Taxanes in chemotherapy: principles, types, side effects and reviews

Everyone knows radiation therapy and surgery as effective means of combating cancer. But do you know about herbal preparations that effectively cope with oncopathologies? These are the so-called taxanes. In chemotherapy today they are not the last place. In the article you can get acquainted with the discovery of drugs, the principles of their action, indications, contraindications, side effects and other useful information about these drugs.

Taxans: how it all began

The history of taxanes in chemotherapy began in 1958, when the US National Cancer Institute launched a large-scale program to find effective anti-cancer drugs. A huge number of caring American citizens and people from all over the world sent thousands of samples of a wide variety of plants to the organization’s laboratories to test their effect on experimental cancer cells.

After 8 years of such research, a sample of the Pacific yew bark, a shrub of the North American forests, was delivered to the laboratory. Since up to 30 thousand units of plants were received each year, the turn until its study came only in 1971. And the results astounded the researchers - from the yew bark an active antitumor drug paclitaxel was isolated. Is this the beginning of the era of taxanes in chemotherapy?

However, the joy of the researchers was premature - the drug showed a frighteningly high toxic effect on the body. Moreover, only in 2 out of 15 already clinical trials did its effect have a pronounced positive effect. Everything was darkened by the fact that for the production of 1 kg of the drug, processing of almost 7.5 tons of bark of the North American shrub was required.

As a result, the Oncology Institute put up a patent for sale. The company that won the tender first of all found a suitable solvent for the substance - it was a mixture of cremophor (castor oil with alcohol). However, such a tool caused severe allergic effects - they had to be suppressed by the introduction of large doses of hormonal drugs. But, besides cremophor, paclitaxel refused to exist in other solutions.

Docetaxel vs Paclitaxel

The real history of taxanes in chemotherapy began in 1992 - then paclitaxel was approved as a therapeutic drug in the treatment of ovarian cancer. In 1994, the drug was used to treat breast cancer. The manufacturing company was also able to find a new source of raw materials, which allowed to preserve a rare Pacific yew.

At the same time, paclitaxel appeared to have a competitor. A pharmaceutical company from France introduced a similar principle of action, but from the needles of European yew. The new drug, docetaxel, was characterized by a higher concentration in the cell, a more damaging effect on the cancer tumor.

From this stage, competition began between the two taxanes. By the way, taking docetaxel was also fraught with difficulties - the element was highly demanding on the solvent. They were surfactants - surfactants. This abbreviation is more familiar to the reader in cosmetic, perfumery products. A solution of polysorbate and alcohol is hidden under it.

The patient also needed to take anti-allergic hormonal drugs in huge quantities - otherwise he would be at risk of death. However, the advantages of docetaxel over paclitaxel were observed here - the administration took place in an hour instead of 4 hours for the latter.

In clinics, therefore, preference was given to the French drug than the American one. In addition, practice has shown its great effectiveness in the treatment of breast cancer.

Nanotechnology and taxanes

What is the future path of taxane species in chemotherapy? The manufacturers of paclitaxel understood that only the following would help return the first place to their remedy:

• Getting rid of castor solvent. He not only added new side effects, but also prevented the introduction of the active substance into the cell. Therefore, paclitaxel circulated through the bloodstream only in the "arms" of a cremophor.
• Manufacturers also thought about reducing the molecule of the active substance itself. After all, the smaller it is, the easier it is for her to penetrate the cage.
• For the paclitaxel molecule, fast transport was required. It could only be human protein.

It took researchers two decades to translate these tasks into reality. As a result, the so-called nanopaclitaxel, a nanomolecule attached to human albumin, was created. Compared with the previous remedy, the new one several times faster penetrated into the affected cell, more securely fixed there in decent concentration.

The patient no longer needed large doses of hormonal drugs. The introduction of nanopaclitaxel itself did not require special equipment. The process took less than half an hour.

The new drug was named "Abraksan." Here are some clinical indicators of its effectiveness:

• Reduction of the size of the cancer focus - 1/3 of the patients.
• Termination of tumor progression - the 23rd week of administration of the drug.
• Overall survival is 65 weeks.

Another advantage of Abraxan is the absence of such a dangerous consequence of taking docetaxel as neutropenia of the fourth degree. This is the name of the absence in the immune system of the necessary number of neutrophils - leukocytes, designed to protect the body from infections. Without them, sepsis can easily develop, which is why treatment with docetaxel is always combined with the use of a stimulant for the production of neutrophils. And this further worsens the tolerance of taxanes in chemotherapy, and also increases the patient's cost of treatment.

Let’s now separately analyze the modern preparations based on paclitaxel and docetaxel.

Paclitaxel

The instruction for taxane in chemotherapy defines it as a cytostatic drug, which is dispensed strictly according to a doctor’s prescription.

The trade names for the product are as follows:

• Abitaxel.
• Yutaxan.
• Paclitaxel-Teva.
• Mitotax.
• Paxen.
• "Taxacade."
• Sindaxel.
• Taxol.
• Intaxel
• "Paclitaxel-LENS".
• Paclitaxel-Ebeve and others.

The principle of action of drugs

The principle of taxane in chemotherapy is the effect on the process of cancer cell division. Paclitaxel inhibits the normal process of reorganization of the dynamic network of microtubules - special intracellular protein structures that make up the cytoskeleton. And it is very important at the stage of mitosis (indirect cell division) and cytocyte interphase.

Another property of the element: paclitaxel induces the formation of “ligaments” (abnormal accumulations of these microtubules) during the entire cell cycle. This causes the formation of their multiple "stars" during mitosis.

Indications paclitaxel

Based on reviews of the drug, one can judge its high efficiency in the treatment of these diseases:

• Kaposi's sarcoma (malignant tumors of the dermis, skin; pathology was discovered by the Hungarian dermatologist Moritz Kaposi, later named after the researcher). Therapy of the 2nd line of the tumor developing in AIDS patients.
• Mammary cancer. Chemotherapy with taxanes in this disease is an adjuvant treatment of patients with metastases in the lymph nodes that developed after complex standard therapy. This also includes treatment of the 1st line of metastatic cancer, which develops after adjuvant therapy with drugs of the anthracycline group. The third indication is a 2-line therapy, which is indicated after combined chemotherapy with the use of anticancer drugs belonging to the anthracycline series.
• Non-small cell tumor of the lungs. This is a first-line therapy of two types - combined with cisplatin and monotherapy of patients for whom radiation therapy is not required, surgical intervention.
• Ovarian cancer The first type of treatment is first-line therapy in combination with cisplatin for patients with a residual tumor, common metastases after the initial laparotomy. The second type of treatment is 2nd-line therapy in patients with a widespread metastatic ovarian tumor after standard procedures that did not lead to a positive outcome.

Contraindications to the use of the drug

Next, we will talk about the tolerance of taxanes in chemotherapy, side effects. Now it is important to list the contraindications for the administration of paclitaxel:

• Pregnancy.
• Lactation - Breastfeeding.
• Severe neutropenia in a patient with a diagnosed solid tumor (less than 1500 / μl).
• The initial or confirmed neutrophil blood count of less than 1000 / μl in patients with AIDS with Kaposi’s sarcoma during treatment.
• Increased individual sensitivity to paclitaxel, other components of the drug (especially castor oil).

Side effects of taxane chemotherapy

How well tolerated are modern drugs containing paclitaxel? Based on reviews of taxon chemotherapy, the following adverse events can be judged:

• Dermatological reactions. Almost all patients report alopecia. Itching, maculopapular rash, erythema, pain, swelling of the tissues, cellulitis are possible.
• Respiratory reactions are very rare. These include pulmonary fibrosis, interstitial pneumonia, radiation pneumonitis, pulmonary embolism.
• From the urinary tract in patients with Kaposi’s sarcoma, nephrotoxicity of the third or fourth severity can be diagnosed.
• The musculoskeletal system can respond with myalgia and arthralgia. Typically, these symptoms disappear on their own after a few days of drug administration.
• The digestive system most often reacts with vomiting, nausea, mucositis, diarrhea. Perforation and mesenteric artery thrombosis, intestinal acute obstruction, increased alkaline phosphatase and AST are also possible.
• The central nervous system and peripheral nervous system can respond with paresthesia. Isolated cases - severe neuropathy, visual impairment, encephalopathy, ataxia.
• The vascular, cardiac system responds with arterial hypotension / hypertension, changes in the ECG, barricardia, thrombophlebitis, and thrombosis of the vessels of the hands.
• The hematopoietic system responds to the effects of the drug with neutropenia, anemia, and infectious complications.
• Allergy is a side effect of taxation chemotherapy. This is shortness of breath, rash, tachycardia, arterial hypotension or hypertension, hyperemia. Some cases - Quincke's edema, back pain, chills, generalized form of urticaria.

We examined the tolerability, side effects of taxanes in chemotherapy - paclitaxel. Let's move on to the next type of drug.

Docetaxel

Docetaxel is defined as a semi-synthetic cytostatic herbal medicine belonging to the group of taxanes. Obtained by chemical synthesis from natural raw materials - needles of European yew.

Dosage, frequency of administration of the drug, lifestyle, nutrition during chemotherapy with taxanes is prescribed only by the attending physician. The medicine is dispensed from pharmacies only according to his prescription.

The trade names for docetaxel are as follows:

• Docetera.
• Tautax.
• Docetaxel.
• "Taxotere."

The principle of the drug

Docetaxel will contribute to the accumulation of tubulin in the microtubules of the affected cell, and prevent their decay. This interferes with the passage of the mitosis phase of the cell, interfacial processes of its development.

Docetaxel in high concentrations is stored in cells for a long time. In addition, it is quite active against living particles producing p-glycoprotein. The drug has a wide range of activity against transplantable human cancer cells.

Indications for the administration of docetaxel

Indications for the use of this taxane in the treatment of cancer patients are as follows:

• Cancer of the prostate gland is hormone-resistant, metastatic.
• Tumors of the head and neck (squamous, malignant, metastatic) - with the ineffectiveness of previous therapy.
• Therapy of the 2nd line in ovarian cancer - with the failure of treatment of the 1st line.
• Lung cancer - non-small cell metastatic or locally advanced, inoperable. Docetaxel is prescribed for combination therapy of the 1st
• Cancer with breast metastases - with trastuzumab, tumor expression, in the absence of a stage of previous chemotherapy.
• Breast cancer is metastatic and locally advanced.
• Adjuvant treatment for operable breast cancer - with damage to the regional lymph nodes.

Contraindications to the drug

Contraindications to treatment with docetaxel are as follows:

• Pregnancy.
• Lactation stage.
• Impaired liver function. Individual intolerance of the patient to docetaxel or other components of the drug.
• The number of neutrophils in the blood is less than 1500 / μl.

Now we turn to the tolerance of taxane in chemotherapy, side effects of the introduction.

Side effects

Patient reviews, clinical studies show the following negative effect of docetaxel administration:

• The hematopoietic system reacts with reversible neutropenia, which can be accompanied by anemia, fever.
• Speaking of side effects, tolerance of taxanes in chemotherapy, one cannot fail to note an extensive series of allergic reactions to docetaxel: shortness of breath, itching, chest tightness, chills, drug fever. As a rule, this is felt in the first minutes of the drug. Less commonly, erythema, generalized rash, bronchospasm, arterial hypotension.
• The most common dermatological reaction is hair loss (alopecia). Less commonly, a rash with edema, itching, skin erythema, a violation of normal pigmentation.
• The digestive system can respond with diarrhea, anorexia, vomiting, nausea, stomatitis, constipation, taste disturbance, esophagitis, pain in the epigastric region.
• The liver in some cases responds to the administration of the drug by increasing the activity of AST, alkaline phosphatase, ALT, and increasing the level of bilirubin in the patient’s blood.
• The cardiovascular system can be affected in the form of heart failure, angina pectoris, tachycardia, hypertension or hypotension.
• The nervous system reacts with hyperesthesia, dysesthesia, pain, burning sensation, general weakness.
• Other reactions are inflammation, edema of the eyelids, local hemorrhages, phlebitis, ascites, weight gain, pericardial or pleural lung attacks, lacrimation, conjunctivitis, shortness of breath, asthenia, muscle weakness, sepsis, local or generalized pain.

Treatment with taxanes derived from plant materials is one of the methods of chemotherapy in the fight against cancer. However, today it is fraught with a variety of side effects.