Other substances with lipoidic character but with a polar group different from the carboxyl were tested. Mercaptans, as lipoids with a thiolic negative polar group, were used. In 1942. we started to study the therapeutic effect of ethyl mercaptan injected intramuscularly, in a 10% solution in oil. (326)

Use of ethyl mercaptan had to be limited to subjects with an offbalance corresponding to a predominance of sterols. Although only a few patients were treated because of the offensive odor, the results were satisfactory as indicated by the following case histories.

F. C.—This patient, at the age of 66, had a small carcinoma of the tip of the tongue resected at Columbia Presbyterian Hospital on May 6, 1941. At the same time, a second carcinoma of the left lateral border of the tongue was found infiltrating into the deeper portions. This lesion was treated with radium needles with a total dose of 2500 mg. hours. In September 1941, a prophylactic left radical neck dissection was performed. The patient was well for 8 months thereafter, and then began to experience soreness in the region of the scar on the lateral side of the tongue.

In August 1942, 16 months after the tumor had been irradiated, the patient came under our care. At the juncture of the anterior and middle third of the left lateral border of the tongue, there was an induration of 2/1 cm. in dimension with an ulceration of 1/0.5 cm. covered by necrotic tissue. The indurated base was especially developed anteriorly to the ulcerated lesion. There was no evidence of recurrence at the scar of the tip of the tongue nor at the left side of the neck. The latter lesion was very tender. A Wassermann analysis was negative. Biopsy of the edge of the ulcerated tumor revealed squamous cell epithelioma.

The patient was treated with placental acid lipid fraction for the first week without any subjective or objective change. The treatment was changed and the patient received 1 cc. of a 10% solution of ethyl mer captan in oil intramuscularly, three times a day. The dose was increased after three days to 2 cc, three times a day. By the end of one week under this treatment, pain had disappeared, although there was still some burning sensation. The appearance of the lesion was unchanged. The treatment was continued. By the end of the second week, the edema was reduced, and after another week of the same treatment, the induration was gone. After one month of treatment with ethyl mercaptan, epithelization of the lesion was noted. The treatment was discontinued. The lesion appeared completely healed, without induration, burning sensation or pain, less than a week later. The patient has remained without treatment since, and there has been no recurrence in the last 18 years. Three years ago, the patient had a basal carcinoma of the skin of the nose, which responded well to local treatment with radium in Mexico.

Mrs. L. F.—In June 1942, the patient then 50 years old, observed an induration on the right border of her tongue. Biopsy revealed a squamous cell carcinoma. After the biopsy, the lesion progressed so rapidly that it was judged inoperable. Without having received any other treatment, the patient came under our care in August 1942. At that time, the tumor had involved the right half of the tongue and multiple submaxillary and neck nodes, the biggest being 2 cm. in diameter. The lesion was extremely painful. Urine analyses showed low specific gravity and high pH and the patient was treated with 10% ethyl mercaptan in vegetable oil. We started with three 1/2 cc. injections daily. The dose was progressively increased until it reached 6 cc. daily. The pain disappeared entirely in less than a week.

Treatment was continued for only 3 1/2 weeks at which time there was a marked improvement in the tongue lesion and lymph nodes. Except for an inflammatory reaction at the site of injection, no side effects were seen. A month after the start of treatment, the lesions had completely disappeared. No treatment has been given since. The patient is still well today, free of recurrence, 18 years after treatment with ethyl mercaptan.

H. A.—In May 1942, at the age of 52, the patient developed hematuria, pyuria and tenesmus. In June 1942 an infiltrating tumor of the right side of the trigone was revealed by cystoscopy and cystogram. The patient came under our care at the end of August 1942. Having high urinary specific gravity, he was treated first with insaponifiable fraction of placenta, receiving 1 cc. of a 5% preparation in oil three times a day. Hematuria and the other symptoms increased under the treatment which was then changed to ethyl mercaptan, 10% solution in oil, starting with Vi cc. three times a day. The dose was progressively increased to 3 cc., three times a day by the tenth day. Hematuria decreased in the first 48 hours and ceased completely on the fourth day. Other symptoms disappeared. The treatment was continued with this dose for another 2 1/2 weeks. Disappearance of the tumor was seen in follow up cystograms. Without further treatment, the patient remained well until the beginning of 1955, 12 1/2 years later, when a recurrence of the tumor of the bladder was noted. Being in Mexico, he did not receive treatment by this method and died from generalized carcinomatosis after 9 months. (Figs. 156 and 157)

Cystogram of patient H.A. before treatment

Fig. 156. Cystogram of patient H.A. before treatment.

Similar favorable results were obtained for other patients with patterns corresponding to sterol predominance. We treated only three patients with patterns indicating fatty acid predominance. The use of ethyl mercaptan in these cases caused an exacerbation of symptoms and rapid deterioration of the general condition.

The odor of ethyl mercaptan was so offensive that its use posed insurmountable problems. Patients were forced to be social recluses and it was practically impossible to get nurses to administer the injections because of persistence of the odor on skin and clothes. We had many complaints that the odor of the medication polluted the atmosphere of a large area for a long time. Obliged to discontinue its use, we sought other preparations containing thiol groups or bivalent sulfur that we hoped would have similar biological effects.

We investigated a large number of such substances in animals. Only a few were extensively studied in patients. Of the homologous series of aliphatic mercaptans, we utilized propyl, butyl and amyl mercaptans. These offered no advantage over ethyl mercaptan, being less active but hardly less offensive in odor.

Cystogram of patient H.A., after treatment with ethyl mercaptan

Fig. 157. Cystogram of patient H.A., after treatment with ethyl mercaptan.

Hexyl mercaptan was the first of the series that had a more bearable odor but it was definitely less active. Although objective changes in cancer were observed with its use, the tumors did not disappear as they did in some cases treated with ethyl mercaptan, and many favorable responses were only temporary.

Of the higher mercaptans, dodecyl and hexadecyl were most extensively studied. While their odor was far less objectionable, they produced less favorable results than the lower homologues. Much larger doses were required to influence pain, and even then the effects were reduced and temporary. The striking results obtained with ethyl mercaptan could not be duplicated with any of the higher homologues. For this reason, we reluctantly abandoned the use of mercaptans.