Ukrain

Ukrain (NSC-631570) is claimed to be a semisynthetic compound of thiophosphoric acid (triaziridide) and the alkaloid chelidonine derived from the common weed, Chelidonium majus (greater celandine), which grows primarily in Europe and Asia.1 Ukrain is not a licensed drug in any of the EU countries. Information is lacking regarding the purity of the preparation.

Description of treatment method

Ukrain is most commonly administered intravenously. It is claimed that it consists of one molecule of thiophosphoric acid conjugated to three molecules of chelidonine.

History / providers

Ukrain was developed in 1978 by Dr. Wassil J. Nowicky, director of the Ukrain Anti-Cancer Institute of Vienna, Austria and first presented at the 13th International Congress of Chemotherapy in Vienna in August 1983. In 2004 and 2006, Nowicky was nominated for the Nobel Prize in Chemistry. The manufacturers of Ukrain is Nowicky Pharma, A-1040 Vienna, Austria.

Extracts from Chelidonium majus, a poisonous plant, were traditionally used for liver and gallbladder complaints, loss of appetite and gastroenteritis, although none of these indications are supported by trial evidence. Chelidonium majus contains a range of more than 30 alkaloids, most notably isochinolin derivatives (chelidonine, coptisine, berberin etc.). Chelidonine has antispasmodic, weak central analgesic and papaverine-like effects. Chelidonium majus extracts have been shown to stimulate production of bile and pancreatic digestive enzymes in human studies.2

Thiotepa is a chemotherapy drug and cancer chemotherapeutic member of the alkylating agent group and is derived from aziridine and thiophosphoryl chloride and its main toxicity is myelosuppression.37

Ukrain has been described as a semi-synthetic Chelidonium majus alkaloid derivative, consisting of three chelidonine alkaloids combined to triaziridide. Panzer et al found the actions of Ukrain to be similar to the Chelidonium majus alkaloids it is prepared from.8 Thus, they wanted to assess its chemical integrity. Chemical analyses of Ukrain was inconsistent with the proposed trimeric structure and demonstrated that at least some commercial preparations of Ukrain consist of a mixture of C. majus alkaloids (including chelidonine).

In another study the same team found the antimitotic actions of Ukrain to be reversible in low doses in vitro.30 They suggest that the lack of adverse effects found in vivo may be due to the lack of therapeutically effective dosages being administered, therefore enabling cells to overcome the metaphase arrest and survive.

Serious doubts have been voiced concerning the chemical purity of the allegedly semi-synthetic mixed preparation from alkaloids of Chelidonium majus L and thiotepa.33 No thiotepa was contained in the Ukrain sample they investigated. Nowicky later on also claimed that the free thiotepa is removed out of the compound and that what is left is the Ukrain molecule and parts of the Chelidonium extract.41

Claim of efficacy / mechanisms of action / alleged indication

Several reports describe Eastern European clinical trials using Ukrain for people with various types of cancer.3 These findings cannot be applied to greater celandine because the alkaloids have been modified from their original form. The mechanism of action of Ukrain is unknown whereas the mechanism of action of thiotepa is known. The drug works by damaging the DNA of cells, leaving the cell unable to divide. Without cell division, the tumour cannot grow and spread.

Proposed activity of Ukrain includes cytotoxicity from effects on cellular oxygen consumption, inhibition of DNA, RNA, and protein synthesis, and induction of apoptosis. In vitro studies demonstrate weak inhibition of tubulin polymerization causing arrest at G2/M phase of the cell cycle. Limited in vitro data support the claim that Ukrain has selective cytotoxicity against cancer cells. Ukrain also is promoted for its claimed ability to increase total T-cell count and T-helper lymphocytes, while decreasing T-suppressor cells. In vitro activation of splenic lymphocytes also was reported.6 8 34

Various claims of efficacy of Ukrain exist, which have so far not been backed up by compelling scientific evidence. For instance, the producer of Ukrain claims that:

• It is toxic against cancer cells at the therapeutic dose but not against healthy cells.
• It accumulates at the site of the tumour very rapidly after injection and brings about the encapsulation of larger tumours through anti-angiogenesis, thereby increasing operability.
• It regenerates the immune system.

Antineoplastic and immunomodulatory effects have been suggested. For instance it has been suggested that the alkaloids interfering with the metabolism of cancer cells diminish synthesis of DNA, RNA and proteins. It has also been suggested that cellular oxygen consumption may be inhibited and thus a programmed cell death of malignant cells is thought to be induced.4

Prevalence of use

No data exist to estimate the prevalence of use of Ukrain by cancer patients.

Legal issues

Ukrain has no drug approval in the EU. In the UK, Ukrain neither has a marketing authorisation nor is it registered under the ‘traditional use’ label. It is not FDA-approved in the US but is approved in Mexico, and the United Arab Emirates as a standard anticancer medication. According to the manufacturer, NSC 631570 (=Ukrain) has drug licences in several states of the former Soviet Union (Ukraine, Georgia, Turkmenistan, Belarus/White Russia, Azerbaijan Republic, Tadshikistan, and the Ukraine. Ukrain has also been designated as an Orphan Drug for pancreatic cancer in the USA and in Australia.28

In 2006, Dr Wassil Nowicky submitted a complaint as set out in Article 34, European Convention on Human Rights to the President of the European Court of Human Rights of the European Council regarding a rejection for the application for authorisation of the preparation Ukrain as a cancer therapy.

Costs and expenditures

The costs of Ukrain therapy are high; one course costs €700 for the medication alone, and the total treatment costs have been estimated to be around €3,000 per week.22

For ten injections of 10-20 mg intravenously the total cost of medication itself is approximately $3,500.00 (€2,891). This includes shipping, handling, bank transfer and prescription.