What is Beromun?
Beromun consists of a powder and a solvent for the preparation of a solution for infusion. Contains the active ingredient tasonermin.
What is Beromun used for?
Beromun is used in patients with soft tissue sarcoma (a type of tumor) of the limbs in combination with melphalan (an anticancer medicine), using a technique called "locoregional limb perfusion" (ILP): both drugs are injected into the limb, while the local blood circulation is kept isolated from the rest of the body. This technique can be used before surgery to reduce the mass of a tumor or to replace the surgery when surgery alone is not sufficient to remove the tumor.
The medicine can only be obtained with a prescription.
How is Beromun used?
Treatment with Beromun should only be performed in specialized centers, by groups of surgeons specialized in the treatment of this type of tumor and in the technique of locoregional limb perfusion. In these centers, intensive care units must always be available, with equipment to continuously monitor the loss of the medicine in the rest of the body, using radioactive tracers.
Before the administration of Beromun it is necessary to isolate the limb: with the patient under general anesthesia, a tight lace is applied upstream of the affected limb, in order to isolate the blood supply and to prevent the medicine from entering the circulation systemic (general). The blood circulation in the limb is then replaced with a "perfusion" of a special liquid and the limb is heated to a temperature between 38 ° and 39 °. Later, Beromun is injected into the perfusion solution at a dose of 3 mg for one arm and 4 mg for a leg, over 90 minutes. Melphalan is administered simultaneously within 60 minutes, after 30 minutes of perfusion of Beromun alone, when the temperature must be increased to 39-40 ° C. The dose of malphalan depends on the size of the arm or leg. At the end of the perfusion (ie after 90 minutes), the medicines are extracted from the limb with the aid of a special washing fluid. Whenever possible (usually after a few weeks) surgical removal of the residual tumor must be performed.
Generally Beromun is used only once. If necessary, a second perfusion can be performed 6-8 weeks after the first treatment. The use of Beromun is not recommended in patients under the age of 18 because there is no information on the safety and efficacy of the product for this age group.
How does Beromun work?
The active substance in Beromun, tasonermin, is a copy of the human protein called tumor necrosis factor alfa1a (TNFα). The precise mechanism of action of TNFα against some types of cancer is not entirely known, but it is believed that it is able to directly eliminate cancer cells and to destroy the blood vessels that supply the tumor mass, stimulating the system immune to attack her. In this way the tumor regresses and its size is reduced, especially if the medicine is associated with other cytotoxic drugs (ie capable of destroying the cells) and if an increase in temperature is induced.
The active ingredient of Beromun, tasonermin, is produced by a method known as "recombinant DNA technology": that is, it is obtained from bacteria in which a gene (DNA) has been introduced that allows them to produce TNFα. Synthetic TNFα acts as the naturally produced protein.
What studies have been carried out on Beromun?
Beromun has been studied in four main studies involving a total of 188 patients, to whom the medicine was given in combination with melphalan. In addition, 62 patients received gamma interferon (another anticancer medicine). A review of the studies carried out by three independent experts showed that only 145 of these subjects were candidates for an amputation or surgical removal of the tumor that would have led to a significant loss of function (disability). Therefore, the main measure of effectiveness was the evaluation of the outcome of the therapy, by experts, for these 145 patients compared to the predictable outcome in case Beromun was not used.
What benefit has Beromun shown during the studies?
Independent experts agreed that 62% of patients treated with Beromun and melphalan (90 out of 145) achieved a better outcome than expected, since it was possible to save the limb without resorting to surgical removal of the tumor or remove the tumor without causing a significant functional loss. The number of patients also treated with interferon gamma was insufficient to establish whether this treatment has further improved or not the therapeutic outcome.
What is the risk associated with Beromun?
Most patients treated with Beromun experience fever, usually mild or moderate. Other very common side effects (seen in more than 1 patient in 10) are infection, cardiac arrhythmia (alteration of the normal heart rhythm), nausea, vomiting, damage to the liver, fatigue, chills, pain in the limb, nerve damage, skin reactions, edema (swelling) and infection at the wound. Some side effects of Beromun are serious and may necessitate the transfer to an intensive care unit after treatment. For the full list of all side effects reported with Beromun, see the Package Leaflet.
Beromun should not be used in people who may be hypersensitive (allergic) to tasonermin or to any of the other ingredients. It must not be administered in patients with serious cardiovascular diseases (affecting the heart and blood vessels), with severe forms of lung pathology, with a recent history of peptic ulcer or with active peptic ulcer, with severe forms of ascites (collection of fluid in the abdominal cavity), with alterations in the blood, with diseases affecting the kidneys or liver, or with hypercalcemia (increase in the amount of calcium in the blood), or in women who are pregnant or breast-feeding. It must also not be given to patients who are contraindicated to use vasopressor drugs (medicines that increase blood pressure), anticoagulants (medicines that make the blood unable to coagulate) or drugs that can damage the heart. . Beromun should not be used in people for whom the use of melphalan is not contraindicated or who cannot undergo an ILP. For further details, please refer to the Summary of Product Characteristics, included in the EPAR.
Why has Beromun been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of Beromun outweigh its risks as an adjunctive therapy to surgical therapy aimed at removing the tumor, in order to prevent or delay amputation of the limb, or as palliative therapy in the presence of inoperable soft tissue sarcomas of the limbs, administered in combination with melphalan for moderate hyperthermic locoregional perfusion of the limb (ILP). The Committee therefore recommended that the product be granted marketing authorization.
More information on Beromun
On 13 April 1999, the European Commission issued a marketing authorization valid throughout the European Union to Boehringer Ingelheim International GmbH for Beromun. The marketing authorization was renewed on 13 April 2004 and 13 April 2009.
The full EPAR for Beromun can be found here
Last update of this summary: 4-2009
