Health Care Professional Information

Common Name

Celandine

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)

Herb-Drug Interactions

None known

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
  1. Uglyanitsa KN, et al. Ukrain: a novel antitumor drug. Drugs Exp Clin Res 2000;56:347-56.
  2. Colombo ML, Bosisio E. Pharmacological activities of Chelidonium majus L. (papaveracea). Pharmacol Res 1996;33:127-34.
  3. 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.
  4. Danysz A, Kokoschinegg M, Hamler F. Clinical studies of Ukrain in health volunteers (phase I). Drugs Exp Clin Res 1992;18:39-43.
  5. Jagiello-Wojtowicz E, et al. Preliminary pharmacokinetic studies of Ukrain in rats. Drugs Exp Clin Res 1998;24:309-11.
  6. 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.
  7. Ernst E, Schmidt K. Ukrain - a new cancer cure? A systematic review of randomized clinical trials. BMC Cancer 2005; 5(1):69.
  8. 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.
  9. 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.
  10. 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]
  11. 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.

E-mail your questions and comments to aboutherbs@mskcc.org.