Vincristine is a natural molecule isolated for the first time from the plant Catharanthus roseus (or Vinca rosea ), perhaps better known as periwinkle from Madagascar.
Vincristine is used in the treatment of different types of tumors. It is considered a very important drug, so much so that it is included in the list of essential drugs compiled by the World Health Organization (WHO).
Vincristine - Chemical Structure
This list lists all the drugs that must be present within a basic health system.
Indications
For what it uses
The use of vincristine is indicated for the treatment of the following diseases:
- Acute lymphoblastic leukemia;
- Hodgkin's lymphoma;
- lymphosarcoma;
- Reticulosarcoma;
- Rhabdomyosarcoma;
- Neuroblastoma;
- Wilms tumor (a type of kidney cancer);
- Adrenal medullary cancer;
- Ewing's sarcoma (a type of bone cancer);
- Small cell lung cancer;
- Breast cancer;
- Multiple myeloma;
- Retinoblastoma (a type of eye cancer).
Vincristine can be used both as monotherapy and in combination therapy with other anticancer drugs.
Warnings
The administration of vincristine must be carried out under the strict control of doctors specialized in the administration of powerful anticancer agents.
Vincristine should only be administered intravenously, as other routes of administration could also be fatal.
The contact of vincristine with the eyes must be absolutely avoided; if this happens, it is necessary to rinse with plenty of water and contact a doctor.
Caution should be exercised when administering vincristine to patients with pre-existing leukopenia and / or viral infections.
Great care must be taken with the administration of vincristine in patients suffering from pre-existing neuromuscular pathologies, as there may be an increase in the neurological side effects induced by the vincristine itself.
Extravasation of the drug into the tissues can be irritating, so it must be absolutely avoided. If this happens, the application of hot packs could be useful to reduce discomfort and reduce the risk of inflammation of the subcutaneous tissue.
Interactions
Concomitant administration of vincristine and phenytoin (an antiepileptic drug) may cause a reduction in the plasma concentration of phenytoin, thereby reducing its therapeutic efficacy.
Concomitant administration of vincristine and mitomycin (another anticancer medicine) can cause dyspnoea and bronchospasm.
The myelotoxicity (toxicity to bone marrow) of vincristine can be increased by the simultaneous administration of other drugs that inhibit the bone marrow.
The harmful effects of vincristine on the nervous system may be worsened by the concomitant administration of:
- Isoniazid (a drug used to treat tuberculosis);
- Asparaginase (a drug used in the therapy of acute lymphoblastic leukemia);
- Ciclosporina (a drug used in the prevention of rejection in transplants);
- Radiotherapy .
Vincristine may decrease the activity of digoxin (a drug used to increase the strength of cardiac contraction).
Concomitant administration of vincristine and dactinomycin (an anticancer medicine) can cause liver damage.
Concomitant administration of vincristine and bleomycin can cause Raynaud's syndrome (a syndrome that affects peripheral blood vessels, reducing blood flow to the affected areas, such as - for example - fingers and toes or the tip of the nose).
You must inform your doctor if you are taking any kind of medicines, including over-the-counter medications, herbal and / or homeopathic products.
Side effects
Vincristine can induce numerous side effects. However, it is said that the adverse effects do not occur all with the same intensity in each patient, this is because there is a great variability of response to chemotherapy between one individual and another.
The following are the main side effects that may occur following treatment with the drug.
Myelosuppression
Treatment with vincristine may cause myelosuppression (bone marrow suppression). This suppression leads to a reduction in blood cell production (reduced hematopoiesis) which can lead to:
- Anemia (decrease in hemoglobin blood levels), the main symptom of the onset of anemia is the feeling of physical exhaustion ;
- Leukopenia (decreased white blood cell levels), with increased susceptibility to contraction of infections ;
- Plateletopenia (decrease in the number of platelets), this leads to the appearance of bruising and abnormal bleeding with an increased risk of bleeding .
The leukocyte count must be performed before each new drug is given.
Allergic reactions
Vincristine can trigger allergic reactions in sensitive individuals. The symptoms that can occur are skin rash, edema and anaphylaxis .
Alopecia
Vincristine therapy can cause hair and hair loss in general. This is however a temporary side effect. Hair and hair should start growing again shortly after the treatment ends.
Neuromuscular manifestations
Treatment with vincristine can cause neuromuscular disorders that occur following a characteristic sequence. At first only hypoesthesia and paraesthesia occur. Continuing treatment may result in neuritic pain, motor difficulties, loss of deep tendon reflexes, flaccid paralysis of the feet, ataxia and manifestations of the cranial nerves.
In addition, maxillary, pharyngeal, bone, lumbar and muscular pains and parotid pains may also occur.
Finally, cases of seizures associated with hypertension in adults and cases of convulsions followed by coma in children have been reported.
Eye disorders
Cases of transient cortical blindness and optic atrophy with blindness have been reported following the intake of vincristine.
Endocrine manifestations
Vincristine therapy can cause the syndrome of inappropriate secretion of the antidiuretic hormone.
Gastrointestinal disorders
Treatment with vincristine may cause nausea, vomiting and diarrhea . Vomiting can be controlled by the use of anti-emetics (anti-viral drugs), while diarrhea is treated with anti-diarrheal drugs. In any case, it is good to drink a lot to replenish lost fluids.
Vincristine can also cause buccal ulceration, weight loss, abdominal cramps, anorexia, paralytic ileus, constipation, intestinal necrosis with or without perforation.
Kidney and urinary tract disorders
Treatment with vincristine can cause polyuria (excretion of excessive amounts of urine), dysuria (difficulty in excreting urine) and urinary retention caused by bladder atony .
Cardiovascular disorders
Vincristine therapy can cause high blood pressure or arterial hypotension . Cases of coronary heart disease and myocardial infarction have also been reported in patients treated with vincristine and treated - in conjunction - with radiation therapy in the thoracic area.
Lung diseases
Taking vincristine can cause dyspnea and bronchospasm . These symptoms occur especially when vincristine is given in combination with mitomycin. Progressive dyspnea that requires long-term therapy may also occur.
Other side effects
Other side effects that may occur following therapy with vincristine are:
- Difficulty walking;
- Muscular atrophies;
- Temperature;
- Headache.
Overdose
In the event of an vincristine overdose, the symptoms that may occur consist of an aggravation of the drug-induced side effects. There is no antidote, in case you suspect you have taken an overdose of medication you should contact a doctor immediately.
Action mechanism
Vincristine - like all vinca alkaloids - belongs to the class of antimitotic agents. These drugs act during cell division ( mitosis ), in the phase in which the newly synthesized DNA must divide between the two daughter cells. The distribution of the genetic material takes place thanks to the mitotic spindle, a complex structure consisting of microtubules, in turn made up of proteins called tubulins.
Vincristine prevents the tubulin from polymerizing, thus hindering the formation of microtubules and - consequently - also hindering the formation of the mitotic spindle. In this way, the cancer cell is no longer able to complete cell division and undergoes the mechanism of programmed cell death ( apoptosis ).
Mode of Use - Posology
Vincristine is available for intravenous administration. It looks like a powder that must be dissolved in a special solvent just before its use.
The administration can take place in three different ways:
- Through a cannula (a thin tube) that is inserted into a vein of an arm or hand;
- Through a central venous catheter that is inserted subcutaneously into a vein near the clavicle;
- Through the PICC line ( Peripherally Inserted Central Catheter ), in this case, the catheter is inserted into a peripheral vein, usually of an arm. This technique is used for the administration of anticancer drugs for a prolonged time.
The vincristine dosage must be established by the doctor on the basis of the type of tumor to be treated and according to the patient's condition. If vincristine is given in combination therapy, a reduction in the administered dose may be necessary.
In patients with pre-existing liver dysfunction an adjustment of the drug dosage may be necessary.
The following are the vincristine doses that are usually used.
Adults
The usual dose is 1.4 mg / m2 of body surface area, to be administered once a week. The dose can be increased up to a maximum of 2 mg.
children
The usual dose is 1.5-2.0 mg / m2 of body surface area, to be administered once a week.
For children weighing 10 kg or less, the initial dose is 0.05 mg / m2 of body surface area, to be administered once a week.
Pregnancy and breastfeeding
The use of vincristine is not recommended during pregnancy.
Precautions must be taken - by both sexes - to prevent pregnancy, both during treatment with the drug and for a period of at least six months after it ends.
Mothers receiving vincristine should not breast-feed.
Contraindications
The use of vincristine is contraindicated in the following cases:
- Known hypersensitivity to vincristine or to other vinca alkaloids;
- In patients with ongoing bacterial infections;
- In patients with Charcot-Marie-Tooth disease, also known as hereditary motor-sensory neuropathy (an inherited neurological syndrome affecting the peripheral nervous system);
- Pregnant;
- During breastfeeding.
