the end of which time she developed a recurrence, with liver metastases, and died shortly thereafter.

M. R., a 58-year old woman, the wife of a professor of gynecology, had an ulceration of the cervix two years before coming under our care. Biopsy had revealed squamous carcinoma, Grade III. After local treatment with radium, she underwent total hysterectomy. Six months before we saw her, she developed multiple abdominal metastases for which only symptomatic treatment was prescribed. When she came under our care, she had a distended abdomen in which masses of various dimensions were easily palpable. Besides several large tumors, two of them about 15-20 cm. in diameter, there were many smaller ones which gave the distended abdomen a very irregular appearance. The abdominal pain, her generally poor condition, as well as severe edema of the legs, kept the patient bedridden. She showed a high urinary specific gravity and low pH, and treatment consisting of a daily injection of 2 cc. of a 2.5% solution of cholesterol in oil was prescribed. When no subjective or objective changes were seen in three weeks, the treatment was changed to 10 drops of glycerol orally, three times a day, for another three weeks. There was still no obvious change.

After another three week period, this time without treatment, during which her general condition deteriorated, mixed treatment with cholesterol and glycerol was started. The patient now made a sudden remarkable recovery. The edema of the legs disappeared rapidly and in less than a month the tumors were no longer palpable. The abdomen, however, continued to be distended, but instead of the previous irregularity with multiple well delineated tumors, a single huge mass was recognized. It filled practically the entire abdomen. We made the diagnosis of a large ovarian cyst which had probably been present before but had been obscured by the multiple tumors. The patient was operated on three months later and the cyst was removed. Not only were no tumors found in the abdomen, but there were no adhesions which the surgeon had feared. White patches were seen at the sites previously occupied by the tumors. There were no recurrences during several years of follow up, after which we lost track of the patient.

Similar results were obtained during the following years, indicating the value of mixed therapy. We made it our standard clinical treatment except when the pharmacodynamic effect of a specific agent was being investigated.

As an example of the objective changes obtained through mixed treatment for type D offbalance, we give an abbreviated form of the following observation.

Miss S., 39 years of age, came under our care with bone metastases from an adenocarcinoma of the breast, for which she had a radical mastectomy IVi years previously. At admission in very severe pain, besides other multiple bone metastases, she showed especially a marked destruction of the 6th and 9th left ribs. (Fig. 154) The analyses showed an offbalance type D and consequently she was treated with butanol and glycerol. The patient showed rapid changes not only in her subjective feeling, but also objectively. Fig. 155 shows the rib osteolytic lesions healed and the missing bone replaced by new bone.

Arterioposterior view of the chest of patient

Fig. 154. Arterioposterior view of the chest of patient S at time of admission showing an osteolytic process in the 6th and 9th left ribs.

Arterioposterior view of the chest of patient 5 months later

Fig. 155. Arterioposterior view of the chest of patient 5 months later, with the appearance of the new bones replacing the part of the ribs previously destroyed.

In general, however, in spite of some favorable cases, the results were not satisfactory. Even in patients in whom tumors regressed and disappeared, recurrences were seen anywhere from a few months to several years after discontinuation of treatment. By prolonging treatment over a period of years, the period of improvement was lengthened in some cases. Still, all too often the response to treatment was only temporary.