Why is not Ukrain approved yet in Austria/EU?
The anti-cancer preparation UKRAIN has Orphan Drug Status for the treatment of pancreatic cancer in the USA and Australia (Enclosure 5). It is the first medicament in the world that accumulates in the cores of cancer cells very quickly after administration and kills only cancer cells while leaving healthy cells undamaged.
Its inventor and patent holder Dr. Wassil Nowicky was nominated for the Nobel Prize for his medicament in 2005 and the Alternative Nobel Prize in 2007.
Nevertheless it has been fought against in Austria for more than 30 years as can also be read in the book "Krebsmittel UKRAIN; Kriminalgeschichte einer Verhinderung" ("Cancer Drug Ukrain; Crime Story of Obstruction") written by Dr. Eleonore Thun-Hohenstein and published by Verlag Molden (Enclosure 6).
On 28.6.1976 application was made to the responsible Austrian authorities for registration of the preparation, which the inventor named after his earlier home country Ukraine, for use with patients who had exhausted all other modes of therapy.
At the time the Austrian authorities established (Enclosure Winkler) that Ukrain is produced from two registered basic substances, Chelidonium Majus-L. alkaloids (Greater Celandine alkaloids), European Pharmacopoeia, 2004, page 1,690 (Enclosure 1) and Thiotepa, US Pharmacopoeia page 1,367 (Enclosure 2). However, during examination by the authorities it was disregarded that both its efficacy was demonstrated and it was 300 times less toxic than its starting substances. The therapeutic index (the ratio between a toxic and a therapeutic dose of a medicine) for Ukrain is 1,250 in contrast to chemotherapeutics whose therapeutic index is between 1.4 and 1.8 which means that an overdose can lead to patients dying. As is known from press reports, patients often die of the consequences of chemotherapy and not of cancer. See the article (in German) in Spiegel No. 41/2004, page 160 "Giftkur ohne Nutzen".
It has only now been discovered that because of the fact that UKRAIN is produced from two approved basic substances it should have immediately received approval automatically in accordance with the laws applicable in 1976 based on the Spezialitätenverordnung (Speciality Regulation) 1947 (Enclosure 4). Therefore on 23 June 1993, Prof. Dr. G. Hitzenberger, member of the Arzneimittelbeirat (Medicine Advisory Board), was surprised that Ukrain had not yet received approval, "Because this substance has again and again been tested in Austria and in fact already since the summer of 1983." (Enclosure Arrouas).
In their research work with the preparation Ukrain Austrian and international scientists have made trail-blazing discoveries:
that Ukrain is only toxic against cancer cells and not against healthy cells (Enclosure 9). This has been proved in various studies in different countries such as Germany, USA, Italy, Mexico and South Africa. Comparative studies of the selective effect of Ukrain have been carried out on a total of 16 cancer cell and 9 normal cell lines. In the dosage range that was toxic for cancer cells it had no damaging effect on healthy cells. This possibly explains why no tissue necrosis occurs with intramuscular administration of Ukrain.
A. Panzer's group from the University of Pretoria, South Africa, found that Ukrain has a selective malignotoxic effect (only against cancer cells) and that it leaves healthy cells undamaged. In addition, the fine mechanism of action of Ukrain was described in this paper for the first time. In 1998 Panzer wrote, in cooperation with the Center for Continuing Education at Tulane University Medical Center: "It is concluded that Ukrain is selectively toxic to malignant cells by causing a metaphase block which is characterised by abnormal chromosomal distribution, and results in the formation of micronuclei and in apoptosis." (Enclosure Panzer). This study aroused the interest of many scientists. In further studies Mexican, German, Russian, Italian and US scientists also confirmed that Ukrain has a selective effect. Approximately ten publications from around the world are dedicated to this subject and doctoral theses have been written on Ukrain at many universities.
In 2000 a new work by Panzer et al. was published which maintains that Ukrain also has a toxic effect against normal cells (Enclosure Panzer). Nobody has been able to confirm this finding but nevertheless opponents of Ukrain have praised this study highly and Austria has used it as a reason for refusing approval (Enclosure Prof. Winkler, Emea).
that Ukrain accumulates predominantly in cancer cells, demonstrated by autofluorescence (Enclosures 10 and 24)
that Ukrain has anti-angiogenetic properties (Enclosure 11) and
because of these properties, that Ukrain brings about encapsulation of the tumour thus facilitating surgery (Enclosure 12).
This research work has not been supported by the Austrian authorities. In Austria doctors who have used Ukrain have even been hounded with fines and disciplinary procedures in order to force them to distance themselves from Ukrain therapy (Enclosure Nowicky, Langer).
The treatment of more than 600 patients is documented in various publications (including approx. 200 in controlled studies, approx. 150 in uncontrolled studies and more than 210 in case reports and first-hand reports). This figure includes 102 patients with colorectal cancer, 190 with pancreatic cancer, 28 with urinary bladder cancer and approx. 100 with breast cancer.
After the effect of Ukrain on cell cultures in the laboratory had been observed and at the same time it was established that its use poses no risk to health, many doctors began to use the preparation in the treatment of malignant melanoma. With one female patient with metastasising malignant melanoma, with melanin already present in her urine and whose chances of survival were only a few months, nine months of therapy with Ukrain achieved such a completely unusual result that on 12.6.1984 Univ. Prof. Dr. Peter Wodniansky, a dermatologist, felt obliged to request the Ministry of Science and Research to carry out a clinical trial on the preparation. Prof. Wodniansky examined the patient several times during the course of nine months Ukrain therapy and was surprised that the patient gave the impression of being healthy and cured (Enclosure Wodniansky). Until today with this diagnosis the disease is almost without exception fatal and constantly shows itself to be resistant to therapy.
Worldwide 160,000 people are diagnosed with melanoma per year and 48,000 die of it. It is known to be one of the most malignant tumours of all. Since Prof. Wodniansky called for Ukrain to be given a clinical trial billions have been collected and spent on cancer research but incomprehensibly not a single cent has been used to test the potential of Ukrain although until now there is no means of helping those affected. In the period from 1984 to 2008 more than 1½ million people throughout the world have died of malignant melanoma (Enclosure, Melanoma).
In a study carried out in Germany 74 prostate cancer patients were treated with Ukrain and local hyperthermia after all conventional methods of treatment (such as surgical intervention, radiation and androgen-ablative therapy) had proven ineffective, a relapse or progress of the disease was registered and no further methods of treatment were available. In 73% of patients a full remission (cure) was achieved, in 22% a partial remission (no tumour growth) and only in 5% was no effect on the tumour achieved. Considering the fact that there are approximately 680,000 new cases annually throughout the world and approximately 220,000 prostate cancer patients die, one is forced to ask: who is really afraid of Ukrain?
It requires clarification why Prof. Ludwig, an expert court witness, who was twice presented with the same medical history of the same person (only the name and date of birth were changed), produced two different reports which totally contradicted one another.
A female patient with a tumour of the large intestine the size of a child's head, which was diagnosed on 17.5.1988, is still alive today without remission after an operation and Ukrain monotherapy. She wanted to claim the costs of Ukrain treatment back from the state health insurance fund. Under Austrian law payment was also designated for unregistered medicaments which preserve human life.
A doctor wrote the appropriate prescription but the state health insurance fund nevertheless refused to take over the costs despite the fact that the patient had always paid her contributions. She therefore decided to seek legal redress. The judge was of course not specialised in the field of medicine so an expert witness, Prof. Ludwig, a leading oncologist, was called upon to provide an opinion. In court he negated the results of therapy and classified the successful outcome as self-healing (Enclosure). For this reason state health insurance fund refused the patient reimbursement of her expenses.
She was shocked in addition, because it must be known to all oncologists that such a tumour can never be cured by self-healing. Also, not one single case of this kind has ever been described in the literature. Because of this Prof. Ludwig was presented with the same medical history once again with a changed name and date of birth. This time he classified the case as completely hopeless:
"Your acquaintance is in a condition after operation on an ulcerating adenocarcinoma of the large intestine, which has already produced lymph node metastases. The size of the primary tumour is striking, the fact that it was already ulcerated and furthermore the bad differentiation. These factors point to an unfavourable prognosis." (Enclosure)
Nevertheless Ms Jakob (Enclosure 18) is still alive today more than twenty years later. This success is no coincidence and also no self-healing but the result of Ukrain therapy. No doctor can point to a similar case with such a sensational result using any other therapy.
In a clinical study carried out by Professor Bondar (Enclosure 19) of Donetsk University, Ukraine, 48 patients suffering from colorectal cancer were randomised: 24 patients received intensive radiotherapy combined with chemotherapy (5-Fluorouracil, 5-FU) before surgery (Group I), and the other 24 patients were treated with Ukrain as monotherapy receiving 10 mg every second day before the operation and a total of 40 mg after the surgical intervention. Afterwards repeated doses of Ukrain were administered over the next 6 months. 14 months later relapses appeared in 2 patients (8.3%) from the Ukrain group and 6 patients (25%) from the group with standard therapy.
In a randomised study carried out by Prof. Susak (Enclosure 20) from the University of Kiev, Ukraine, 96 patients suffering from colorectal cancer were included: 48 patients were treated with Ukrain (15 of them with metastasising and 33 with non-metastasising colorectal tumours) and 48 patients were treated with the chemotherapeuticum 5-FU and radiation. The survival rate after 21 months was 78% in the group treated with Ukrain and 33% in the group treated with 5-FU and radiation.
Who can say how many colorectal cancer patients all over the world could have been helped with Ukrain therapy? Who takes responsibility for so much suffering that could have been prevented with somewhat more commitment and less indifference? However, the product that has been able to help so many people and even save their lives has been made inaccessible to them due to a negative decision by the Austrian Ministry of Health. It should be borne in mind that in Austria alone approx. 5,000 people per year are diagnosed with this type of cancer and 2,500 die (Enclosure 21). Worldwide approx. one million people per year are diagnosed with colorectal cancer and just over half a million die (Enclosure 22).
When the leading world expert on the treatment of pancreatic cancer, Prof. H.G. Beger of the University of Ulm, Germany, author of 21 books and more than 600 scientific publications, was dissatisfied with results so far in the therapy of this very aggressive form of cancer he was in search of new modes of treatment. Prof. Beger turned his attention to the preparation Ukrain and began with laboratory experiments. With in vitro experiments with the pancreatic cancer cell lines Jurkat, MiaPaCa2, AsPC1, BxPC3 and THP-1 the researchers from Prof. Beger's team established that Ukrain has a strong malignotoxic effect on these cell lines. Mitotic analysis found the arrest of cancer cells in the pro and/or metaphase. It was a very important study in clarifying the exact mechanism of action of Ukrain.
After the scientists from the University of Ulm had demonstrated the effectiveness of Ukrain against pancreatic cancer cell lines and defined its mechanism of action, Prof. Beger checked the data on preclinical toxicity, assured himself that the preparation was safe to use, worked out a protocol and applied to the ethics commission and authorities for permission to carry out a clinical pilot study. The Phase II study was financed through the research fund of the University of Ulm. The study medication was partly made available by the producer. There was neutral, external study monitoring and the statistical analysis was carried out by the Biometry Faculty of the University of Ulm.
In this controlled randomised study 90 patients with histologically verified pancreatic cancer were treated. Patients in Group A received the chemotherapeuticum Gemcitabine 1000 mg/m2 body surface, those in Group B received 20 mg Ukrain, and those in Group C received 1000 mg/m2 Gemcitabine followed by 20 mg Ukrain per week. The survival rates after 6 months were 26%, 65% and 74% from Groups A, B and C respectively. The results showed that thanks to therapy with Ukrain in combination with Gemcitabine the survival rates with advanced inoperable pancreatic cancer were doubled.
The concluding evaluation of the study by Priv.Doz. Dr. F. Gansauge on 13 March 2003 stated that the longest survival period in the Gemcitabine group was 19 months, in the group Gemcitabine + Ukrain 26 months and in the Ukrain monotherapy group three patients were still alive 28 months after the beginning of therapy.
The patients were further monitored after the conclusion of the study Gansauge et al, 2002 and it was shown that Ukrain was well tolerated and could also be administered to outpatients without problems. In comparison to Gemcitabine therapy there was a significant prolongation of the survival period in the Ukrain group. The combination therapy of Gemcitabine and Ukrain demonstrated no advantage over Ukrain monotherapy. After these study results the scientists from the University of Ulm recommend Ukrain monotherapy for the palliative treatment of advanced pancreatic cancer.
A recently concluded study by Gansauge et al, 2007 provided additional data on the advantages of combined adjuvant treatment with Ukrain and Gemcitabine. Remission-free survival was 21.7 months and the average survival period was 33.8 months, which is considerably better than the comparable study by Kurosake et al, 2004.
Ukrain has been investigated as neo and adjuvant therapy. In most of the clinical studies Ukrain was administered intravenously at a dose of 10 mg every second day for 20 days, with a total dose of 100 mg/cycle, with a therapy-free interval of 2 – 4 weeks between treatment cycles.
Even in those cases where all possibilities for treatment had already been exhausted with no prospects of further success, with Ukrain complete and/or partial clinical remissions were achieved in several cases. No clinical study is possible with such patient groups.
Ukrain favourably influences a series of laboratory parameters which are regarded as prognostic factors for survival: tumour markers such as CA-125 (ovarian cancer), AFP, MCA and CEA are considerably reduced, CEA by 35% to 75%. Other changes in laboratory parameters that have been observed repeatedly during Ukrain treatment are an increase in the T4/T8 coefficient by 30%, an increase in NK cell activity by 50% and an increase in the number of lymphocytes (by 5 – 15%, especially T-cells, in comparison to the control group).
After treatment with Ukrain a temporary increase in unspecific inflammation parameters can occur, such as ESR and CRP (by approx. 10%). However, after surgical operation these parameters return to normal more quickly and were much lower than in the control groups. This effect is somewhat more pronounced with a higher daily dose.
Ukrain considerably improves the condition of patients, which is evaluated with the so-called Karnofsky Index. These parameters improved by an average of 10 points in the group treated with Ukrain and deteriorated by 5 points in the control group. However, it must be noted that the determination of the Karnofsky Index was not carried out blinded.
Post-operative complications such as prolonged lymph discharge, skin necroses, suppurative inflammation of the operative wounds and lung inflammation were less frequent in patients treated with Ukrain than those in the control groups. This can be seen as a sign of the immunomodulating effect of Ukrain.
All controlled clinical studies have repeatedly shown higher response rates with Ukrain than in the control groups. "Hard criteria" such as the survival rate and/or the number of tumour-free patients is 2 – 3 times higher in the Ukrain group than in the control. Clinical response seems to be more pronounced with longer therapy periods or with a higher number of therapy cycles (such as, for example, in the treatment of urinary bladder carcinomas), as well as with a higher total dosage and/or a longer treatment period. However a clear dose-effect study to establish the best dosage has not yet been carried out. Pre-operative administration of Ukrain improves operability.
206 scientists in 22 countries from 58 universities and research institutes have studied Ukrain and demonstrated its effect. These results have been presented in 274 papers at specialist international congresses and published in 257 publications in the specialist literature (Enclosures 7 and 8).
In the above-mentioned book you can also read that some years ago the Nowicky family was evicted from their flat in winter, under the excuse of disturbance of the peace, with Mrs Nowicky advanced in pregnancy and with a small child. Curiously the family was then accommodated by the very man who was supposed to have felt disturbed. This incident could have triggered a miscarriage with fatal results. In no other country in the world would a court have agreed to the eviction – for Nowicky the laws were simply overridden.
However, this was still not enough for the opponents of Ukrain. The same court ruled that Nowicky should pay a fine of 250,000 euros for the publication of research results (quotations from the specialist literature) on the website www.ukrin.com. These can be read on the Ukrainian website www.ukrain.ua. With this ruling Nowicky was forced to close the website. The intention was to put a stop to the interest shown in Ukrain by many scientists who also wanted to carry out research on the preparation. It is clear to everyone that the internet is the quickest and least problematic network for science. You can check the fact that Nowicky only published research results and no kind of advertising on the Ukrainian website (the preparation is approved in Ukraine).
Several Austrian lawyers were hired to assist with the approval process. The following fact must surely have been known to them: when a product is produced from different approved basic substances it should automatically receive approval. Therefore the Superior Administrative Court (Verwaltungsgerichtshof) also overturned the negative judgement as contrary to the law (Enclosure) and the Human Rights Commission also ruled against Austria (Enclosure). Nevertheless in the constitutional state of Austria it has not so far been possible to gain approval. In the meantime the preparation has received approval in all countries where application has been made including, as mentioned above, Orphan Drug Status in the USA and Australia (Enclosure 5). The fact that approval could not so far be obtained in Austria leads to the supposition that the reasons are connected to the facts contained in the enclosed book "Krebsmittel Ukrain - Kriminalgeschichte einer Verhinderung" by Dr. Eleonore Thun-Hohenstein, published by Molden Verlag, (Enclosure 6). For example, Dr. Jentzsch, a leading civil servant at the Ministry of Health, has expressed himself to the effect that he would retire before Ukrain is granted approval.
It is difficult to understand what aim is being followed. Has this incomprehensible course of action helped the Austrian economy, the Austrian people or cancer patients all over the world? Can cancer patients be helped so much with the pharmaceuticals currently on the market that we can do without a new non-toxic drug? Is this simply ignorance or is there more behind it?
Austrian authorities have not only attempted to prevent scientists working with Ukrain in Austria but also abroad. When I enquired about Ukrain to the responsible authorities the medicament was described as a "dirty drug" (Enclosure). Furthermore the attempt was also made to prevent production (Enclosure Solvay) as well as the procurement of raw materials (Enclosure Thiotepa, alkaloids).
After the Arzneimittelbeirat (Medicine Advisory Board) had approved a broad clinical study of Ukrain, Prof. Pittner imposed conditions: double-blind study with placebo (Enclosure Pittner). No scientist was prepared to carry out a study with cancer patients under such conditions (Enclosure Reintaller).
At the time when Dr. Nowicky came to Austria with the help of Federal Chancellor Dr. Kreisky, he intended to make his product known throughout the world from Austria. For Austria it would have been a fine export product. After 32 years of unavailing struggle for approval he sees himself forced to leave Austria and to send Ukrain throughout the world from other countries.
The inventor has used his time and energy, if not to conquer cancer in the human body, at least to alleviate its damage. However, fighting against cancer in society is not within his power. This struggle must be taken up by others on his behalf.
P.S. I appeal to people all over the world, especially those who have lost a loved one, to support the struggle against the ignorance of a new opportunity to alleviate cancer, because cancer is not a national but an international scourge.
1. Europ. Pharmakopeia
2. Pharmakopeia USA
5. Orphan Drug Status USA und Australien
6. Book "Anticancer Pharmaceutical Ukrain. Criminal Story of a Prevention"
9. Hohenwarter O., Strutzenberger K., Katinger H., Liepins A., Nowicky J.W. Selective inhibition of in vitro cell growth by the anti-tumour drug Ukrain. Drugs Exptl. Clin. Res., XVIII, 1, 1992.
10. Akumuliert krebsgewebe und autofluresyens
11. Congress Rio
13. CV von Prof. Beger
14. Gansauge F., Ramadani M., Beger H.G. Ukrain beim fortgeschrittenen Pankreaskarzinom. Ars Medici 2002, 22, 1056-1062.
15. Gansauge F. Ukrain in Pancreatic cancer: Study Final Report. University Ulm, 2002.
16. Prim. Univ. Prof. Dr. H. Ludwig - Gutachten
17. Prim. Univ. Prof. Dr. H. Ludwig
18. Krankengeschichte Frau Jakob
19. Bondar G.V., Borota A.V., Yakovets Y.I., Zolotukhin S.E. Comparative evaluation of the complex treatment of rectal cancer patients (chemotherapy and X-ray therapy, Ukrain monotherapy). Drugs Exptl. Clin. Res., XXIV (5/6), 1998, 221-226.
20. Susak Y.M., Zemskov V.S., Yaremchuk O.Y., Kravchenko O.B., Yatsyk I.M., Korsh O.B. Comparison of Chemotherapy and X-ray Therapy with Ukrain Monotherapy for Colorectal Cancer. Drugs Exptl. Clin. Res., Vol. XXII (Suppl.), 1996, 43 - 50.
21. Dickdarmkrebs in Oesterreich
22. Dickdarmkrebs in der Welt
23. Nobel Preise
24. Nowicky JW, Greif M, Hamler F, Hiesmayr W, Staub W. Macroscopic UV-Marking through Affinity. Journal of Tumor Marker Oncology, Volume 3, Number 4, 463, 1988.
25a. Univ.-Prof. Dr. med. H. Winkler – Gutachten
25b. Univ.-Prof. Dr. med. H. Winkler - Anlage 1
25c. Univ.-Prof. Dr. med. H. Winkler - Anlage 2
27. Panzer A, Seegers JC. Ukrain, a semisynthetic alkaloid of Chelidonium majus, is selectively toxic to malignant cells by causing a methapase block which results in apoptosis. Proceedings of the American Association for Cancer Research, vol. 39, March 1998, New Orleans, LA, USA.
28. Panzer of normal and malignant cell
29. EMEA – Klagebeantwortung
30. Disziplinarverfahren Nowicky
31. Adolf Langer
32. Letter Wondiansky
33. Malignant melanoma
34. Verwaltungsgerichthof: Zulassung von Ukrain
35. European Court of Human Rights: Case of Nowicky v. Austria
36. E-mail Dr.Stenborg
40. Hofrat Univ.-Doz. Dr. Heribert Pittner
41. Placebo Rheintaler