Oncotron

Oncotron is an antimetabolite and antitumor agent. It is a cytostatic drug, a synthetic derivative of anthracenedione.

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

The component mitoxantrone affects proliferating and non-proliferating cells. Its effect is not tied to the stages of the cell cycle.

In addition to the antitumor effect, mitoxantrone has antibacterial, immunomodulatory, and at the same time antiprotozoal and antiviral effects.

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Indications Oncotron

It is used for the following disorders:

• non-lymphoblastic leukemia in the acute stage (adults);
• breast carcinoma;
• malignant non-Hodgkin's lymphomas;
• primary hepatocellular carcinoma;
• ovarian carcinoma;
• Hormonally resistant prostate cancer accompanied by pain.

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Release form

The element is released in the form of an injection concentrate (intravenous or intrapuncture) - inside glass vials of 10 mg/5 ml or 20 mg/10 ml, and also 25 mg/12.5 ml or 30 mg/15 ml (equal to 2 mg/ml). There is 1 such vial inside the box.

Pharmacodynamics

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

At the same time, mitoxantrone inhibits topoisomerase-2 and has a non-specific effect on the cell cycle.

Pharmacokinetics

When injected intravenously, mitoxantrone passes into tissues at high speed, after which it is distributed there; from there it is gradually released. High concentrations of the element are recorded inside the lungs with the liver, and in addition, in decreasing order: inside the bone marrow, heart, thyroid gland with the spleen, pancreas and adrenal glands with the kidneys. It does not overcome the BBB.

Intraplasmic protein synthesis is 90%; metabolic processes develop inside the liver. Over a 5-day period, 13.6-24.8% of the substance is excreted from the body with bile, and 5.2-7.9% with urine. The terminal half-life is 9 days.

In people with liver problems, the rate of drug elimination is reduced.

Dosing and administration

Mitoxantrone is a component of many chemotherapeutic regimens, so when selecting dosages, regimens and methods of administration for each individual case, it is necessary to study the special medical literature.

The drug is administered at a low rate intravenously - at least 5 minutes; it can be used through a drip - over a 15-30 minute period. It is recommended to use Oncotron at a low rate through an infusion tube, and at the same time perform a rapid infusion of 5% glucose liquid or 0.9% NaCl.

The drug cannot be administered rectally, subcutaneously, intramuscularly or intra-arterially.

In total, a maximum of 200 mg/m2 of the medicinal substance may be ^administered.

In NHL, ovarian, breast or liver carcinoma, the drug is used in monotherapy in a dose of 14 mg/m2 ^once per 3-week period. In people who have previously undergone chemotherapy, and in addition to this, when combined with other antitumor agents, the dosage of the drug is reduced to 10-12 mg/m2 ^. In the case of repeated cycles, the dose of the drug is selected taking into account the duration and intensity of suppression of hematopoietic bone marrow processes.

If the neutrophil count during previous cycles has decreased to <1500 or platelet count to <50,000 cells/μl, the dosage of the drug is reduced by 2 mg/m2 ^. If the neutrophil count has decreased to <1000 or platelet count to <25,000 cells/μl, further doses of the drug are reduced by 4 mg/ ^m2.

In the case of non-lymphoblastic leukemia, to induce remission, the drug is used daily in a dose of 10-12 mg/m2 ^- over a 5-day period, until a total dose of 50-60 mg/m2 is obtained ^. Large doses of the drug (14+ mg/m2 ⁾ can be used daily for 3 days.

To treat hormone-resistant prostate carcinoma, a dosage of 12-14 mg/ ^m2 is required, administered once every 21 days. Along with this, small doses of GCS are used daily (prednisolone at a dosage of 10 mg/day or hydrocortisone - 40 mg/day).

During intrapleural installation (metastases affecting the pleura in the case of NHL or breast carcinoma), a single dose is 20-30 mg. Before the procedure, the drug is dissolved in 0.9% NaCl (50 ml). If possible, exudate from the pleura should be removed before starting treatment. The dissolved Oncotron concentrate must be warmed to body temperature and then administered at low speed (the session lasts 5-10 minutes), without applying force. The first portion of the drug is retained in the pleural cavity for 48 hours. During this entire period, the patient must move - for optimal distribution of the drug in the pleura.

After the specified time period (48 hours) is completed, repeated drainage is performed in the pleural cavity area. If the effusion volume is less than 0.2 l, the first therapeutic cycle ends. If this figure is more than 0.2 l, another installation of 30 mg of the substance must be performed.

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

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Use Oncotron during pregnancy

Oncotron should not be prescribed during breastfeeding or pregnancy.

Contraindications

Among the contraindications:

• severe hypersensitivity to migoxantrone or other components of the drug;
• neutrophil count less than 1500/μl (except for treatment of non-lymphoblastic leukemia).

Caution is required in the following conditions:

• cardiac pathologies;
• previous irradiation in the mediastinal area;
• suppression of hematopoietic processes;
• severe renal or hepatic dysfunction;
• BA;
• acute infections of a fungal, viral (this includes shingles and chickenpox) or bacterial etiology (there is a possibility of generalization and the appearance of severe complications);
• diseases that carry a high risk of developing hyperuricemia (urate nephrolithiasis or gout);
• persons who have previously used anthracyclines.

Side effects Oncotron

Among the main side effects:

• damage to the hematopoietic function: leukopenia (often appears by the 6th-15th day, with recovery by the 21st day), thrombocyto-, neutro- or erythrocytopenia. Anemia occasionally occurs;
• digestive disorders: anorexia, constipation, nausea, diarrhea, loss of appetite, vomiting, severe pain in the peritoneum, stomatitis and bleeding in the gastrointestinal tract. Rarely, increased activity of liver transaminases and liver dysfunction are noted;
• disorders affecting the cardiovascular system: changes in ECG values, arrhythmia with tachycardia, weakening of the left ventricular ejection fraction, myocardial ischemia, and in addition, CHF. Toxic damage to the myocardium (for example, CHF) can occur both during therapy with the introduction of mitoxantrone and months or even years after its completion. The likelihood of developing cardiotoxic effects increases with the receipt of a total dose of 140 mg/ ^m2;
• Respiratory system damage: there are reports of the occurrence of pneumonitis of an interstitial nature;
• signs of allergy: rash, decreased blood pressure, itching or dyspnea, as well as anaphylactic symptoms (eg, anaphylaxis) and urticaria;
• local manifestations: development of phlebitis; in case of extravasation, burning, swelling, pain and erythema appear, as well as necrosis affecting nearby tissues. There is information about the veins in the area where the drug was injected, as well as the tissues next to them, acquiring an intense blue tint;
• others: systemic weakness, headaches, alopecia, increased temperature, severe fatigue, non-specific neurological manifestations, back pain, amenorrhea and menstrual irregularities. Rarely, the nails and epidermis acquire a bluish tint. Nail dystrophy, hyperuricemia or -creatininemia are observed isolated cases, as well as secondary infection and curable blue staining of the sclera.

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Overdose

Intoxication may lead to potentiation of myelotoxicity, as well as the above-mentioned side effects.

Dialysis does not bring results. In case of poisoning, the patient should be closely monitored and symptomatic measures should be taken if necessary. There is no data on the antidote of the element mitoxantrone.

Interactions with other drugs

When administered intravenously, the medicine must not be mixed with other substances (a precipitate may form).

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

The combination of Oncotron and other antitumor agents, as well as the use of drugs against the background of irradiation of the mediastinal area, can increase its myelo- and cardiotoxicity.

Administration together with drugs that block tubular secretion (including uricosuric anti-gout agents – sulfinpyrazone) increases the likelihood of developing nephropathy.

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Storage conditions

Oncotron must be stored in a place closed to small children. The liquid must not be frozen. Temperature marks - maximum 25°C.

Shelf life

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

Application for children

There is no confirmed information that using the drug in pediatrics is effective and safe.

Analogues

Analogues of the substance are Novantrone and Mitoxantrone.