Oncotron

Oncotron is an antimetabolite and antitumor substance. This is a cytostatic medicine, an artificial derivative of anthracene.

It is possible that the drug acts by additional electrostatic synthesis of mitoxantrone with DNA, which causes multiple gaps in its chain.

The mitoxantrone component acts on proliferating and non-proliferating cells. Its influence is not tied to the stages of the cell cycle.

In addition to the antitumor effect, mitoxantrone has an antibacterial, immunomodulatory, and with this, antiprotozoal and antiviral effect.

[1]

Indications Oncotron

Used for such disorders:

• non-lymphoblastic leukemia in the acute stage (adults);
• breast carcinoma ;
• having a malignant non-Hodgkin type lymphoma;
• primary hepatic cell carcinoma;
• ovarian carcinoma;
• hormone-resistant prostate cancer, accompanied by pain.

[2], [3], [4]

Release form

The release of the element is made in the form of injection concentrate (i / p or v / v introduction) - inside glass vials with a volume of 10 mg / 5 ml or 20 mg / 10 ml, and in addition, 25 mg / 12.5 ml or 30 mg / 15 ml (equal to the 2nd mg / ml). Inside the box there is 1 such bottle.

Pharmacodynamics

It has not yet been possible to definitively determine the mechanism of antitumor activity, but according to preliminary information it can be concluded that the drug is inserted between the particles of the DNA molecule, thereby blocking the execution of transcription with replication.

At the same time, mitoxantrone slows down topoisomerase-2 and has a nonspecific effect on the cell cycle.

Pharmacokinetics

For intravenous injection, mitoxantrone passes at high speed into the tissues, after which it is distributed there; from there it is subsequently gradually released. Large concentrations of the element are recorded inside the lungs with the liver, and in addition, according to the degree of decrease: inside the bone marrow, heart, thyroid with spleen, pancreas and adrenal glands with kidneys. BBB does not overcome.

Intraplasmic protein synthesis equals 90%; metabolic processes develop inside the liver. During the 5-day period, 13.6-24.8% of the substance is excreted from the body along with the bile, and 5.2.7.7.9% is excreted in the urine. The terminal half-life is 9 days.

In individuals with problems in the liver, a decrease in the rate of elimination of drugs is observed.

Dosing and administration

Mitoxantrone is an integral component of many chemotherapeutic regimens, therefore, during the selection of dosages, regimen and method of administration for each individual case, it is necessary to study the special medical literature.

The drug is administered at a low speed intravenously - at least 5 minutes; can be used through an IV drip for a 15-30 minute period. It is recommended to use Onkotron at a low speed through an infusion tube, and at the same time perform a quick infusion of 5% glucose fluid or 0.9% NaCl.

It is impossible to administer the drug rectally, s / c, intramuscularly or intraarterially.

In total, a maximum of 200 mg / m ^{2 of the} drug substance is allowed.

In NHL, ovarian carcinoma, breast, or liver, monotherapy uses the medication in a 14 mg / m ² dose  1-fold in a 3-week term. In people who have previously undergone chemotherapy, and in addition, when combined with other antitumor substances, the dosage of drugs is reduced to 10-12 mg / m ². In the case of repeated cycles, portions of the drug are selected, taking into account the duration and intensity of the suppression of hematopoietic bone marrow processes.

With a decrease in the number of neutrophils during previous cycles to <1500 or platelet values to <50,000 cells / μl, the dosage of the drug is reduced by 2 mg / m ². If the decrease in the number of neutrophils is <1000, or the level of platelets - <25000 cells / µl, then further portions of drugs are reduced by 4 mg / m ².

In the case of a non-lymphoblastic form of leukemia, to cause remission, the medication is used daily in a portion of 10-12 mg / m ²  - for a 5-day term, until a total portion of 50-60 mg / m ² is obtained. Apply high dosages of the medication (14+ mg / m ² ) can be daily for 3 days.

To treat hormone-resistant prostate carcinoma, a dosage of 12-14 mg / m ², administered 1 time in 21 days, is required. Along with this, small amounts of GCS are used daily (prednisone at a dosage of 10 mg / day or hydrocortisone at 40 mg / day).

During an intrapleural installation (metastases affecting the pleura in case of NHL or carcinoma of the breast), a single dose equals 20-30 mg. Before the procedure, the drug is dissolved in 0.9% NaCl (50 ml). If possible, exudate should be removed from the pleura before starting treatment. It is necessary to warm the dissolved concentrate of Oncotron to the level of body temperature, and then to enter at a low speed (the session lasts 5-10 minutes), without applying effort. The first portion of the drug is delayed inside the pleural cavity for 48 hours. This whole term the patient needs to move - for optimal distribution of the medication inside the pleura.

Upon completion of the specified time interval (48 hours) re-drainage is performed in the area of the pleural cavity. With an effusion volume of less than 0.2 L, the first therapeutic cycle ends. If this figure is more than 0.2 liters, you need to carry out another installation of 30 mg of the substance.

Before performing the re-installation procedure, it is necessary to determine hematological values. The second portion of the drug may remain inside the pleural cavity. With one treatment cycle, a maximum of 60 mg of the component is allowed. With the number of platelets with neutrophils, which is within the normal range, another intrapleural installation can be performed after 1 month. Within the 1st month before and after the procedure, systemic treatment using cytostatic drugs should be avoided.

[6]

Use Oncotron during pregnancy

It is impossible to appoint Onkotron at breastfeeding or pregnancy.

Contraindications

Among the contraindications:

• strong sensitivity associated with migoxantrone or other components of the drug;
• neutrophil count of less than 1500 / μl (except for non-lymphoblastic leukemia therapy).

Caution is required in the following conditions:

• heart disease;
• previous irradiation in the area of the mediastinum;
• suppression of hematopoietic processes;
• severe renal or hepatic impairment;
• AND;
• acute infections with fungal, viral (including shingles and chickenpox) or bacterial etiology (there is a possibility of generalization and the appearance of pronounced complications);
• diseases that carry a high risk of hyperuricemia (nephrolithiasis of a urate nature or gout);
• Persons who have previously used anthracyclines.

Side effects Oncotron

Among the main side effects:

• lesion of hematopoietic function: leukopenia (often appears by the 6th-15th day, with recovery by the 21st day), thrombocyto-, neutro- or erythrocytopenia. Occasionally anemia occurs;
• Digestive disorders: anorexia, obstipation, nausea, diarrhea, loss of appetite, vomiting, severe pain in the peritoneum, stomatitis and bleeding inside the gastrointestinal tract. Increased activity of liver transaminases and disorder of liver function are rarely observed;
• disorders affecting the cardiovascular system: changes in ECG values, arrhythmia with tachycardia, weakening of the left ventricular ejection fraction, myocardial ischemia, and other than this CHF. Toxic damage in the myocardium (for example, CHF) can occur during therapy with the introduction of mitoxantrone, and after months or even years after its completion. The likelihood of cardiotoxic effects increases when a total portion of 140 mg / m ^{2 is} obtained;
• lesions of the respiratory organs: there are reports of the appearance of pneumonitis, which has an interstitial character;
• signs of allergy: rash, decrease in blood pressure, itching or dyspnea, and also anaphylactic symptoms (for example, anaphylaxis) and urticaria;
• local manifestations: the development of phlebitis; in the case of extravasation, burning, swelling, pain and erythema appear, and in addition to this necrosis, which affects nearby tissues. There is information about the acquisition of the veins, in which the drug was injected, as well as the tissues next to them, of an intense blue tint;
• others: systemic weakness, headaches, alopecia, fever, fatigue, non-specific neurological manifestations, back pain, amenorrhea, and menstrual disorder. Occasionally, the nails and epidermis become bluish. Fungal dystrophy, hyperuricemia, or -creatininemia, and, besides, secondary infections, and curable sclera staining in a blue tint, are rarely observed.

[5]

Overdose

Intoxication can lead to potentiation of myelotoxicity, as well as the above-mentioned adverse symptoms.

Dialysis does not work. In case of poisoning, you must carefully monitor the patient and perform symptomatic measures, if necessary. There are no data on the antidote element mitoxantrone.

Interactions with other drugs

With intravenous injection, the drug should not be mixed with other substances (sediment may occur).

The drug enhances the activity of many cytotoxic drugs - for example, methotrexate, cisplatin with vincristine, cytarabine and dacarbazine with cyclophosphamide, and in addition to this 5-fluorouracil.

The combination of Oncotron and other antitumor substances, as well as the use of drugs during irradiation of the mediastinum zone can increase its myeloid and cardiotoxicity.

Introduction together with drugs that block the secretion of tubules (among them, uricosuric anti-gouty substances - sulfinpyrazon), increases the likelihood of nephropathy.

[7], [8], [9]

Storage conditions

Onkotron needs to be kept in the place closed from small children. Liquid can not be frozen. Temperature marks - a maximum of 25 ° C.

Shelf life

Oncotron can be used within a 3-year period from the date of sale of the drug component.

Application for children

There is no confirmed information that the use of medication in pediatrics is effective and safe.

Analogs

Analogues of substances are means Novantron and Mitoksantron.