Avemar

 International Medicine News, July 1. 2006.   by Nansy Walsh 

An extract of fermented wheat germ has shown immunomodulatory effects in vivo and tumor-suppressive effects in vitro. ▸ Studies conducted primarily in Eastern Europe have suggested that the proprietary formulation Avemar may be beneficial in certain types of cancer.test

The Extract and Its Effects An extract of fermented wheat germ, Avemar, was developed during the 1990s by Hungarian biochemist Mate Hidvegi, Ph.D. Initially , Avemar was available as an over the counter dietary supplement, but in 2002 the product was registered as a medical nutriment with an indication for use in cancer treatment by the Hungarian National Institute of Food Safety and Nutrition.“It is not like shark cartilage or cat’s claw or other such products, which may or may not be good,but which are not official cancer treatments. In Hungary , Avemar has become an accepted part of cancer treatment,” Dr. Hidvegi said in an interview. For example, the Hungarian Association of Oral and Maxillofacial Surgeons has issued an official statement indicating that Avemar should be ncluded in the treatment protocol for squamous cell carcinoma of the oral cavity . Avemar is manufactured by Biromedicina Co., Budapest, and is marketed in the United States by American BioSciences Inc., Blauvelt, N.Y. The precise molecular targets by which Avemar produces its immunomodulary effects have not yet been identified, but Dr. Hidvegi and colleagues have proposed several possibilities. Experiments have shown that Avemar inhibits the growth of leukemia cells by inducing apoptosis through activation of the caspase-3–catalyzed cleavage of the poly(ADP-ribose) polymerase (PARP) enzyme. The result of this is that the cells are selectively sensitized to drugs such as 5-fluorouracil (Ann. N.Y.Acad. Sci. 2005;1051:529-42). Avemar also decreases the amount of the major histocompatibility complex class I proteins on tumor cells, which may increase the tumor cells’ exposure to natural killer cells and thereby reduce their metastatic activity (Int. J.Oncol. 2002;20:563-70). It also upregulates the expression of intercellular adhesion molecule1 on tumor-derived endothelial cells and potentiates the effects of tumor necrosis factor–? (Ann. N.Y. Acad. Sci. 2005;1051:515-28). In vivo immunomodulatory effects of Avemar were seen in experiments on mice showing that the compound increased the degree of blastic transformation of peripheral blood T lymphocytes stimulated by the mitogen concanavalin A. In other animal studies, immunocompromised mice that had undergone thymectomy showed improved immune function by not rejecting skin grafts when treated with the extract (Immunopharmacology 1999;41:183-6).

At baseline, control patients were older, but disease stage was worse in the Avemar group; 27.3% of patients in the treatment group had stage IV metastatic cancer, compared with only 3.8% of those in the control group. The Avemar cohort also had a longer time lag from diagnosis to the start of  therapy and less previous radiotherapy . The treatment consisted of 9 mg of  Avemar dissolved in 150 mL of water once daily . The end-point analysis, with follow-up extending to 70 months, showed that progression-related events including new recurrent disease, new metastases, and deaths occurred significantly more frequently in the control group. A total of 16.7% of patients in the Avemar group experienced any progression related event, compared with 42.3% of those in the control group (Br. J. Cancer 2003;89:465-9). No serious adverse events were associated with the treatment. The most common side effects were gastrointestinal disturbances. Avemar also has been evaluated in patients with stage III melanoma by a group of Russian investigators. In their presentation at a 2002 congress of the International Union Against Cancer in Oslo, Norway , Avemar was linked to benefits in terms of progression-free survival in a group of postsurgical patients. A total of 46 patients received dacarbazine, 400 mg/m body surface in cycles of 5 consecutive days, repeated monthly for up to 4 months or until disease progression. In this group, 22 received 9 g Avemar daily during treatment and for 12 months afterward. At 12 months, 75% of the control group had experienced disease progression, compared with 36.3% of the Avemar group. “We now have 3-year follow-up data, again showing statistically significant benefits in progression-free survival and overall survival for the Avemar patients,” said Dr. Hidvegi, who is honorary professor at the Budapest University of Technology and Economics as well as at the Jewish University in Budapest, and is now chairman of Biromedicina. Another pilot study evaluated the effects of the wheat germ extract on chemotherapy-induced febrile neutropenia in a group of 22 children with a variety of solid tumors. All patients received standard chemotherapy , and half also 2 received Avemar, 6 g/m twice daily . Evaluations took place at baseline, at the end of the first month, and every 3 months thereafter. “The chemotherapy protocol used for children with solid tumors is high dose and very myelosuppressive, so although these cancers are 100% curable, the patients are susceptible to infections and some even die,” Dr. Hidvegi said. A total of 30 episodes of febrile neutropenia occurred in the active treatment group during a total of 121 cycles of chemotherapy (24.8%), whereas 46 episodes occurred during the 106 cycles (43.4%) completed by patients in the control group, a difference that was statistically significant ( J. Pediatr. Hematol. Oncol. 2004;26: 631-5). The study showed that Avemar was useful for ameliorating the serious side effects of chemotherapy , Dr. Hidvegi said.