Cancer Treatment Using Anticancer Preparation Alkaloid Derivative Ukrain

J. W. NOWICKY

Ukrain is a semisynthetic, self-fluorescent alkaloid derivative of the plant Chelidonium majus L., or greater celandine, and thiophosphoric acid triaziridide (Thio-TEPA). Thio-TEPA was chosen on the basis of its alkylating property as a connecting link between the alkaloids. The preparation contains no unbound Thio-TEPA, The toxic dose in test animals is 10,000 times higher than the therapeutic dose1. Although «ukrain» exhibits no significant effect in experimental animal models and in tissue cultures, a definite positive effect was demonstrated in spontaneously-grown tumors in dogs. The essential part of ukrain's effectiveness lies in its ability to stimulate the immunological system. This was demonstrated in the lymphocyte-transformation test. Ukrain is a stronger stimulator than the control substance phytohemagglutinin (PHA) and seems to have a more specific action. In some cases, unlike PHA, ukrain leads to no stimulation. This correlates with clinical observations that a small number of patients, independent of tumor type, showed no response to treatment with ukrain. In the «oxygen» experiment preparation ukrain demonstrates a novel property. It causes an increase in the oxygen consumption of both normal and malignant cells. This normalises after approximately 15 min in the case of normal cells, whereas with malignant cells it drops towards zero. The cells stop breathing. This specific pharmacological effect on malignant cells has never been described in any literature for any substance 1, 2. Yet another interesting properly of ukrain is the clearly visible yellow-green fluorescence under ultra-violet light. This fluorescence phenomenon has been demonstrated both in animal tests and in the clinic. Only a few minutes after ukrain has been administered intravenously it accumulates around the tumor. The tumor thus becomes visible and metastases can also be detected1. The following are 3 case reports.

Case No. 1

In February 1983, a 45-year-old female patient was examined for a hard, indolent node in the lower outer quadrant of the left breast. Results of a mammography show the tumor. Beside it there were mastopathic changes and absent involution of the grandular tissue. There were suspect lymph nodes in the left armpit which were detectable palpably as well as on X-ray.

Since the patient rejected the idea of an operation, monotherapy with ukrain was carried out. The therapy consisted of 5 injection series until March 1984. At the beginning of therapy a feeling of warmth appeared throughout the body, accompanied by tiredness and slight nausea. In particular, there were stabbing pains, a tingling sensation and a feeling of warmth in the left breast and armpit. In the course of therapy these sensations became weaker and disappeared after the fifth injection series.

It can be concluded from the analysis of the over 100 cases treated with ukrain that phenomena such as mentioned arc not side effects but rather an expression of its interaction with the tumor, occurring only in patients who respond to treatment and never in test subjects. They arc further correlated with decrease in intensity and with the retrogression of the tumor itself and therefore important indicators of the effectiveness of therapy. Parallel to the sensations described, in the case of this patient, the tumor became palpably smaller. A mammography carried out in July 1983 still showed the presence of certain mastopathic alterations, although the tumor had largely retrogressed. A mammography made in April 1984 showed no signs of any malignant neoplasm. Today, over a year since the beginning of treatment the patient is clinically healthy. A total remission was obtained.

Case No. 2

In May 1983, a central small-cell bronchial carcinoma with mediastinal lymph nodes was diagnosed in a 75-year-old patient. Combined therapy lasting 6 months was carried out. Six infusions with chemotherapy (endoxin, adriblastin and onkovin) at monthly intervals and during these intervals intravenous injections of ukrain every 3 days were also administered. By November 1983 the tumor had receded as compared with its condition in May 1983. In this immunotherapy it is remarkable how extraordinarily few were the side effects of chemotherapy and how well these were tolerated by the patient. In fact, remarkable successes have been achieved with other patients with parvicellular bronchial carcinoma.

Case No. 3

In July 1983, a 43-year-old male patient had enlarged lymph nodes in the armpit, painful to the touch. Puncture cytology revealed melaniferous cells.

Histological investigation of the operatively removed lymph nodes revealed a 5/6 permeation of the tissue with heavily melaniferous atypical ceils. Diagnosis: metastasis of a probably nodular melanoma. Anamnestically, 2 years previously there existed on the upper right arm a slightly bleeding hemispherical brown-black nodule. On investigation there, were merely signs of tissue changed by scarring, the primary tumor could not be located with certainty. The melanin excretion in the urine was Thormalen positive, so that it could be safely concluded that the patient was in the third stage. Treatment with ukrain was carried out with a total of 5 series of injections. Initially, reactions were again strong. Stabbing pains, feeling of warmth in the region of the armpits, the upper right arm and the back. In the course of therapy these decreased and eventually disappeared. It should be pointed out that, initially, numerous cutaneous areas became visible, which were of varying size, unclearly defined and fluorescent. They likewise decreased in the course of the second and third series of injections d finally disappeared. This allowed a follow-up of therapy. Parallel to this, the melanin excretion was still positive in September 1983. In March 1984 it turned negative for the first time. Further examinations during the following months remained negative. The patient is symptom-free today, and 14 months after establishment of the diagnosis no signs of relapse or metastasis are evident.

As a final word it might be pointed out that these are preliminary results and any conclusive judgement as to their significance is obviously premature. Prospective studies will be carried out using same patient category - ages and treatment comparable.

REFERENCES

¹ Nowicky J. W.: New immuno-stimulating anti-cancer preparation ukrain. 13th International Congress of Chemotherapy, Austria 1983.
² Nowicky J. W.: New immuno-stimulating anti-cancer ration ukrain, 6th International Symposium on Future Trends Chemotherapy, Tirrenia (Pisa), Italy.
³ Nowicky J. W.: Ukrain - Cancer Detection by Meant of Fluorescence. International Symposium on Prevention and Detection of Cancer, Vienna, 1984 (accepted).