Health Care Professional Information
Brand Name
Ukrain™ (Nowicky Pharma, Vienna, Austria)
Clinical Summary
A semi-synthetic proprietary product containing alkaloids and Thio-TEPA. Patients use it to treat cancer, HIV/AIDS, and hepatitis C. Ukrain™ is promoted as a selective cytotoxic agent against cancer cells.
Ukrain demonstrated antitumor effects in vitro and in animal studies (9) (10) (11). A systematic review of clinical trials suggests that Ukrain may have potential as an anticancer drug but well designed studies are needed (7). It may prolong survival in pancreatic cancer patients when administered with gemcitabine (8) but large scale studies are needed to confirm this effect.
Reported adverse effects include injection site reactions, slight fever, fatigue, dizziness, nausea, and possibly tumor bleeding.
Ukrain™ is not approved by the Food and Drug Administration but is available in parts of Europe and from Tijuana clinics. Product labeling makes claims of efficacy and safety, which have yet to be proven.
Purported Uses
- Cancer prevention
- Cancer treatment
- Hepatitis
- HIV and AIDS
- Immunostimulation
Constituents
- Alkaloid extract from Chelidonium majus
- Thiophosphoric acid derivatives (triethylene-thiophosphoric acid triamide, Thio-TEPA®)
(1)
Mechanism of Action
Proposed activity 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.
(1) (2) (3)
Pharmacokinetics
Following administration, Ukrain distributes rapidly throughout the body, including the brain and central nervous system. Most of the compound remains unmodified and is excreted through the kidneys. Ukrain administered to rats intraperitoneally at a dose of 28 mg/kg revealed rapid distribution into the plasma and a biologic half-life of approximately 60 minutes. Acute toxicity studies indicate that LD50 dose for intraperitoneally administered Ukrain™ in mice and rats is approximately 280 mg/kg. Maximum tolerated intravenous dose was 3.5 mg/kg in rats and 0.35 mg/kg in rabbits. Chronic toxicity studies in mice and rats with intraperitoneal administration revealed no apparent toxic effects.
(5)
Adverse Reactions
Reported (Parenteral): Soreness at injection site, nausea, diarrhea, dizziness, fatigue, drowsiness, polydipsia, polyuria, and slight fever. Hematological side effects and tumor bleeding were reported in a recent phase II trial.
(1) (4) (6)
Literature Summary and Critique
Gansauge F, et al. NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer: results of a phase II trial. Langenbeck's Arch Surg 2002;386:570-4.
A randomized trial of Ukrain monotherapy versus gemcitabine versus Ukrain plus gemcitabine in patients with unresectable advanced pancreatic cancer. In arm A, 30 patients received 1000 mg gemcitabine/m2 weekly (first cycle: 7 weeks of therapy, 1 week of rest; 2nd-12th cycles: 3 weeks of therapy, 1 week of rest). In arm B, 30 patients received 20 mg Ukrain weekly (following the same cycle). In arm C, 30 patients received both agents at the same doses above. In the first week of the first cycle, arms B and C received 20 mg/day Ukrain. No complete responses were documented. Significantly more partial responses were noted in arms B and C. Median survival according to Kaplan-Meier analysis was in arm A 5.2 months, in arm B 7.9 months, and in arm C 10.4 months. More patients in arms B and C had received prior chemotherapy or radiotherapy. Side effects were comparable between groups, except that arms B and C had more cases of fever, and each had 2 cases of tumor bleeding. Because of this, the authors recommend that Ukrain should only be used under medical supervision.
Dosage (Inside MSKCC Only)
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References
- Uglyanitsa KN, et al. Ukrain: a novel antitumor drug. Drugs Exp Clin Res 2000;56:347-56.
- Colombo ML, Bosisio E. Pharmacological activities of Chelidonium majus L. (papaveracea). Pharmacol Res 1996;33:127-34.
- Panzer A, et al. Ukrain™, a semisynthetic chelidonium majus alkaloid derivative, acts by inhibition of tubulin polymerization in normal and malignant cell lines. Cancer Lett 2000;160:149-57.
- Danysz A, Kokoschinegg M, Hamler F. Clinical studies of Ukrain in health volunteers (phase I). Drugs Exp Clin Res 1992;18:39-43.
- Jagiello-Wojtowicz E, et al. Preliminary pharmacokinetic studies of Ukrain in rats. Drugs Exp Clin Res 1998;24:309-11.
- Gansauge F, et al. NSC-631570 24(Ukrain) in the palliative treatment of pancreatic cancer: results of a phase II trial. Langenbeck's Arch Surg 2002;386:570-4.
- Ernst E, Schmidt K. Ukrain - a new cancer cure? A systematic review of randomized clinical trials. BMC Cancer 2005; 5(1):69.
- Gansauge F, Ramadani M, Schwarz M, et al. The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer. Hepatogastroenterology. 2007 Apr-May;54(75):917-20.
- Skivka LM, Trompak OO, Kudryavets YI, Bezdenezhnykh NA, Susak YM. The effect of NSC-631570 (Ukrain) alone and in combination with pathogen-associated molecules on cell cycle distribution and apoptosis induction of mouse melanoma cells with different biological properties. Exp Oncol. 2010 Jul;32(2):92-6.
- Skivka L, Susak Y, Trompak O, et al. The effect of monotherapy and combined therapy with NSC-631570 (Ukrain) on growth of low- and high-metastasizing B16 melanoma in mice. J Oncol Pharm Pract. 2010 Sep 3. [Epub ahead of print]
- Venkatesh K, Govindaraj S, Ramachandran A, et al. Effect of Ukrain on Cell Survival and Apoptosis in the Androgen-Independent Prostate Cancer Cell Line PC-3. J Environ Pathol Toxicol Oncol. 2011;30(1):11-9.
Consumer Information
How It Works
Bottom Line: Ukrain has not been shown to prevent or treat cancer.
Ukrain is an alkaloid extract from the plant Chelidonium majus. It was developed over 20 years ago by a scientist from the Ukraine, who tested the product on patients with several different types of cancers in the Ukrain and Belarus. In laboratory experiments, Ukrain was found to selectively kill cancer cells while leaving healthy cells alone. Ukrain may kill cancer cells by disrupting the changes in the cell's structure during cell division. Because cancer cells divide more rapidly than healthy cells, such a disruption would slow the growth of cancer cells and causes their death. Some laboratory experiments have suggested that Ukrain causes stimulation of certain aspects of the immune system. However, it is still uncertain if any of these effects occur when Ukrain is used in humans.
Purported Uses
- To prevent and treat cancer
One clinical study showed UkrainTM may prolong survival when used together with gemcitabine in advanced pancreatic cancer. More studies are needed to confirm this effect.
- To treat hepatitis
No scientific evidence supports this use.
- To treat HIV and AIDS
There are no data to back this claim.
- To stimulate the immune system
Although lab studies suggest that UkrainTM stimulates the activity of certain immune cells, human data are lacking.
Research Evidence
Advanced pancreatic cancer:
In this clinical trial, patients were split into three groups. In group A, 30 patients took gemcitabine, a chemotherapy drug; in group B, 30 patients took UkrainTM; in group C, 30 patients took both gemcitabine and UkrainTM. None of the patients had a complete response (disappearance of the tumor), but more of the patients in groups B and C had a partial response (tumor shrinkage) than in group A. Survival was also slightly longer in the patients taking UkrainTM, but because these patients had also received prior chemotherapy or radiotherapy, it is difficult to tell which therapy is responsible for these results. Because of the side effects of UkrainTM, the authors recommend that it should only be used under medical supervision.
Side Effects
- Nausea
- Soreness at injection site
- Dizziness
- Fatigue
- Drowsiness
- Chronic excessive thirst
- Excessive urination
- Slight fever
Special Point
Anecdotes suggest effectiveness in humans, but adequately controlled clinical trials have not been published. Ukrain™ is not approved by the Food and Drug Administration but is available in parts of Europe and from Tijuana clinics. Although the product labeling makes claims of effectiveness and safety, none of these claims have been proven.
Last updated: September 28, 2012
administration (ad-MIH-nih-STRAY-shun)
In medicine, the act of giving a treatment, such as a drug, to a patient. It can also refer to the way it is given, the dose, or how often it is given.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)alkaloid (AL-kuh-loyd)
A member of a large group of substances found in plants and in some fungi. Alkaloids contain nitrogen and can be made in the laboratory. Nicotine, caffeine, codeine, and vincristine are alkaloids. Some alkaloids, such as vincristine, are used to treat cancer.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)analysis (uh-NA-lih-sis)
A process in which anything complex is separated into simple or less complex parts.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)ARMS
A soft tissue tumor that is most common in older children and teenagers. It begins in embryonic muscle cells (cells that develop into muscles in the body). It can occur at many places in the body, but usually occurs in the trunk, arms, or legs. Also called alveolar rhabdomyosarcoma.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)chemotherapy (KEE-moh-THAYR-uh-pee)
Treatment with drugs that kill cancer cells.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)chronic (KRAH-nik)
A disease or condition that persists or progresses over a long period of time.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)clinical (KLIH-nih-kul)
Having to do with the examination and treatment of patients.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)clinical study (KLIH-nih-kul STUH-dee)
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)clinical trial (KLIH-nih-kul TRY-ul)
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)complete response (kum-PLEET reh-SPONTS)
The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)drug (drug)
Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)efficacy (EH-fih-kuh-see)
Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)extract (EK-strakt)
In medicine, a preparation of a substance obtained from plants, animals, or bacteria and used as a drug or in drugs.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)fatigue (fuh-TEEG)
A condition marked by extreme tiredness and inability to function due lack of energy. Fatigue may be acute or chronic.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)fever (FEE-ver)
An increase in body temperature above normal (98.6 degrees F), usually caused by disease.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)Food and Drug Administration (... ad-MIH-nih-STRAY-shun)
An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)gemcitabine (jem-SY-tuh-been)
The active ingredient in a drug that is used to treat pancreatic cancer that is advanced or has spread. It is also used with other drugs to treat breast cancer that has spread, advanced ovarian cancer, and non-small cell lung cancer that is advanced or has spread. It is also being studied in the treatment of other types of cancer. Gemcitabine blocks the cell from making DNA and may kill cancer cells. It is a type of antimetabolite
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)HIV
The cause of acquired immunodeficiency syndrome (AIDS). Also called human immunodeficiency virus.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)immune system (ih-MYOON SIS-tem)
The complex group of organs and cells that defends the body against infections and other diseases.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)injection (in-JEK-shun)
Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)median (MEE-dee-un)
A statistics term. The middle value in a set of measurements.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)nausea (NAW-zee-uh)
A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)pancreatic (PAN-kree-A-tik)
Having to do with the pancreas.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)pancreatic cancer (PAN-kree-A-tik KAN-ser)
A disease in which malignant (cancer) cells are found in the tissues of the pancreas. Also called exocrine cancer.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)partial response (PAR-shul reh-SPONTS)
A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)radiotherapy (RAY-dee-oh-THAYR-uh-pee)
The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiation therapy.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)randomized
Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments.
(http://www.cancer.gov/dictionary)scientist (SY-en-tist)
A person who has studied science, especially one who is active in a particular field of investigation.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)therapy (THAYR-uh-pee)
Treatment.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)tumor (TOO-mer)
An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)unresectable (UN-ree-SEK-tuh-bul)
Unable to be removed with surgery.
Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)
