Written by Katja Boehm, Edzard Ernst and the CAM-Cancer Consortium.
Updated February 28, 2017

Ukrain

Does it work?

Controlled trials

There are seven RCTs assessing the efficacy of Ukrain for various cancer types.15 The majority of these studies were published in two different journals between 1995 and 2002 by four different groups of authors, three from the Belarus and one from Germany. They relate to colorectal,16,17 rectal,18 bladder,19 pancreatic,20,21 and breast cancers.22

The results of the six trials carried out in Belarus suggest in all cases that Ukrain is effective in inhibiting cancer progression.16-22 All of these six controlled trials were published with Ukrain manufacturers’ financial involvement. Severe limitations in methodological quality of these trials prevent any firm conclusions and independent replication of the results is needed.

Gansauge et al reported a study of 90 patients with pancreatic cancer treated either with 1000 mg gemcitabine / m2 or 100 mg Ukrain or the combination of both regimens.23 Survival rates suggested that Ukrain was superior to gemcitabine alone. The results and authority of Gansauge et al's study were subsequently questioned.24 The principal investigator, Hans G Beger, a specialist in pancreatic carcinomas was accused of manipulating the outcome of this clinical study in order to push Ukrain on to the market.25 The article also mentions financial sponsorship through the Ukrain manufacturer. Beger denied all accusations.

Uncontrolled trials

In an uncontrolled trial at a German clinic, 203 advanced cancer patients with different types of cancer were treated with Ukrain.26 The authors report surprising remission rates with the highest response rates observed in patients with seminoma and prostate cancer. Some patients were, however, concomitantly treated with regional deep hyperthermia, selenium, cimetidine, thymus extract and vitamin A.

In 2007, Gansauge et al carried out an uncontrolled clinical trial to assess the clinical effects of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in 30 patients with advanced pancreatic cancer.27 The authors report prolonged survival rates with this combination.

Case series

Several case reports exist for the use of Ukrain in cancer patients. Invariably they suggest Ukrain to be effective in terms of antitumour activity, e.g.28-30 However, it must be noted that all case reports were published by the same team of authors.

Pre-clinical studies

While common anticancer drugs are toxic both against cancer and normal cells (cytostatics), Ukrain is allegedly only toxic against cancer cells (“malignocytolytic”). Some studies suggest that there was no evidence to suggest selective cytotoxicity previously reported for Ukrain.3,10 Research carried out at the National Cancer Institute where Ukrain was tested on the screening panel with 60 cell lines from eight human cancer types it was revealed to be cytotoxic against all the solid cancer cell lines tested.31

At least 35 in-vitro and 45 animal experiments have been published that all assess the biological mechanism of Ukrain which suggest that Ukrain has anticancer activity in a wide range of cell lines.15,32-36

Citation

Katja Boehm, Edzard Ernst, CAM-Cancer Consortium. Ukrain [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Ukrain. February 28, 2017.

Document history

Assessed as up to date in February 2017 by Barbara Wider.
Assessed as up to date in January 2015 by Barbara Wider.
Assessed as up to date in August 2013 by Barbara Wider.
Most recent update and revision in May 2012 by Katja Boehm.
Fully revised and updated in July 2009 by Katja Boehm.
Summary first published in November 2005, authored by Katja Boehm and Edzard Ernst.

References

  1. Weiss RF. Herbal Medicine. Gothenburg, Sweden: Ab Arcanum and Beaconsfield, UK: Beaconsfield Publishers Ltd, 1985, 84–8.
  2. Panzer A, Hamel E, Joubert AM, Bianchi PC, Seegers JC. Ukrain (TM), a semisynthetic Chelidonium majus alkaloid derivative, acts by inhibition of tubulin polymerization in normal and malignant cell lines. Cancer Lett 2000;160(2):149-57.
  3. Panzer A, Joubert AM, Eloff JN, Albrecht CF, Erasmus E, Seegers JC. Chemical analyses of Ukrain, a semi-synthetic Chelidonium majus alkaloid derivative, fail to confirm its trimeric structure. Cancer Lett. 2000;160(2):237-41.
  4. van Maanen MJ, Huitema AD, Rodenhuis S, Beijnen JH. "Urinary excretion of thioTEPA and its metabolites in patients treated with high-dose cyclophosphamide, thioTEPA and carboplatin". Anticancer Drugs 2001;12 (6): 519–24.
  5. US 2006/0154947 A1 (2006-06-13) Wassyl Nowicky, Quaternary chelodine and alkaloid derivates, processes for their preparation and their use in manufacture of medicaments. [Patent]
  6. Susak YM, Zemskov VS, Yaremchuk OY, et al. Comparison of chemotherapy and x-ray therapy with Ukrain monotherapy for colorectal cancer. Drugs Exptl Clin Res 1996;22:115–22.
  7. Uglyanitsa KN, Nefyodov LI, Doroshenko YM, Nowicky JW, Volchek IV, Brzosko WJ, Hodysh YJ. Ukrain: a novel antitumour drug. Drugs Exp Clin Res 2000;56:347-56.
  8. Colombo ML, Bosisio E. Pharmacological activities of Chelidonium majus L. (papaveracea). Pharmacol Res 1996;33:127-34.
  9. Jagiello-Wojtowicz E, Kleinrok Z, Urbanska EM. Ukrain (NSC-631570) in experimental and clinical studies: a review. Drugs Exp Clin Res 1998;24:213-9.
  10. Panzer A, Joubert AM, Bianchi PC, Seegers JC. The antimitotic effects of Ukrain, a Chelidonium majus alkaloid derivative, are reversible in vitro. Cancer Lett. 2000;150(1):85-92.
  11. http://www.ukrin.com, accessed 28 February 2017.
  12. http://www.open-cc.com/English/1_04.asp, accessed 28 February 2017.
  13. http://ukrin.com/en/european-court, accessed 28 February 2017.
  14. Hopf G. Ukrain® - Fortschritt oder Rückschritt in der medikamentösen Therapie onkologischer Erkrankungen? Deutsche Zeitschrift für Onkologie 2002;34:31-6.
  15. Ernst E. Schmidt K. Ukrain – a new cancer cure? A systematic review of randomised clinical trials. BMC Cancer 2005;5:69-75.
  16. Susak YM, Yaremchuk OY, Zemskov VS, Kravchenko OB, Liepins A, Yatsyk IM et al. Randomised clinical study of Ukrain on colorectal cancer. Eur J Cancer 1995;31:S153 Abstract 733.
  17. Susak YM, Zemskov SV, Yaremchuk OY, Kravchenko OV, Yatsyk IM, Korsh OB. Comparison of chemotherapy and X-ray therapy with Ukrain monotherapy for colorectal cancer. Drugs Exp Clin Res 1996;22:115-22.
  18. Bondar GV, Borota AV, Yakovets YI, Zolotukhin SE. Comparative evaluation of the complex treatment of rectal cancer patients (chemotherapy and X-ray therapy, Ukrain monotherapy). Drugs Exp Clin Res 1998;24:221-6.
  19. Uglyanitsa KN, Nechiporenko NA, Nefyodov LI, Brzosko WJ. Ukrain therapy of stage T1NOMO bladder cancer patients. Drugs Exp Clin Res 1998;24:227-30.
  20. Zemskov VS, Procopchuk OL, Susak YM, Zemskov SV, Hodysh YY, Zemskova MV. Ukrain (NSC-631570) in the treatment of pancreas cancer. Drugs Exp Clin Res 2000;26:179-90.
  21. Uglyanitsa KN, Nefyodov LI, Brzosko WJ. Comparative evaluation of the efficiency of various Ukrain doses in the combined treatment of breast cancer. Report I. Clinical aspects of Ukrain application. Drugs Exp Clin Res 2000;26:223-30.
  22. Zemskov SV, Prokopchuk O, Susak Y, Zemskov S, Tkachenko O, Hodysh Y et al. Efficacy of Ukrain in the treatment of pancreatic cancer. Langenbecks Arch Surg 2002;387:84-9.
  23. Gansauge F, Ramadani M, Pressmar J, Gansauge S, Muehling B, Stecker K, Cammerer G, Leder G, Beger HG. NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial. Langenbecks Arch Surg 2002;386:570-4.
  24. Arzneimittelbrief. Phase-II-Studie zur Behandlung des fortgeschrittenen, inoperablen Pankreaskarzinoms mit Ukrain. AMB 2002;(5):39a.
  25. Der Spiegel (20. September 2008). Berühmter Chirurg soll wissenschaftliche Studien manipuliert haben. Spiegel 39/2008.
  26. Aschhoff B. Retrospective study of Ukrain treatment in 203 patients with advanced-stage tumors. Drugs Exptl Clin Res 2000;25:249-52.
  27. Gansauge F, Ramadani M, Schwarz M, Beger HG, Lotspeich E, Poch B. The clinical efficacy of adjuvant systemtic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer. Hepato-Gastroenterology 2007;54:917-20.
  28. Prokopchuk OL, Zemskov SV, Susak YM. Ukrain treatment in a patient with metastatic renal cell carcinoma extending to the vena cava inferior. Case report. Drugs Exp Clin Res 2000;26:257-9.
  29. Prokopchuk OL, Zemskov SV, Susak YM. Ukrain treatment of a patient with retroperitoneal synovial sarcoma. Case report. Drugs Exp Clin Res 2000;26:255-6.
  30. Zemskov SV, Prokopchuk OL, Susak YM. Ukrain treatment in a patient with breast carcinoma. Case report. Drugs Exp Clin Res 2000;26:253-4.
  31. http://www.ukrain.ua/enclosures/nci_cell_line.pdf, accessed 28 February 2017.
  32. Habermehl D, Kammerer B, Handrick R, Eldh T, Gruber C, Cordes Net al. Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway. BMC Cancer 2006;6:14.
  33. Cordes N, Plasswilm L, Bamberg M, Rodemann HP. Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation. Int J Radiat Biol 2002;78(1):17-27.
  34. Susak YM, Skivka LM, Rudik MP, Pozur VV, Liubunya AV, Susak YM et al. Comparative investigation of the effect of Ukrain on growth of ascite and solid forms of Ehrlich's carcinoma. Experimental Oncology 2010; 32(2):107-110.
  35. Banerjee A, Pathak S, Biswas SJ, Roy-Karmakar S, Boujedaini N, Belon P et al. Chelidonium majus 30C and 200C in induced hepato-toxicity in rats. Homeopathy: the Journal of the Faculty of Homeopathy 2010; 99(3):167-176.
  36. Funel N, Costa F, Pettinari L, Taddeo A, Sala A, Chiriva-Internati M et al. Ukrain affects pancreas cancer cell phenotype in vitro by targeting MMP-9 and intra-/extracellular SPARC expression. Pancreatology 2010; 10(5):545-552.
  37. Moro PA, Cassetti F, Giugliano G, Falce MT, Mazzanti G, Menniti-Ippolito Fet al. Hepatitis from Greater celandine (Chelidonium majus L.): Review of literature and report of a new case. J Ethnopharmacol 2009;124(2):328-32.
  38. Danysz A, Kokoschinegg M, Hamler F. Clinical studies of Ukrain in healthy volunteers (phase1). Drugs Exp Clin Res 1992;18:39-43.
  39. Stickel F, Seitz HK, Hahn EG, Schuppan D: [Liver toxicity of drugs of plant origin]. Z Gastroenterol 2001; 39(3):225-227.