Bestatin Capsules 10 mg for acute non-lymphocytic leukemia in remission (ubenimex)

Are Bestatin Capsules 10 mg effective for acute non-lymphocytic leukemia in remission (ubenimex)?

What are Bestatin Capsules 10 mg?

Bestatin Capsules 10 mg are a prescription medicine for adults with acute non-lymphocytic leukemia. Each white hard capsule (size 3) holds white powder containing 10 mg of ubenimex, the generic name of bestatin. The medicine has been available in Japan since 1987, and it is classified as an antineoplastic agent. It is not a stand-alone treatment. It is added to maintenance and intensification chemotherapy after a complete remission has been reached, with the aim of prolonging survival.

What is acute non-lymphocytic leukemia, and why is treatment continued after remission?

Acute non-lymphocytic leukemia, which includes acute myeloid leukemia, is a cancer of the blood-forming cells in which immature white blood cells multiply uncontrollably. The first stage of treatment aims at complete remission, when leukemia cells can no longer be detected in the bone marrow. Remission does not mean the disease is gone for good, so chemotherapy continues in a maintenance and intensification phase to keep the leukemia from returning. Ubenimex is used during this phase.

How does ubenimex work?

Bestatin was discovered in Japan and described in Umezawa et al., “Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes,” The Journal of Antibiotics, 1976. The way it works against leukemia is not fully established, but the evidence points to the immune system. In tumor-bearing mice, bestatin activated macrophages from the abdominal cavity, spleen cells and natural killer cells, and tumor growth was suppressed. It also binds, through aminopeptidase enzymes, to the surface of immune cells. The leading explanation is that ubenimex strengthens the body’s anti-tumor immunity.

Laboratory work shows further effects:

• In cell cultures, it inhibited the growth of human leukemia and lymphoma cell lines (K562, HL-60 and U-937).
• In animal models, it suppressed tumor growth and metastasis and prolonged survival, alone and with other anticancer agents such as cisplatin and bleomycin.
• In human cells in vitro, it enhanced bone marrow cell function, release of interleukins 1 and 2, lymphocyte activation and macrophage function.

In humans, a single oral dose reaches its peak blood level after about an hour. The blood level has almost disappeared by 24 hours. Most of the drug leaves the body in the urine, two-thirds to three-quarters of it unchanged.

What clinical studies show

The main evidence comes from a randomized controlled trial reported in Ota et al., “Immunotherapy with bestatin for acute nonlymphocytic leukemia in adults,” Cancer Immunology, Immunotherapy, 1986. It was a cooperative trial in Japan, with 115 patients registered and 101 evaluated: 48 received bestatin together with maintenance chemotherapy and 53 received chemotherapy alone. Patients in the bestatin group survived significantly longer. Median survival was 33.3 months, against 18.9 months in the control group, about 1.8 times longer. A follow-up survey extended by about 15 months showed much the same result.

The authors also analyzed results by age. In patients aged 50 to 65, bestatin significantly prolonged both the duration of remission and survival. The bestatin group also tended to achieve a higher rate of second remission in patients whose leukemia had recurred.

Package details: 100 capsules

Active components: ubenimex 10 mg per capsule

Therapeutic effect: Activates anti-tumor immunity, including macrophages and natural killer cells. Taken together with maintenance and intensification chemotherapy after complete remission in adult acute non-lymphocytic leukemia, it prolongs survival.

Dosage and administration: The usual adult dose is 30 mg of ubenimex once daily by mouth. With the 10 mg capsule, this is three capsules a day. Use it together with maintenance and intensification chemotherapy, after complete remission has been induced. The dose may be adjusted according to age and symptoms. The dosage can be adjusted by your doctor.

Contraindications and precautions: The prescribing information lists no specific contraindications. Use in pregnancy only if the benefit outweighs the risk, because impaired fetal growth was reported in rats. Breastfeeding is best avoided, as the medicine passed into milk in rats. No clinical trials have been done in children. In elderly patients, physiological function is often reduced, so treatment proceeds with care.